A study to evaluate the effect of dapagliflozin on blood glucose level and renal safety in patients with Type 2 Diabetes - DERIVE

Study identifier:D1690C00024

ClinicalTrials.gov identifier:NCT02413398

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group, Randomized, Phase III study to Evaluate the Glycemic Efficacy and Renal Safety of dapagliflozin in patients with Type 2 Diabetes Mellitus and Moderate Renal Impairment (CKD 3A) who have Inadequate Glycemic Control.

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 3

Healthy volunteers

Study drug

Dapagliflozin 10 mg, Matching Placebo for Dapagliflozin

Sex

All

Actual Enrollment

321

Study type

Interventional

Age

18 Years - 74 Years

Date

Study Start Date: 15 Jun 2015

Primary Completion Date: 07 Nov 2017

Study Completion Date: 07 Nov 2017

Study design

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

Verification:

Verified 01 Sept 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Toronto, ON, Canada, M4G 3E8

Location

Research Site

Halifax, NS, Canada, B3H 1V7

Location

Research Site

Brampton, ON, Canada, L6S 0S9

Location

Research Site

Huntsville, AL, United States, 35801

Location

Research Site

Cambridge, ON, Canada, N1R 6V6

Location

Research Site

Manassas, VA, United States, 20110

Location

Research Site

Huntington Beach, CA, United States, 92648

Location

Research Site

Kansas City, MO, United States, 64111

Arms	Assigned Interventions
Experimental: Dapagliflozin 10 mg Tablets, Oral, Once daily, 24 weeks	Drug: Dapagliflozin 10 mg Tablets administered orally once daily for 24 weeks. Randomization will be stratified by pre-enrolment anti-hyperglycemic therapy Other Name: Farxiga™
Placebo Comparator: Placebo Matching placebo to Dapagliflozin 10 mg tablet. Oral, Once daily, 24 weeks	Drug: Matching Placebo for Dapagliflozin Matching Placebo for Dapagliflozin tablets administered orally once daily for 24 weeks

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

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
Dapagliflozin 10mg QD	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo QD	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks

Participant Flow: Overall Study

	Dapagliflozin 10mg QD	Placebo QD
STARTED	160	161
COMPLETED	156	154
NOT COMPLETED	4	7
Lost to Follow-up	2	4
Withdrawal by Subject	1	1
Other Eligibility criteria	1	2

Baseline Characteristics

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

Reporting Groups

	Description
Dapagliflozin 10mg QD	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks

Baseline Measures

	Dapagliflozin 10mg QD	Placebo	Total
Number of Participants [units: Participants]	160	161	321
Age Continuous [units: Years] Mean ± Standard Deviation	65.3 ± 6.22	66.2 ± 6.49	65.8 ± 6.36
Age, Customized [units: ]
< 65 Years	64	46	110
>= 65 Years	96	115	211
Sex: Female, Male [units: ]
Female	69	70	139
Male	91	91	182
Race/Ethnicity, Customized [units: ]
American Indian Or Alaska Native	2	0	2
Asian	5	8	13
Black Or African American	11	12	23
Other	1	1	2
White	141	140	281
Body Mass Index [units: kg/m^2] Mean ± Standard Deviation	32.6 ± 4.7	31.6 ± 5.0	32.1 ± 4.9
Estimated Glomular Filtration Rate (eGFR) [units: mL/min/1.73 m^2] Mean ± Standard Deviation	51.8 ± 4.1	51.6 ± 3.8	51.7 ± 3.9
Urine Albumin-to-Creatinine Ratio (UACR) [units: mg/g] Mean ± Standard Deviation	226.91 ± 566.67	246.52 ± 775.49	236.78 ± 678.81

Outcome Measures

1. Primary Outcome Measure: Adjusted mean change from baseline in hemoglobin A1c (HbA1c) at Week 24 [ Time Frame: Baseline, Week 24 ]

Measure Type	Primary
Measure Name	Adjusted mean change from baseline in hemoglobin A1c (HbA1c) at Week 24
Measure Description	To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The "number analyzed" (142 dapaglifozin, 134 placebo) represents the number with change from baseline available at Week 24.
Time Frame	Baseline, Week 24
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.
For glycaemic measurements (HbA1c and FPG), all measurements after the first dose of rescue medication were excluded. For other non-glycaemic measurements (body weight and SBP), all measurements after the first dose of rescue medication were included.

Reporting Groups

	Description
Dapagliflozin	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks

Measured Values

	Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	142	134
Adjusted mean change from baseline in hemoglobin A1c (HbA1c) at Week 24 [units: percent] Mean (Standard Error)	-0.37 (0.10)	-0.03 (0.10)

Statistical Analysis 1 for Adjusted mean change from baseline in hemoglobin A1c (HbA1c) at Week 24

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.001
Mean Difference (Final Values)^[5]	-0.34
Standard Error of the mean	± 0.10
95% Confidence Interval	( -0.53 to -0.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference in adjusted mean change from baseline (MMRM model)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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 percent change from baseline in total body weight at Week 24. [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted mean percent change from baseline in total body weight at Week 24.
Measure Description	To compare the mean percent change from baseline in total body weight between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The "number analyzed" represents the number with change from baseline available at Week 24.
Time Frame	Baseline, Week 24
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
Dapagliflozin	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks

Measured Values

	Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	149	146
Adjusted mean percent change from baseline in total body weight at Week 24. [units: percent change] Mean (Standard Error)	-3.42 (0.32)	-2.02 (0.32)

Statistical Analysis 1 for Adjusted mean percent change from baseline in total body weight at Week 24.

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.001
Mean Difference (Final Values)^[5]	-1.43
Standard Error of the mean	± 0.37
95% Confidence Interval	( -2.15 to -0.69 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference in adjusted mean percent change from baseline (MMRM)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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 change from baseline in fasting plasma glucose (FPG) at Week 24. [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted mean change from baseline in fasting plasma glucose (FPG) at Week 24.
Measure Description	To compare the mean change from baseline in FPG between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The "number analyzed" represents the number with change from baseline available at Week 24.
Time Frame	Baseline, Week 24
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
Dapagliflozin	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks

Measured Values

	Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	135	134
Adjusted mean change from baseline in fasting plasma glucose (FPG) at Week 24. [units: mg/dL] Mean (Standard Error)	-21.46 (5.20)	-4.87 (5.13)

Statistical Analysis 1 for Adjusted mean change from baseline in fasting plasma glucose (FPG) at Week 24.

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.001
Mean Difference (Final Values)^[5]	-16.59
Standard Error of the mean	± 5.15
95% Confidence Interval	( -26.73 to -6.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference in adjusted mean change from baseline versus placebo (MMRM)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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 seated systolic blood pressure (SBP) at Week 24. [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted mean change from baseline in seated systolic blood pressure (SBP) at Week 24.
Measure Description	To compare the mean change from baseline in seated systolic blood pressure (SBP) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The "number analyzed" represents the number with change from baseline available at Week 24.
Time Frame	Baseline, Week 24
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
Dapagliflozin	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks

Measured Values

	Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	146	145
Adjusted mean change from baseline in seated systolic blood pressure (SBP) at Week 24. [units: mmHg] Mean (Standard Error)	-4.8 (1.5)	-1.7 (1.5)

Statistical Analysis 1 for Adjusted mean change from baseline in seated systolic blood pressure (SBP) at Week 24.

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.050
Mean Difference (Final Values)^[5]	-3.1
Standard Error of the mean	± 1.6
95% Confidence Interval	( -6.3 to 0.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference in adjusted mean change from baseline vs. placebo (MMRM)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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	Non-serious AEs were included up to the last day of double-blind treatment + 4 days. SAEs were recorded from the time of Informed Consent through included up to the last day of double-blind treatment + 30 days (or to the end of the 3-week follow-up period, whichever came first).
Additional Description	No text entered.

Reporting Groups

	Description
Dapagliflozin 10mg QD	10 mg Tablets, Oral, Once daily, 24 weeks
Placebo	Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks