A study to evaluate the safety of Rosuvastatin in Children and Adolescents with Homozygous Familial Hypercholesterolemia

Study identifier:D356NC00001

ClinicalTrials.gov identifier:NCT02434497

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An Open-Label Long-Term Extension to the Randomized, Double-blind, Placebo-controlled, Multi-center, Cross-over Study of Rosuvastatin in Children and Adolescents (aged 6 to <18 years) with Homozygous Familial Hypercholesterolemia (HoFH)

Medical condition

Homozygous Familial Hypercholesterolemia (HoFH)

Phase

Phase 3

Healthy volunteers

Study drug

Rosuvastatin 20mg

Sex

All

Actual Enrollment

Study type

Interventional

Age

6 Years - 18 Years

Date

Study Start Date: 06 Jun 2015

Primary Completion Date: 17 Nov 2016

Study Completion Date: 17 Nov 2016

Study design

Allocation: N/A
Endpoint Classification: Safety/Efficacy
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Prior to any study related procedures being performed, provision of written informed consent from a parent/both parents or guardian and statement of assent from the child or adolescent (if required by Institutional Review Board [IRB] or Independent Ethics Committee [IEC] according to local regulations and guidelines). Study D3561C00004 participants who have had their 18th birthday (adults) will be required to provide written informed consent. Communication should take place between the Investigator, patient/guardian and child/adolescent to confirm understanding and required compliance with the requirements of the study.
2. Male and female children and adolescents who were aged 6 to <18 years at the onset of Study D3561C00004 (even if they had their 18th birthday during that study) with:
- Documentation of genetic testing confirming 2 mutated alleles of the LDL receptor gene locus; and/or
- Documented untreated LDL C >500 mg/dL (12.9 mmol/L) and TG <400 mg/dL (4.5 mmol/L) and at least 1 of the following criteria:
o Tendinous and/or cutaneous xanthoma prior to 10 years of age; or
o Documentation of HeFH in both parents by:
- genetic and/or
- clinical criteria
3. Negative pregnancy test (b human chorionic gonadotropin analysis) prior to baseline in females of child bearing potential:
- Female patients of child bearing potential must adhere to a pregnancy prevention method (abstinence, chemical, or mechanical) during the study and 3 months following the last dose;
- Male patients should refrain from fathering a child (including sperm donation) during the study and up to 3 months following the last dose; and
4. Were taking study drug at the end of Study D3561C00004 and are willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.

Exclusion Criteria

1. History of statin inducted myopathy or serious hypersensitivity reaction to other HMG CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1 of Study D3561C00004.
2. Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% during Study D3561C00004 or patients with a history of diabetic ketoacidosis within the past year.
3. Uncontrolled hypothyroidism defined as thyroid stimulating hormone >1.5 times the upper limit of normal (ULN) at any time during Study D3561C00004.
4. Evidence of active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert’s disease) as defined as non-transient elevations of ALT or AST elevations ≥3 times the ULN or non-transient total bilirubin ≥2 times the ULN during the Study D3561C00004.
5. Definite or suspected personal history or family history of clinically significant adverse drug reactions (ADRs), or hypersensitivity to drugs with a similar chemical structure to rosuvastatin as well as other statins.

Location

Research Site

Brussels (Woluwé-St-Lambert), Belgium, 1200

Location

Research Site

Copenhagen, Denmark, DK-2100

Location

Research Site

Kubang Kerian, Malaysia, 16150

Location

Research Site

Chicoutimi, QC, Canada, G7H 7K9

Location

Research Site

Halfa, Israel, 31096

Location

Research Site

Taipei City, Taiwan, Province of China, 11217

Arms	Assigned Interventions
Experimental: Single Arm One treatment period for all patients (<1 year and 10 months), with the possibility to up-titrate dose to 40 mg of rosuvastatin for non-Asian patients.	Drug: Rosuvastatin 20mg Active drug 1 or 2 tablets will be taken taken orally, QD, either in the morning or in the evening

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The nine (9) patients recruited were all participants in the D3561C00004 HYDRA study (NCT02226198) four came from Sequence A and five from Sequence B

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Overall	All patients

Participant Flow: Overall Study

	Overall
STARTED	9
COMPLETED	4
NOT COMPLETED	5

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Overall	All patients

Baseline Measures

	Overall
Number of Participants [units: Participants]	9
Age Continuous [units: years] Mean ± Standard Deviation	10.6 ± 2.83
Gender, Male/Female [units: ]
Female	4
Male	5

Outcome Measures

1. Primary Outcome Measure: The number of participants who experianced adverse events and Serious Adverse Events [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	The number of participants who experianced adverse events and Serious Adverse Events
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
The number of participants who experianced adverse events and Serious Adverse Events [units: participants]	5

No statistical analysis provided for The number of participants who experianced adverse events and Serious Adverse Events

2. Primary Outcome Measure: Safety and tolerability in terms of number of participants who had adverse events, Discontinuations due to Adverse Events [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of number of participants who had adverse events, Discontinuations due to Adverse Events
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Safety and tolerability in terms of number of participants who had adverse events, Discontinuations due to Adverse Events [units: participants]	0

No statistical analysis provided for Safety and tolerability in terms of number of participants who had adverse events, Discontinuations due to Adverse Events

3. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN) [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN)
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN) [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	1	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN)

4. Primary Outcome Measure: Safety and tolerability in terms of growth, height [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of growth, height
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of growth, height [units: cm] Mean (Standard Deviation)
Baseline	142.5 (23.57)	136.8 (15.02)
Week 6	143.5 (23.57)	136.8 (15.32)
Week 12	144.0 (23.90)	137.6 (14.94)
Week 18	145.3 (23.56)	138.0 (14.83)
Week 24	145.8 (24.02)	139.2 (15.74)
Week 36	147.0 (24.15)	140.6 (15.61)
Week 48	148.8 (24.25)	142.2 (15.21)
Week 60	158.0 (19.47)	144.0 (16.37)
Week 72	159.0 (20.22)	145.0 (15.12)
Week 84	159.7 (20.43)	148.3 (17.27)
Week 96	165.0 (25.46)	138.0 (12.73)

No statistical analysis provided for Safety and tolerability in terms of growth, height

5. Primary Outcome Measure: Safety and tolerability in terms of abnormalitites in sexual maturation [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormalitites in sexual maturation
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Safety and tolerability in terms of abnormalitites in sexual maturation [units: participants]	0

No statistical analysis provided for Safety and tolerability in terms of abnormalitites in sexual maturation

6. Primary Outcome Measure: Safety and tolerability in terms of growth, height SD-score (or z-score) [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of growth, height SD-score (or z-score)
Measure Description	Height z-score is a dimensionless quantity derived by subtracting the population mean from the individual raw score, and then deviding the difference by the pouulation SD of the reference population. This indicates how many SDs and observation is above or below the general population mean.
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of growth, height SD-score (or z-score) [units: standard deviations] Mean (Standard Deviation)
Baseline	-0.43 (2.025)	-1.05 (1.787)
Week 6	-0.48 (1.911)	-1.05 (1.871)
Week 12	-0.41 (1.975)	-1.19 (1.709)
Week 18	-0.43 (1.610)	-1.14 (1.705)
Week 24	-0.60 (1.730)	-0.96 (1.670)
Week 36	-0.43 (1.836)	-0.76 (1.727)
Week 48	-0.16 (1.781)	-0.72 (1.729)
Week 60	0.05 (1.757)	-1.04 (1.604)
Week 72	0.00 (1.635)	-0.87 (1.604)
Week 84	0.08 (1.734)	-0.33 (1.627)
Week 96	1.18 (0.436)	-0.51 (0.886)

No statistical analysis provided for Safety and tolerability in terms of growth, height SD-score (or z-score)

7. Primary Outcome Measure: Safety and tolerability in terms of growth, weight [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of growth, weight
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of growth, weight [units: kg] Mean (Standard Deviation)
Baseline	36.25 (14.719)	37.42 (16.089)
Week 6	37.20 (16.230)	38.02 (16.700)
Week 12	37.93 (17.110)	38.16 (17.501)
Week 18	38.85 (17.633)	38.40 (16.688)
Week 24	39.15 (17.521)	39.00 (16.704)
Week 36	39.98 (18.293)	39.88 (15.015)
Week 48	41.00 (17.579)	41.16 (16.045)
Week 60	48.47 (16.933)	41.80 (15.656)
Week 72	48.43 (16.393)	42.10 (17.047)
Week 84	50.17 (16.737)	45.28 (19.143)
Week 96	57.35 (16.476)	33.55 (2.192)

No statistical analysis provided for Safety and tolerability in terms of growth, weight

8. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Alanine Aminotransferase (U/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Alanine Aminotransferase (U/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Alanine Aminotransferase (U/L) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	1
Week 18	0	1
Week 24	0	0
Week 36	0	1
Week 48	0	1
Week 60	0	1
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Alanine Aminotransferase (U/L) >ULN

9. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Albumin (g/dL) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Albumin (g/dL) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Albumin (g/dL) >ULN [units: participants]
Baseline	0	1
Week 6	0	0
Week 12	0	0
Week 18	0	1
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Albumin (g/dL) >ULN

10. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Aspartate Aminotransferase (U/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Aspartate Aminotransferase (U/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Aspartate Aminotransferase (U/L) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	1
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Aspartate Aminotransferase (U/L) >ULN

11. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) <LLN [units: participants]
Baseline	0	0
Week 6	0	1
Week 12	1	1
Week 18	0	1
Week 24	1	1
Week 36	1	2
Week 48	1	1
Week 60	1	3
Week 72	2	1
Week 84	1	1
Week 96	0	1

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) <LLN

12. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Bicarbonate (mol/L) >ULN

13. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN [units: participants]
Baseline	2	3
Week 6	0	2
Week 12	2	2
Week 18	1	2
Week 24	2	3
Week 36	1	3
Week 48	1	4
Week 60	1	4
Week 72	2	3
Week 84	2	3
Week 96	0	1

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN

14. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB (pg) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB (pg) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB (pg) <LLN [units: participants]
Baseline	1	3
Week 6	1	2
Week 12	1	2
Week 18	1	2
Week 24	1	2
Week 36	1	2
Week 48	1	3
Week 60	0	3
Week 72	0	3
Week 84	0	3
Week 96	2	1

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular HGB (pg) <LLN

15. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) <LLN [units: participants]
Baseline	1	2
Week 6	1	2
Week 12	1	2
Week 18	1	2
Week 24	1	2
Week 36	1	2
Week 48	1	2
Week 60	0	2
Week 72	0	3
Week 84	0	3
Week 96	2	1

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) <LLN

16. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	0
Week 84	1	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Ery. Mean Corpuscular Volume (fL) >ULN

17. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) <LLN [units: participants]
Baseline	1	0
Week 6	0	0
Week 12	0	1
Week 18	0	1
Week 24	0	0
Week 36	0	1
Week 48	0	0
Week 60	0	0
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) <LLN

18. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) >ULN [units: participants]
Baseline	0	1
Week 6	0	0
Week 12	0	1
Week 18	0	0
Week 24	1	2
Week 36	0	2
Week 48	0	1
Week 60	0	1
Week 72	0	2
Week 84	0	1
Week 96	0	1

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Erythrocytes (10^12/L) >ULN

19. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Hematocrit (%) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Hematocrit (%) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Hematocrit (%) <LLN [units: participants]
Baseline	2	2
Week 6	2	3
Week 12	1	2
Week 18	1	3
Week 24	0	1
Week 36	1	1
Week 48	0	2
Week 60	0	2
Week 72	0	1
Week 84	0	1
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Hematocrit (%) <LLN

20. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Hemoglobin (g/dL) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Hemoglobin (g/dL) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Hemoglobin (g/dL) <LLN [units: participants]
Baseline	2	3
Week 6	2	3
Week 12	1	3
Week 18	1	3
Week 24	0	2
Week 36	1	3
Week 48	1	3
Week 60	0	3
Week 72	0	3
Week 84	0	3
Week 96	0	1

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Hemoglobin (g/dL) <LLN

21. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Leukocytes >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Leukocytes >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Leukocytes >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	1
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Leukocytes >ULN

22. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) <LLN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	1
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) <LLN

23. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) >ULN [units: participants]
Baseline	0	1
Week 6	0	1
Week 12	0	1
Week 18	0	1
Week 24	0	1
Week 36	0	1
Week 48	0	1
Week 60	0	1
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Lymphocytes/Leukocytes (%) >ULN

24. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Monocytes/Leukocytes (%) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Monocytes/Leukocytes (%) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Monocytes/Leukocytes (%) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	1
Week 48	0	0
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Monocytes/Leukocytes (%) >ULN

25. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Platelets (10^9/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Platelets (10^9/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Platelets (10^9/L) >ULN [units: participants]
Baseline	1	0
Week 6	0	1
Week 12	0	0
Week 18	0	0
Week 24	0	1
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Platelets (10^9/L) >ULN

26. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Blood Urea Nitrogen (mg/dL) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Blood Urea Nitrogen (mg/dL) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Blood Urea Nitrogen (mg/dL) <LLN [units: participants]
Baseline	1	0
Week 6	1	0
Week 12	1	0
Week 18	1	0
Week 24	0	0
Week 36	0	1
Week 48	1	0
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Blood Urea Nitrogen (mg/dL) <LLN

27. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Chloride (mmol/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Chloride (mmol/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Chloride (mmol/L) >ULN [units: participants]
Baseline	0	1
Week 6	0	1
Week 12	0	0
Week 18	0	1
Week 24	0	0
Week 36	0	1
Week 48	0	0
Week 60	0	1
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Chloride (mmol/L) >ULN

28. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Creatine Kinase (U/L) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Creatine Kinase (U/L) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Creatine Kinase (U/L) >ULN [units: participants]
Baseline	0	0
Week 6	1	0
Week 12	0	0
Week 18	0	0
Week 24	1	0
Week 36	1	0
Week 48	0	0
Week 60	1	0
Week 72	0	0
Week 84	0	0
Week 96	1	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Creatine Kinase (U/L) >ULN

29. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Glucose (mg/dL) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Glucose (mg/dL) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Glucose (mg/dL) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	1
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	0
Week 84	0	1
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Glucose (mg/dL) >ULN

30. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Lactate Dehydrogenase (U/L) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Lactate Dehydrogenase (U/L) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Lactate Dehydrogenase (U/L) <LLN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Lactate Dehydrogenase (U/L) <LLN

31. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Phosphate (mg/dL) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Phosphate (mg/dL) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Phosphate (mg/dL) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	1
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	1
Week 84	0	1
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Phosphate (mg/dL) >ULN

32. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Protein (g/dL) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Protein (g/dL) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Protein (g/dL) >ULN [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	1
Week 18	0	0
Week 24	0	1
Week 36	1	0
Week 48	0	0
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Protein (g/dL) >ULN

33. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Sodium (mmol/L) <LLN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Sodium (mmol/L) <LLN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Sodium (mmol/L) <LLN [units: participants]
Baseline	2	0
Week 6	1	0
Week 12	0	0
Week 18	3	1
Week 24	0	1
Week 36	0	0
Week 48	0	1
Week 60	0	0
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Sodium (mmol/L) <LLN

34. Primary Outcome Measure: Safety and tolerability in terms of abnormal serum laboratory values, Urate (mg/dL) >ULN [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal serum laboratory values, Urate (mg/dL) >ULN
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal serum laboratory values, Urate (mg/dL) >ULN [units: participants]
Baseline	1	0
Week 6	1	1
Week 12	1	0
Week 18	1	1
Week 24	1	1
Week 36	1	1
Week 48	1	1
Week 60	1	1
Week 72	1	1
Week 84	1	1
Week 96	1	0

No statistical analysis provided for Safety and tolerability in terms of abnormal serum laboratory values, Urate (mg/dL) >ULN

35. Primary Outcome Measure: Safety and tolerability in terms of abnormal urine laboratory values, Urine Ketones [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal urine laboratory values, Urine Ketones
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal urine laboratory values, Urine Ketones [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	1
Week 24	0	0
Week 36	0	0
Week 48	0	1
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	1	0

No statistical analysis provided for Safety and tolerability in terms of abnormal urine laboratory values, Urine Ketones

36. Primary Outcome Measure: Safety and tolerability in terms of abnormal urine laboratory values, Urine Occult Blood [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal urine laboratory values, Urine Occult Blood
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal urine laboratory values, Urine Occult Blood [units: participants]
Baseline	1	1
Week 6	2	1
Week 12	1	2
Week 18	1	1
Week 24	1	1
Week 36	1	1
Week 48	1	1
Week 60	1	1
Week 72	2	1
Week 84	1	1
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal urine laboratory values, Urine Occult Blood

37. Primary Outcome Measure: Safety and tolerability in terms of abnormal urine laboratory values, Urine Protein [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal urine laboratory values, Urine Protein
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal urine laboratory values, Urine Protein [units: participants]
Baseline	2	1
Week 6	1	1
Week 12	2	1
Week 18	1	0
Week 24	2	1
Week 36	2	0
Week 48	1	1
Week 60	3	1
Week 72	3	1
Week 84	2	1
Week 96	1	0

No statistical analysis provided for Safety and tolerability in terms of abnormal urine laboratory values, Urine Protein

38. Primary Outcome Measure: Safety and tolerability in terms of abnormal ECG, abnormalities [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal ECG, abnormalities
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal ECG, abnormalities [units: participants]
Baseline	0	0
Week 24	0	0
Final Visit	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal ECG, abnormalities

39. Primary Outcome Measure: Safety and tolerability in terms of abnormal physical exams, Cardiovascular [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal physical exams, Cardiovascular
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal physical exams, Cardiovascular [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	1
Week 48	0	1
Week 60	0	1
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal physical exams, Cardiovascular

40. Primary Outcome Measure: Safety and tolerability in terms of abnormal physical exams, General Appearance [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal physical exams, General Appearance
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal physical exams, General Appearance [units: participants]
Baseline	1	2
Week 6	1	2
Week 12	1	2
Week 18	1	2
Week 24	1	2
Week 36	1	2
Week 48	1	2
Week 60	1	2
Week 72	1	2
Week 84	1	2
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal physical exams, General Appearance

41. Primary Outcome Measure: Safety and tolerability in terms of abnormal physical exams, Head and Neck [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal physical exams, Head and Neck
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal physical exams, Head and Neck [units: participants]
Baseline	0	1
Week 6	0	1
Week 12	0	1
Week 18	0	1
Week 24	0	1
Week 36	0	1
Week 48	0	1
Week 60	0	1
Week 72	0	1
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal physical exams, Head and Neck

42. Primary Outcome Measure: Safety and tolerability in terms of abnormal physical exams, Musculoskeletal/Extremities [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal physical exams, Musculoskeletal/Extremities
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal physical exams, Musculoskeletal/Extremities [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	1
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal physical exams, Musculoskeletal/Extremities

43. Primary Outcome Measure: Safety and tolerability in terms of abnormal physical exams, Skin [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal physical exams, Skin
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal physical exams, Skin [units: participants]
Baseline	3	2
Week 6	3	2
Week 12	3	2
Week 18	3	2
Week 24	3	2
Week 36	3	2
Week 48	3	2
Week 60	2	2
Week 72	2	2
Week 84	2	1
Week 96	2	1

No statistical analysis provided for Safety and tolerability in terms of abnormal physical exams, Skin

44. Primary Outcome Measure: Safety and tolerability in terms of abnormal vital signs [ Time Frame: 96 weeks ]

Measure Type	Primary
Measure Name	Safety and tolerability in terms of abnormal vital signs
Measure Description
Time Frame	96 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Sequence A	Rosuva/Placebo in the D3561C00004 cross-over phase
Sequence B	Placebo/Rosuva in the D3561C00004 cross-over phase

Measured Values

	Sequence A	Sequence B
Number of Participants Analyzed [units:participants]	4	5
Number of participants Analyzed	4	5
Safety and tolerability in terms of abnormal vital signs [units: participants]
Baseline	0	0
Week 6	0	0
Week 12	0	0
Week 18	0	0
Week 24	0	0
Week 36	0	0
Week 48	0	0
Week 60	0	0
Week 72	0	0
Week 84	0	0
Week 96	0	0

No statistical analysis provided for Safety and tolerability in terms of abnormal vital signs

45. Secondary Outcome Measure: Percent change in LDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in LDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in LDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline LDL-C] Geometric Mean (95% Confidence Interval)
Visit 1	-21.0 (-32.1 to -8.0)
Visit 2	-18.6 (-28.4 to -7.4)
Visit 3	-14.7 (-25.2 to -2.8)
Visit 4	-12.1 (-23.8 to 1.4)
Visit 5	-21.3 (-33.7 to -6.6)
Visit 6	-20.5 (-33.6 to -4.8)
Visit 7	-12.4 (-28.2 to 7.0)

No statistical analysis provided for Percent change in LDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

46. Secondary Outcome Measure: Percent change in HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline HDL-C] Geometric Mean (95% Confidence Interval)
Visit 1	12.3 (1.3 to 24.5)
Visit 2	19.0 (6.2 to 33.4)
Visit 3	5.2 (-8.4 to 20.8)
Visit 4	4.4 (-10.8 to 22.2)
Visit 5	4.4 (-12.7 to 24.9)
Visit 6	9.4 (-9.4 to 32.1)
Visit 7	3.8 (-13.1 to 23.9)

No statistical analysis provided for Percent change in HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

47. Secondary Outcome Measure: Percent change in Total Cholesterol (TC) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in Total Cholesterol (TC) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in Total Cholesterol (TC) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline TC] Geometric Mean (95% Confidence Interval)
Visit 1	-19.4 (-29.7 to -7.6)
Visit 2	-16.8 (-25.7 to -6.8)
Visit 3	-14.0 (-23.6 to -3.3)
Visit 4	-11.8 (-22.3 to 0.1)
Visit 5	-19.9 (-31.1 to -6.9)
Visit 6	-18.3 (-30.2 to -4.3)
Visit 7	-11.9 (-26.3 to 5.2)

No statistical analysis provided for Percent change in Total Cholesterol (TC) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

48. Secondary Outcome Measure: Percent change in Triglycerides (TG) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in Triglycerides (TG) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in Triglycerides (TG) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline TG] Geometric Mean (95% Confidence Interval)
Visit 1	-17.3 (-31.9 to 0.5)
Visit 2	-17.4 (-34.2 to 3.8)
Visit 3	-16.2 (-36.1 to 10.1)
Visit 4	-22.0 (-42.8 to 6.5)
Visit 5	-23.3 (-45.0 to 7.1)
Visit 6	-21.7 (-43.4 to 8.4)
Visit 7	-28.5 (-47.0 to -3.6)

No statistical analysis provided for Percent change in Triglycerides (TG) from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

49. Secondary Outcome Measure: Percent change in Non-HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in Non-HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in Non-HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline Non-HDL-C] Geometric Mean (95% Confidence Interval)
Visit 1	-21.7 (-32.7 to -9.0)
Visit 2	-19.2 (-28.8 to -8.3)
Visit 3	-15.7 (-25.7 to -4.3)
Visit 4	-13.3 (-24.3 to -0.7)
Visit 5	-22.1 (-33.8 to -8.4)
Visit 6	-21.0 (-33.2 to -6.5)
Visit 7	-13.2 (-28.1 to 4.8)

No statistical analysis provided for Percent change in Non-HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

50. Secondary Outcome Measure: Percent change in LDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in LDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in LDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline LDL-C/HDL-C] Geometric Mean (95% Confidence Interval)
Visit 1	-39.4 (-51.6 to -24.1)
Visit 2	-41.2 (-52.8 to -26.9)
Visit 3	-36.1 (-48.8 to -20.2)
Visit 4	-35.0 (-49.5 to -16.4)
Visit 5	-48.6 (-61.3 to -31.7)
Visit 6	-42.2 (-57.2 to -21.9)
Visit 7	-27.8 (-47.4 to -0.9)

No statistical analysis provided for Percent change in LDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

51. Secondary Outcome Measure: Percent change in TC/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in TC/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in TC/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline TC/HDL-C] Geometric Mean (95% Confidence Interval)
Visit 1	-30.6 (-38.3 to -21.9)
Visit 2	-29.4 (-38.5 to -18.9)
Visit 3	-20.5 (-32.0 to -7.0)
Visit 4	-16.6 (-30.7 to 0.4)
Visit 5	-24.1 (-38.6 to -6.2)
Visit 6	-29.2 (-43.2 to -11.7)
Visit 7	-15.6 (-33.7 to 7.5)

No statistical analysis provided for Percent change in TC/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

52. Secondary Outcome Measure: Percent change in Non-HDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in Non-HDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in Non-HDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline Non-HDL-C/HDL-C] Geometric Mean (95% Confidence Interval)
Visit 1	-32.9 (-41.2 to -23.3)
Visit 2	-31.5 (-41.2 to -20.3)
Visit 3	-22.3 (-34.3 to -8.1)
Visit 4	-18.1 (-32.8 to -0.3)
Visit 5	-26.3 (-41.3 to -7.4)
Visit 6	-31.8 (-46.0 to -13.9)
Visit 7	-17.6 (-36.2 to 6.5)

No statistical analysis provided for Percent change in Non-HDL-C/HDL-C from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

53. Secondary Outcome Measure: Percent change in ApoB from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in ApoB from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in ApoB from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline ApoB] Geometric Mean (95% Confidence Interval)
Visit 1	-20.5 (-29.8 to -9.9)
Visit 2	-18.7 (-26.7 to -9.8)
Visit 3	-15.2 (-23.9 to -5.6)
Visit 4	-10.5 (-20.4 to 0.5)
Visit 5	-17.2 (-27.9 to -4.9)
Visit 6	-19.2 (-30.2 to -6.5)
Visit 7	-9.5 (-23.5 to 7.2)

No statistical analysis provided for Percent change in ApoB from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

54. Secondary Outcome Measure: Percent change in ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline ApoA-1] Geometric Mean (95% Confidence Interval)
Visit 1	8.0 (0.0 to 16.6)
Visit 2	7.0 (-2.3 to 17.1)
Visit 3	5.3 (-4.9 to 16.7)
Visit 4	6.5 (-5.3 to 19.7)
Visit 5	1.0 (-11.5 to 15.3)
Visit 6	10.7 (-2.6 to 25.7)
Visit 7	1.6 (-12.9 to 18.4)

No statistical analysis provided for Percent change in ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

55. Secondary Outcome Measure: Percent change in ApoB/ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Percent change in ApoB/ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	9
Number of participants Analyzed	9
Percent change in ApoB/ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis [units: % change from baseline ApoB/ApoA-1] Geometric Mean (95% Confidence Interval)
Visit 1	-23.3 (-34.3 to -10.5)
Visit 2	-22.1 (-32.7 to -9.8)
Visit 3	-18.9 (-31.2 to -4.4)
Visit 4	-15.7 (-30.2 to 1.7)
Visit 5	-17.0 (-33.1 to 2.8)
Visit 6	-26.0 (-41.1 to -7.0)
Visit 7	-14.7 (-33.7 to 9.7)

No statistical analysis provided for Percent change in ApoB/ApoA-1 from end of placebo of D3561C00004 to the end of D356NC00001, repeated measures analysis

56. Secondary Outcome Measure: Pharmacokinetic profile in terms of trough concentrations in pediatric HoFH taking a daily dose of rosuvastatin 40mg [ Time Frame: Up to 22 months ]

Measure Type	Secondary
Measure Name	Pharmacokinetic profile in terms of trough concentrations in pediatric HoFH taking a daily dose of rosuvastatin 40mg
Measure Description
Time Frame	Up to 22 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Full analysis set	Full analysis set, comprised of patient who received at least one dose of study drug.

Measured Values

	Full analysis set
Number of Participants Analyzed [units:participants]	1
Pharmacokinetic profile in terms of trough concentrations in pediatric HoFH taking a daily dose of rosuvastatin 40mg [units: ng/mL]
Day 292	9.00
Day 376	7.14

No statistical analysis provided for Pharmacokinetic profile in terms of trough concentrations in pediatric HoFH taking a daily dose of rosuvastatin 40mg

Serious Adverse Events

Time Frame	72 weeks
Additional Description	No text entered.

Reporting Groups

	Description
Overall	All patients

Serious Adverse Events

	Overall
Total, serious adverse events
# participants affected / at risk	0/9 (0.00%)

Other Adverse Events

Time Frame	72 weeks
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
Overall	All patients