Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects with Metastatic Bone Disease

Study identifier:D8180C00034

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase II, Randomised, Open-Label, Pilot Study to Evaluate the Safety and Effects on Bone Resorption of AZD0530 in Patients with Prostate Cancer or Breast Cancer with Metastatic Bone Disease.

Medical condition

Breast Cancer

Phase

Phase 2

Healthy volunteers

Study drug

AZD0530, Zoledronic Acid

Sex

All

Actual Enrollment

139

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Feb 2008

Primary Completion Date: 01 Jan 2010

Study Completion Date: 01 Aug 2012

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2012 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

EDMONTON, AB, Canada

Location

Research Site

VANCOUVER, BC, Canada

Location

Research Site

TORONTO, ON, Canada

Location

Research Site

MONTREAL, QC, Canada

Location

Research Site

QUEBEC, QC, Canada

Location

Research Site

ARHUS N, Denmark

Location

Research Site

FREDERICA, Denmark

Location

Research Site

HERLEV, Denmark

Arms	Assigned Interventions
Experimental: AZD0530 175 mg AZD0530 (saracatinib) 175 mg once daily	Drug: AZD0530 Daily oral dose Other Name: Saracatinib
Experimental: Zoledronic Acid 4 mg Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period	-

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Randomised=full analysis set: AZD0530 175mg=69, Zoledronic acid 4mg=70; safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69

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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Participant Flow: Overall Study

	AZD0530 175 mg	Zoledronic Acid 4 mg
STARTED	69^[1]	70^[2]
30 days follow-up	41^[3]	67^[4]
COMPLETED	56^[5]	68^[6]
NOT COMPLETED	13	2
Adverse Event	10	0
Death	1	0
Dev. of study specific discon. criteria	1	0
AZ study team decision	0	1
Incorrectly enrolled	1	0
Withdrawal by Subject	0	1

[1]	Randomised
[2]	Randomised
[3]	30 days after last dose
[4]	30 days after last dose
[5]	4-week treatment period
[6]	4-week treatment period

Baseline Characteristics

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

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Baseline Measures

	AZD0530 175 mg	Zoledronic Acid 4 mg	Total
Number of Participants [units: Participants]	69	70	139
Age Continuous [units: Years] Mean ± Standard Deviation	67.6 ± 8.35	67.3 ± 11.58	67.4 ± 10.07
Gender, Male/Female [units: Participants]
Female	11	12	23
Male	58	58	116

Outcome Measures

1. Primary Outcome Measure: Percentage change from baseline in serum beta C-terminal cross-linking telopeptide of Type I collagen (betaCTX) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Primary
Measure Name	Percentage change from baseline in serum beta C-terminal cross-linking telopeptide of Type I collagen (betaCTX) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	46	65
Percentage change from baseline in serum beta C-terminal cross-linking telopeptide of Type I collagen (betaCTX) at Week 4 [units: Percentage change in betaCTX] Geometric Mean (95% Confidence Interval)	-71.1 (-75.9 to -65.4)	-68.4 (-73.0 to -63.2)

No statistical analysis provided for Percentage change from baseline in serum beta C-terminal cross-linking telopeptide of Type I collagen (betaCTX) at Week 4

2. Secondary Outcome Measure: Percentage change from baseline in serum bone-specific alkaline phosphatase (bALP) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in serum bone-specific alkaline phosphatase (bALP) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	48	66
Percentage change from baseline in serum bone-specific alkaline phosphatase (bALP) at Week 4 [units: Percentage change in bALP] Geometric Mean (95% Confidence Interval)	-13.2 (-24.4 to -0.3)	-3.1 (-13.9 to 9.1)

No statistical analysis provided for Percentage change from baseline in serum bone-specific alkaline phosphatase (bALP) at Week 4

3. Secondary Outcome Measure: Percentage change from baseline in serum cross-linked C-terminal telopeptide of Type I collagen (ICTP) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in serum cross-linked C-terminal telopeptide of Type I collagen (ICTP) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	47	66
Percentage change from baseline in serum cross-linked C-terminal telopeptide of Type I collagen (ICTP) at Week 4 [units: Percentage change in ICTP] Geometric Mean (95% Confidence Interval)	-40.2 (-46.3 to -33.4)	7.4 (-2.0 to 17.7)

No statistical analysis provided for Percentage change from baseline in serum cross-linked C-terminal telopeptide of Type I collagen (ICTP) at Week 4

4. Secondary Outcome Measure: Percentage change from baseline in serum N-terminal propeptide of Type I procollagen (PINP) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in serum N-terminal propeptide of Type I procollagen (PINP) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	48	66
Percentage change from baseline in serum N-terminal propeptide of Type I procollagen (PINP) at Week 4 [units: Percentage change in PINP] Geometric Mean (95% Confidence Interval)	-26.1 (-36.0 to -14.7)	-29.5 (-37.7 to -20.3)

No statistical analysis provided for Percentage change from baseline in serum N-terminal propeptide of Type I procollagen (PINP) at Week 4

5. Secondary Outcome Measure: Percentage change from baseline in serum tartrate-resistant acid phosphatase 5b (TRAP5b) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in serum tartrate-resistant acid phosphatase 5b (TRAP5b) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	48	65
Percentage change from baseline in serum tartrate-resistant acid phosphatase 5b (TRAP5b) at Week 4 [units: Percentage change in TRAP5b] Geometric Mean (95% Confidence Interval)	-36.9 (-42.7 to -30.4)	-43.4 (-48.0 to -38.4)

No statistical analysis provided for Percentage change from baseline in serum tartrate-resistant acid phosphatase 5b (TRAP5b) at Week 4

6. Secondary Outcome Measure: Percentage change from baseline in urine N-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (NTx/Cr) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in urine N-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (NTx/Cr) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	46	62
Percentage change from baseline in urine N-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (NTx/Cr) at Week 4 [units: Percentage change in NTx/Cr] Geometric Mean (95% Confidence Interval)	-57.2 (-65.7 to -46.6)	-70.1 (-75.4 to -63.8)

No statistical analysis provided for Percentage change from baseline in urine N-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (NTx/Cr) at Week 4

7. Secondary Outcome Measure: Percentage change from baseline in urine alpha-alpha C-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (aaCTx/Cr) at Week 4 [ Time Frame: Baseline to Week 4 ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in urine alpha-alpha C-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (aaCTx/Cr) at Week 4
Measure Description	Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame	Baseline to Week 4
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.
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	41	49
Percentage change from baseline in urine alpha-alpha C-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (aaCTx/Cr) at Week 4 [units: Percentage change in aaCTx/Cr] Geometric Mean (95% Confidence Interval)	-68.2 (-76.7 to -56.5)	-82.8 (-87.1 to -77.0)

No statistical analysis provided for Percentage change from baseline in urine alpha-alpha C-terminal cross-linking telopeptide of Type I collagen normalised to creatinine (aaCTx/Cr) at Week 4

8. Secondary Outcome Measure: Saracatinib: area under the curve at steady state (AUCss) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	Saracatinib: area under the curve at steady state (AUCss)
Measure Description	Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses.
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
Saracatinib: area under the curve at steady state (AUCss) [units: ng•hr/ml] Median (Full Range)	7261 (3960 to 21500)

No statistical analysis provided for Saracatinib: area under the curve at steady state (AUCss)

9. Secondary Outcome Measure: Saracatinib: plasma clearance at steady state (CLss/F) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	Saracatinib: plasma clearance at steady state (CLss/F)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
Saracatinib: plasma clearance at steady state (CLss/F) [units: L/h] Median (Full Range)	24.10 (8.15 to 44.2)

No statistical analysis provided for Saracatinib: plasma clearance at steady state (CLss/F)

10. Secondary Outcome Measure: Saracatinib: maximum plasma concentration at steady state (Css,max) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	Saracatinib: maximum plasma concentration at steady state (Css,max)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
Saracatinib: maximum plasma concentration at steady state (Css,max) [units: ng/ml] Median (Full Range)	396.0 (190 to 1170)

No statistical analysis provided for Saracatinib: maximum plasma concentration at steady state (Css,max)

11. Secondary Outcome Measure: Saracatinib: minimum plasma concentration at steady state (Css,min) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	Saracatinib: minimum plasma concentration at steady state (Css,min)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
Saracatinib: minimum plasma concentration at steady state (Css,min) [units: ng/ml] Median (Full Range)	229.0 (99.1 to 770)

No statistical analysis provided for Saracatinib: minimum plasma concentration at steady state (Css,min)

12. Secondary Outcome Measure: Saracatinib: time to Cssmax (Tmax) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	Saracatinib: time to Cssmax (Tmax)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
Saracatinib: time to Cssmax (Tmax) [units: h] Median (Full Range)	4.0 (2 to 9)

No statistical analysis provided for Saracatinib: time to Cssmax (Tmax)

13. Secondary Outcome Measure: N-desmethyl metabolite of saracatinib: area under the curve at steady state (AUCss) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	N-desmethyl metabolite of saracatinib: area under the curve at steady state (AUCss)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
N-desmethyl metabolite of saracatinib: area under the curve at steady state (AUCss) [units: ng.h/ml] Median (Full Range)	1069 (529 to 5100)

No statistical analysis provided for N-desmethyl metabolite of saracatinib: area under the curve at steady state (AUCss)

14. Secondary Outcome Measure: N-desmethyl metabolite of saracatinib: maximum plasma concentration at steady state (Css,max) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	N-desmethyl metabolite of saracatinib: maximum plasma concentration at steady state (Css,max)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
N-desmethyl metabolite of saracatinib: maximum plasma concentration at steady state (Css,max) [units: ng/ml] Median (Full Range)	62.80 (25.3 to 253)

No statistical analysis provided for N-desmethyl metabolite of saracatinib: maximum plasma concentration at steady state (Css,max)

15. Secondary Outcome Measure: N-desmethyl metabolite of saracatinib: minimum plasma concentration at steady state (Css,min) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	N-desmethyl metabolite of saracatinib: minimum plasma concentration at steady state (Css,min)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
N-desmethyl metabolite of saracatinib: minimum plasma concentration at steady state (Css,min) [units: ng/ml] Median (Full Range)	34.30 (16.6 to 230)

No statistical analysis provided for N-desmethyl metabolite of saracatinib: minimum plasma concentration at steady state (Css,min)

16. Secondary Outcome Measure: N-desmethyl metabolite of saracatinib: AUCss metabolite to parent ratio [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	N-desmethyl metabolite of saracatinib: AUCss metabolite to parent ratio
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
N-desmethyl metabolite of saracatinib: AUCss metabolite to parent ratio [units: Ratio] Median (Full Range)	0.1420 (0.081 to 0.354)

No statistical analysis provided for N-desmethyl metabolite of saracatinib: AUCss metabolite to parent ratio

17. Secondary Outcome Measure: N-desmethyl metabolite of saracatinib: time to Cssmax (Tmax) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ]

Measure Type	Secondary
Measure Name	N-desmethyl metabolite of saracatinib: time to Cssmax (Tmax)
Measure Description
Time Frame	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
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
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Measured Values

	AZD0530 175 mg	Zoledronic Acid 4 mg
Number of Participants Analyzed [units:participants]	51	0
N-desmethyl metabolite of saracatinib: time to Cssmax (Tmax) [units: h] Median (Full Range)	2.0 (2 to 9)

No statistical analysis provided for N-desmethyl metabolite of saracatinib: time to Cssmax (Tmax)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Serious Adverse Events

AZD0530 175 mg

Zoledronic Acid 4 mg

Total, serious adverse events

# participants affected / at risk

11/68 (16.18%)

4/69 (5.80%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Cardiac disorders

Cardiac Arrest¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Cardiac disorders

Myocardial Infarction¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

General disorders

General Physical Health Deterioration¹,^†

# participants affected / at risk

0/68 (0.00%)

1/69 (1.45%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/68 (2.94%)

0/69 (0.00%)

Infections and infestations

Viral Infection¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Injury, poisoning and procedural complications

Blood Creatinine Increased¹,^†

# participants affected / at risk

0/68 (0.00%)

1/69 (1.45%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/68 (0.00%)

1/69 (1.45%)

Musculoskeletal and connective tissue disorders

Bone Pain¹,^†

# participants affected / at risk

0/68 (0.00%)

1/69 (1.45%)

Musculoskeletal and connective tissue disorders

Muscle Spasms¹,^†

# participants affected / at risk

0/68 (0.00%)

1/69 (1.45%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Pain¹,^†

# participants affected / at risk

0/68 (0.00%)

1/69 (1.45%)

Nervous system disorders

Cerebral Haemorrhage¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Renal and urinary disorders

Renal Failure¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Renal and urinary disorders

Renal Failure Acute¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pulmonary Oedema¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

Vascular disorders

Deep Vein Thrombosis¹,^†

# participants affected / at risk

1/68 (1.47%)

0/69 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD0530 175 mg	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Other Adverse Events

AZD0530 175 mg

Zoledronic Acid 4 mg

Total, other (not including serious) adverse events

# participants affected / at risk

51/68 (75.00%)

46/69 (66.67%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

16/68 (23.53%)

3/69 (4.35%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

13/68 (19.12%)

4/69 (5.80%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

10/68 (14.71%)

5/69 (7.25%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

7/68 (10.29%)

5/69 (7.25%)

General disorders

Influenza Like Illness¹,^†

# participants affected / at risk

3/68 (4.41%)

8/69 (11.59%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

4/68 (5.88%)

6/69 (8.70%)

General disorders

Fatigue¹,^†

# participants affected / at risk

5/68 (7.35%)

4/69 (5.80%)

General disorders

Asthenia¹,^†

# participants affected / at risk

4/68 (5.88%)

1/69 (1.45%)

General disorders

Oedema Peripheral¹,^†

# participants affected / at risk

4/68 (5.88%)

2/69 (2.90%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/68 (0.00%)

11/69 (15.94%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

6/68 (8.82%)

2/69 (2.90%)

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

8/68 (11.76%)

1/69 (1.45%)

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

1/68 (1.47%)

7/69 (10.14%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

8/68 (11.76%)

4/69 (5.80%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Pain¹,^†

# participants affected / at risk

5/68 (7.35%)

8/69 (11.59%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

4/68 (5.88%)

7/69 (10.14%)

Musculoskeletal and connective tissue disorders

Bone Pain¹,^†

# participants affected / at risk

3/68 (4.41%)

5/69 (7.25%)

Musculoskeletal and connective tissue disorders

Neck Pain¹,^†

# participants affected / at risk

1/68 (1.47%)

4/69 (5.80%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

5/68 (7.35%)

5/69 (7.25%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

5/68 (7.35%)

2/69 (2.90%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Non-compliant patients were excluded from the biomarker analysis, in order to accurately assess effects due to treatment. The compliance criteria did not apply to the zoledronic acid arm, which led to an imbalance in the number of subjects analysed.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Cancer Study Locator (US and Canada only)
Download
https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=415&filename=CSR-D8180C00034.pdf
Download
CSR-D8180C00034.pdf
Download
CSR-D8180C00034.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AZD0530 Clinical Trials Mailbox

AZD0530ClinicalTrialsMailbox@astrazeneca.com

Contact Backup

AstraZeneca Cancer Study Locator Service

877-400-4656

astrazeneca@emergingmed.com

Investigators

Principal Investigator

Richard Finkelman

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Cancer Study Locator (US and Canada only)

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=415&filename=CSR-D8180C00034.pdf

CSR-D8180C00034.pdf

CSR-D8180C00034.pdf

Trial Results Summaries