Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes - DEPICT 2

Study identifier:MB102-230

ClinicalTrials.gov identifier:NCT02460978

EudraCT identifier:2014-004599-49

CTIS identifier:N/A

Study Complete

Official Title

A Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Dapagliflozin as an Add-on to Insulin Therapy in Subjects with Type 1 Diabetes Mellitus - Study Two

Medical condition

Type 1 Diabetes Mellitus

Phase

Phase 3

Healthy volunteers

Study drug

Dapagliflozin

Sex

All

Actual Enrollment

815

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 08 Jul 2015

Primary Completion Date: 02 Sept 2017

Study Completion Date: 18 Apr 2018

Study design

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

Verification:

Verified 01 Jan 2019 by AstraZeneca

Collaborators

Bristol-Myers Squibb

Inclusion and exclusion criteria

Location

Research Site

Cordoba, Argentina, X5006IKK

Location

Research Site

CABA, Argentina, 1056

Location

Research Site

Cordoba, Argentina, 5000

Location

Research Site

Buenos Aires, Argentina, C1405BCH

Location

Research Site

Ramos Mejía, Argentina, B1704ETD

Location

Research Site

Corrientes, Argentina, 3400

Location

Research Site

Leuven, Belgium, 3000

Location

Research Site

Brussels (Uccle), Belgium, 1180

Arms	Assigned Interventions
Experimental: Dapagliflozin 5 mg Dapagliflozin 5 mg tablet orally, once daily for 52 weeks	Drug: Dapagliflozin Tablets
Experimental: Dapagliflozin 10 mg Dapagliflozin 10 mg tablet orally, once daily for 52 weeks	Drug: Dapagliflozin Tablets
Placebo Comparator: Placebo Placebo tablet orally, once daily for 52 weeks	Other: Placebo for dapagliflozin Tablets

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 results on this form are from the 24 week short-term double-blind treatment period. This study was conducted at 148 centers in 13 countries from 8 July 2015 to 2 Sep 2017.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
815 participants were randomized. Of the 195 participants not randomized: 97 No longer met study criteria, 44 withdrew consent, 13 were lost to follow-up, and 41 did not continue for other reasons. Two participants did not receive any study drug and were excluded from analyses. Thus, the total number of subjects is 813.

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Participant Flow: Overall Study

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
STARTED	271	270	272
COMPLETED	244	245	239
NOT COMPLETED	27	25	33
Adverse Event	17	11	11
Withdrawal by Subject	5	5	14
Lost to Follow-up	2	3	1
Protocol Violation	1	1	1
Discontinued due to DKA/hypoglycemia	2	5	4
Pregnancy	0	0	2

Baseline Characteristics

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

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Baseline Measures

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS	Total
Number of Participants [units: Participants]	271	270	272	813
Age Continuous [units: Years] Mean ± Standard Deviation	42.7 ± 13.35	42.4 ± 12.80	43.0 ± 13.73	42.7 ± 13.29
Sex: Female, Male [units: Participants]
Female	153	149	153	455
Male	118	121	119	358
Race/Ethnicity, Customized [units: Participants]
Total	271	270	272	813
White	210	219	208	637
Black or African-American	4	7	1	12
Asian	57	44	59	160
Other	0	0	4	4

Outcome Measures

1. Primary Outcome Measure: Adjusted mean change from baseline in HbA1c at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Primary
Measure Name	Adjusted mean change from baseline in HbA1c at Week 24
Measure Description	To compare the change from baseline in HbA1c between dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Time Frame	Baseline and 24 weeks
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 analysis population for this endpoint is the number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value. The full analysis set consists of all randomized subjects who took at least one dose of double-blind study medication during the short-term double-blind period.

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	266	267	267
Adjusted mean change from baseline in HbA1c at Week 24 [units: HbA1c (%)] Least Squares Mean (95% Confidence Interval)	-0.34 (-0.43 to -0.25)	-0.39 (-0.48 to -0.30)	0.03 (-0.06 to 0.12)

Statistical Analysis 1 for Adjusted mean change from baseline in HbA1c at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.37
Standard Error of the mean	± 0.0579
95% Confidence Interval	( -0.49 to -0.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Model is adjusted for baseline HbA1c, treatment, week, randomization stratum, weektreatment, and weekbaseline HbA1c.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean change from baseline in HbA1c at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.42
Standard Error of the mean	± 0.0578
95% Confidence Interval	( -0.53 to -0.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Model is adjusted for baseline HbA1c, treatment, week, randomization stratum, weektreatment, and weekbaseline HbA1c.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Adjusted mean percentage change from baseline in total daily insulin dose at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Adjusted mean percentage change from baseline in total daily insulin dose at Week 24
Measure Description	To compare the percent change from baseline in total daily insulin dose with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Time Frame	Baseline and 24 weeks
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.
Number of subjects in full analysis set with non-missing baseline and at least one post-baseline value

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	270	267	266
Adjusted mean percentage change from baseline in total daily insulin dose at Week 24 [units: Percentage change] Least Squares Mean (95% Confidence Interval)	-8.73 (-11.09 to -6.31)	-9.05 (-11.43 to -6.60)	2.29 (-0.41 to 5.06)

Statistical Analysis 1 for Adjusted mean percentage change from baseline in total daily insulin dose at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-10.78
Standard Error of the mean	± 1.5291
95% Confidence Interval	( -13.73 to -7.72 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean percentage change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for ln(baseline), treatment, week, randomization stratum, weektreatment, weekln(baseline).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean percentage change from baseline in total daily insulin dose at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-11.08
Standard Error of the mean	± 1.5331
95% Confidence Interval	( -14.04 to -8.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean percentage change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for ln(baseline), treatment, week, randomization stratum, weektreatment, and weekln(baseline).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Adjusted mean percentage change from baseline in body weight at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Adjusted mean percentage change from baseline in body weight at Week 24
Measure Description	To compare the percentage change from baseline in body weight with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Time Frame	Baseline and 24 weeks
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.
Number of subjects in full analysis set with non-missing baseline and at least one post-baseline value

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	269	269	272
Adjusted mean percentage change from baseline in body weight at Week 24 [units: Percentage change] Least Squares Mean (95% Confidence Interval)	-3.22 (-3.76 to -2.69)	-3.76 (-4.29 to -3.22)	-0.02 (-0.57 to 0.54)

Statistical Analysis 1 for Adjusted mean percentage change from baseline in body weight at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-3.21
Standard Error of the mean	± 0.3829
95% Confidence Interval	( -3.96 to -2.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean percentage change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for ln(baseline), treatment, week, randomization stratum, weektreatment, and weekln(baseline).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean percentage change from baseline in body weight at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-3.74
Standard Error of the mean	± 0.3812
95% Confidence Interval	( -4.49 to -2.99 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean percentage change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for ln(baseline), treatment, week, randomization stratum, weektreatment, and weekln(baseline).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Adjusted mean change from baseline in 24-hour continuous glucose monitoring (CGM) mean value at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Adjusted mean change from baseline in 24-hour continuous glucose monitoring (CGM) mean value at Week 24
Measure Description	To compare the change from baseline in mean value of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Time Frame	Baseline and 24 weeks
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 subjects in the full analysis set with non-missing baseline and at least one post-baseline value

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	252	255	257
Adjusted mean change from baseline in 24-hour continuous glucose monitoring (CGM) mean value at Week 24 [units: mg/dL] Least Squares Mean (95% Confidence Interval)	-6.46 (-10.04 to -2.87)	-10.54 (-14.14 to -6.94)	9.20 (5.57 to 12.83)

Statistical Analysis 1 for Adjusted mean change from baseline in 24-hour continuous glucose monitoring (CGM) mean value at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-15.66
Standard Error of the mean	± 2.3468
95% Confidence Interval	( -20.26 to -11.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline, treatment, week, randomization stratum, weektreatment, and weekbaseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean change from baseline in 24-hour continuous glucose monitoring (CGM) mean value at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-19.74
Standard Error of the mean	± 2.3419
95% Confidence Interval	( -24.34 to -15.14 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline, treatment, week, randomization stratum, weektreatment, and weekbaseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Adjusted mean change from baseline in 24-hour CGM mean amplitude of glycemic excursion (MAGE) value at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Adjusted mean change from baseline in 24-hour CGM mean amplitude of glycemic excursion (MAGE) value at Week 24
Measure Description	To compare the change from baseline in mean amplitude of glucose excursions (MAGE) of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Time Frame	Baseline and 24 weeks
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.
Number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	252	255	257
Adjusted mean change from baseline in 24-hour CGM mean amplitude of glycemic excursion (MAGE) value at Week 24 [units: mg/dL] Least Squares Mean (95% Confidence Interval)	-10.17 (-13.90 to -6.45)	-9.68 (-13.44 to -5.93)	-0.33 (-4.12 to 3.46)

Statistical Analysis 1 for Adjusted mean change from baseline in 24-hour CGM mean amplitude of glycemic excursion (MAGE) value at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-9.85
Standard Error of the mean	± 2.4519
95% Confidence Interval	( -14.66 to -5.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline, treatment, week, randomization stratum, weektreatment, and weekbaseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean change from baseline in 24-hour CGM mean amplitude of glycemic excursion (MAGE) value at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0001
Mean Difference (Final Values)^[5]	-9.36
Standard Error of the mean	± 2.4487
95% Confidence Interval	( -14.16 to -4.55 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline, treatment, week, randomization stratum, weektreatment, and weekbaseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24
Measure Description	To compare the change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of >70 mg/dL and <=180 mg/dL with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Time Frame	Baseline and 24 weeks
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.
Number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	252	255	257
Change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24 [units: % of readings] Least Squares Mean (95% Confidence Interval)	5.92 (4.32 to 7.52)	7.60 (5.98 to 9.21)	-3.10 (-4.73 to -1.47)

Statistical Analysis 1 for Change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	9.02
Standard Error of the mean	± 1.0415
95% Confidence Interval	( 6.97 to 11.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline, treatment, week, randomization stratum, weektreatment, and weekbaseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	10.70
Standard Error of the mean	± 1.0396
95% Confidence Interval	( 8.66 to 12.74 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference vs. placebo in adjusted mean change from baseline
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline, treatment, week, randomization stratum, weektreatment, and weekbaseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Percentage of subjects with HbA1c reduction from baseline to week 24 last observation carried forward (LOCF) >= 0.5% and without severe hypoglycemia events at Week 24 [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Percentage of subjects with HbA1c reduction from baseline to week 24 last observation carried forward (LOCF) >= 0.5% and without severe hypoglycemia events at Week 24
Measure Description	To compare dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin for the proportion of subjects achieving an HbA1c reduction from baseline to Week 24 visit >=0.5% without severe hypoglycemia events
Time Frame	Baseline and 24 weeks
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.
Number of subjects in the full analysis set with non-missing baseline and Week 24 (LOCF) values.

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Measured Values

	DAPA 5 MG + INS	DAPA 10 MG + INS	PLA + INS
Number of Participants Analyzed [units:participants]	266	267	269
Percentage of subjects with HbA1c reduction from baseline to week 24 last observation carried forward (LOCF) >= 0.5% and without severe hypoglycemia events at Week 24 [units: Participants]	105	111	54

Statistical Analysis 1 for Percentage of subjects with HbA1c reduction from baseline to week 24 last observation carried forward (LOCF) >= 0.5% and without severe hypoglycemia events at Week 24

Groups^[1]	DAPA 5 MG + INS, PLA + INS
Method^[3]	Regression, Logistic
P-Value^[4]	<0.0001
Odds Ratio (OR)^[5]	2.71
Standard Error of the mean	± 0.2058
95% Confidence Interval	( 1.81 to 4.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio vs. Placebo
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline HbA1c and randomization strata
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Percentage of subjects with HbA1c reduction from baseline to week 24 last observation carried forward (LOCF) >= 0.5% and without severe hypoglycemia events at Week 24

Groups^[1]	DAPA 10 MG + INS, PLA + INS
Method^[3]	Regression, Logistic
P-Value^[4]	<0.0001
Odds Ratio (OR)^[5]	3.07
Standard Error of the mean	± 0.2054
95% Confidence Interval	( 2.05 to 4.60 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio vs. Placebo
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for baseline HbA1c and randomization strata
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Additional Description	No text entered.

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Serious Adverse Events

DAPA 5 MG + INS

DAPA 10 MG + INS

PLA + INS

Total, serious adverse events

# participants affected / at risk

18/271 (6.64%)

7/270 (2.59%)

5/272 (1.84%)

Metabolism and nutrition disorders

Diabetic ketoacidosis¹,^†

# participants affected / at risk

7/271 (2.58%)

3/270 (1.11%)

0/272 (0.00%)

# events

Metabolism and nutrition disorders

Hypoglycemia¹,^†

# participants affected / at risk

3/271 (1.11%)

0/270 (0.00%)

1/272 (0.37%)

# events

Metabolism and nutrition disorders

Ketoacidosis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Metabolism and nutrition disorders

Ketosis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Metabolism and nutrition disorders

Lactic acidosis¹,^†

# participants affected / at risk

0/271 (0.00%)

0/270 (0.00%)

1/272 (0.37%)

# events

Nervous system disorders

Cerebral haemorrhage¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Nervous system disorders

Coma¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Nervous system disorders

Diabetic hyperglycaemic coma¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Nervous system disorders

Seizure¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

0/271 (0.00%)

0/270 (0.00%)

1/272 (0.37%)

# events

Nervous system disorders

Hypoglycaemic coma¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Nervous system disorders

Hypoglycaemic seizure¹,^†

# participants affected / at risk

2/271 (0.74%)

0/270 (0.00%)

0/272 (0.00%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Injury, poisoning and procedural complications

Subarachnoid haemorrhage¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Injury, poisoning and procedural complications

Foot fracture¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/271 (0.00%)

0/270 (0.00%)

1/272 (0.37%)

# events

Gastrointestinal disorders

Enteritis¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

General disorders

Chest pain¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/271 (0.00%)

1/270 (0.37%)

0/272 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Infections and infestations

Labyrinthitis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

Pregnancy, puerperium and perinatal conditions

Abortion spontaneous¹,^†

# participants affected / at risk

0/271 (0.00%)

0/270 (0.00%)

1/272 (0.37%)

# events

Renal and urinary disorders

Acute prerenal failure¹,^†

# participants affected / at risk

1/271 (0.37%)

0/270 (0.00%)

0/272 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 20.0

Other Adverse Events

Time Frame	All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
DAPA 5 MG + INS	Dapagliflozin 5 mg plus insulin
DAPA 10 MG + INS	Dapagliflozin 10 mg plus insulin
PLA + INS	Placebo plus insulin

Other Adverse Events

DAPA 5 MG + INS

DAPA 10 MG + INS

PLA + INS

Total, other (not including serious) adverse events

# participants affected / at risk

79/271 (29.15%)

77/270 (28.52%)

63/272 (23.16%)

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

39/271 (14.39%)

44/270 (16.30%)

42/272 (15.44%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

10/271 (3.69%)

15/270 (5.56%)

10/272 (3.68%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

22/271 (8.12%)

14/270 (5.19%)

6/272 (2.21%)

# events

General disorders

Thirst¹,^†

# participants affected / at risk

6/271 (2.21%)

14/270 (5.19%)

1/272 (0.37%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

16/271 (5.90%)

12/270 (4.44%)

12/272 (4.41%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 20.0

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 an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.

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
No text entered.

Results Point of Contact

Name/Title:	Anna Maria Langkilde
Organization:	AstraZeneca
Phone	+46 31 7761000
E-mail:	[email protected]

Documents available

MB102230_CSP
Download
MB102230_SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Anna Maria Langkilde

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

MB102230_CSP

MB102230_SAP

Trial Results Summaries