Glycemic Efficacy and Renal Safety Study of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00663260
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 631
• Locations: 96
• Arms: 3
• Duration (Months): 36
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether dapagliflozin is effective in the treatment of type 2 diabetes in subjects with poor blood sugar control and moderate renal impairment

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Dapagliflozin; Drug: Dapagliflozin; Drug: Placebo	Phase 2/Phase 3

Detailed Description

All eligible subjects will receive a single-blind placebo medication during a 1-week lead-in period prior to randomization. All arms may include the addition of open label medication described (as needed for rescue based on protocol specific criteria). Rescue medication is defined as the addition of an approved, appropriate antihyperglycemic agent, except metformin, used according to conventional standards of care, to treat hyperglycemia, which may therefore allow the subject to remain in the trial

Study Design

• Study Type: Interventional
• Actual Enrollment: 631 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group, Randomized, Phase 2/3 Trial to Evaluate the Glycemic Efficacy, Renal Safety, Pharmacokinetics, and Pharmacodynamics of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment Who Have Inadequate Glycemic Control
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dapagliflozin (10 mg)	Drug: Dapagliflozin; Tablets, Oral, 10 mg, Once Daily, 104 weeks; Other Names: BMS-512148
Active Comparator: Dapagliflozin (5 mg)	Drug: Dapagliflozin; Tablets, Oral, 5 mg, Once Daily, 104 weeks; Other Names: BMS-512148
Placebo Comparator: Placebo	Drug: Placebo; Tablets, Oral, 0 mg, Once Daily, 104 weeks

Outcome Measures

Primary Outcome Measures

1. Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF] [From Baseline to Week 24]

   HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period.

Secondary Outcome Measures

1. Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF]) [From Baseline to Week 24]

   Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period

2. Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF]) [From Baseline to Week 24]

   Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females, ≥18 years old, with type 2 diabetes and with inadequate glycemic control

• Clinical diagnosis of moderate renal impairment

Exclusion Criteria:

• AST and /or ALT > 3.0 times the upper limit of normal

• Serum total bilirubin > 1.5 times ULN

• Symptoms of severely uncontrolled diabetes

• Currently unstable or serious cardiovascular, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vista Medical Research, Inc.	Mesa	Arizona	United States	85206
2	Valley Research	Fresno	California	United States	93720
3	Marin Endocrine Care & Research, Inc.	Greenbrae	California	United States	94904
4	Office Of Richard Cherlin, Md	Los Gatos	California	United States	95032
5	Diabetes Medical Center Of California	Northridge	California	United States	91325
6	Apex Research Of Riverside	Riverside	California	United States	92505
7	La Biomed At Harbor Ucla Med Ctr.	Torrance	California	United States	90502
8	Endocrine Associates Of The Rockies	Denver	Colorado	United States	80220
9	Panhandle Family Care Associates	Marianna	Florida	United States	32446
10	Genesis Clinical Research	Tampa	Florida	United States	33614
11	Endocrine Research Solutions, Inc.	Roswell	Georgia	United States	30076
12	Twin Cities Clinical Research	Brooklyn Center	Minnesota	United States	55430
13	Kcva Medical Center Research Svc (151)	Kansas City	Missouri	United States	64128
14	Va Nebraska-Western Iowa Health Care System (Nwihcs)	Omaha	Nebraska	United States	68105
15	University Of Medicine And Dentistry Of New Jersey	Voorhees	New Jersey	United States	08043
16	Winthrop University Hospital	Mineola	New York	United States	11501
17	Slocum-Dickson Medical Group, Pllc	New Hartford	New York	United States	13413
18	Community Health Care Of Manchester	Akron	Ohio	United States	44319
19	Center For Thyroid Diseases And Endocrinology	Beachwood	Ohio	United States	44122
20	Physician Research, Inc.	Zanesville	Ohio	United States	43701
21	Univ Of Oklahoma Health Science Center	Oklahoma City	Oklahoma	United States	73104
22	Rogue Valley Clinical Research	Medford	Oregon	United States	97504
23	Drexel University College Of Medicine	Philadelphia	Pennsylvania	United States	19102
24	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
25	Low Country Internal Medicine Of Sc, Pa	Charleston	South Carolina	United States	29406
26	Carolina Health Specialists	Myrtle Beach	South Carolina	United States	29572
27	Palmetto Clinical Research	Summerville	South Carolina	United States	29485
28	Research Institute Of Dallas	Dallas	Texas	United States	75231
29	Westbury Medical Clinic P.A.	Houston	Texas	United States	77005
30	The Strelitz Diabetes Center	Norfolk	Virginia	United States	23510
31	Capital Clinical Research Center	Olympia	Washington	United States	98502
32	Cedar Research Llc	Tacoma	Washington	United States	98405
33	Aurora Advanced Healthcare	Milwaukee	Wisconsin	United States	53209
34	Zablocki Veterans Affairs Medical Center	Milwaukee	Wisconsin	United States	53295
35	Local Institution	Capital Federal	Buenos Aires	Argentina	C1405BCJ
36	Local Institution	Mar Del Plata	Buenos Aires	Argentina	7600
37	Local Institution	Zarate	Buenos Aires	Argentina	2800
38	Local Institution	Buenos Aires		Argentina	C1012AAR
39	Local Institution	Buenos Aires		Argentina	C1408INH
40	Local Institution	Cordoba		Argentina	5000
41	Local Institution	Cordoba		Argentina	X5006CBI
42	Local Institution	Salta		Argentina	A4406CLA
43	Local Institution	Camperdown	New South Wales	Australia	2050
44	Local Institution	St Leonards	New South Wales	Australia	2065
45	Local Institution	Woollongong	New South Wales	Australia	2500
46	Local Institution	Launceston	Tasmania	Australia	7250
47	Local Institution	Calgary	Alberta	Canada	T3B 0M3
48	Local Institution	Winnipeg	Manitoba	Canada	R3E 3P4
49	Local Institution	Barrie	Ontario	Canada	L4M 7G1
50	Local Institution	Thornhill	Ontario	Canada	L4J 8L7
51	Local Institution	Toronto	Ontario	Canada	M4N 3M5
52	Local Institution	Toronto	Ontario	Canada	M4R 2G4
53	Local Institution	Gatineau	Quebec	Canada	J8V 2P5
54	Local Institution	Laval	Quebec	Canada	H7T 2P5
55	Local Institution	Sherbrooke	Quebec	Canada	J1G 5K2
56	Local Institution	Regina	Saskatchewan	Canada	S4P 0W5
57	Local Institution	Copenhagen Nv		Denmark	2400
58	Local Institution	Gentofte		Denmark	2820
59	Local Institution	Hvidovre		Denmark	2650
60	Local Institution	Besancon Cedex		France	25030
61	Local Institution	Brest Cedex		France	29609
62	Local Institution	Paris Cedex 10		France	75475
63	Local Institution	Paris		France	75877
64	Local Institution	Poitiers Cedex		France	86021
65	Local Institution	Indore	Madhya Pradesh	India	452001
66	Local Institution	Pune	Maharashtra	India	411 004
67	Local Institution	Bangalore		India	560 052
68	Local Institution	Bangalore		India	560034
69	Local Institution	Chennai		India	600029
70	Local Institution	Pune, Maharashtra		India	411011
71	Local Institution	Rajasthan		India	302 001
72	Local Institution	Chieri		Italy	10023
73	Local Institution	Chieti Scalo		Italy	66013
74	Local Institution	Modena		Italy	41100
75	Local Institution	Padova		Italy	35128
76	Local Institution	Perugia		Italy	06126
77	Local Institution	Pisa		Italy	56126
78	Local Institution	Roma		Italy	00189
79	Local Institution	Siena		Italy	53100
80	Local Institution	Df	Distrito Federal	Mexico	01120
81	Local Institution	Df	Distrito Federal	Mexico	06700
82	Local Institution	Df	Distrito Federal	Mexico	11800
83	Local Institution	Celaya	Guanajuato	Mexico	38000
84	Local Institution	Guadalajara	Jalisco	Mexico	44670
85	Local Institution	Monterrey	Nuevo Leon	Mexico	64460
86	Local Institution	Durango		Mexico	34075
87	Local Institution	Cercado De Lima	Lima	Peru	1
88	Local Institution	Arequipa		Peru
89	Local Institution	Lima		Peru	18
90	Local Institution	Lima		Peru	LIMA 13
91	Local Institution	Caguas		Puerto Rico	00725
92	Local Institution	San Juan		Puerto Rico	00909
93	Local Institution	Singapore		Singapore	119074
94	Local Institution	Barcelona		Spain	08036
95	Local Institution	San Sebastian De Los		Spain	28702
96	Local Institution	Vizcaya		Spain	48903

Sponsors and Collaborators

• AstraZeneca
• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Publication
• Publication long-term
• MB102029_Redacted_CSR_synopsis

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00663260
• Other Study ID Numbers: MB102-029
• First Posted: Apr 22, 2008
• Last Update Posted: Feb 10, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Dapagliflozin

Study Results

Participant Flow

Recruitment Details	Of 631 participants enrolled, 276 completed a qualification period. Of these 276 participants, 252 were randomized and received treatment. Of these 252 participants, 204 completed double-blind treatment period.

Arm/Group Title	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Arm/Group Description	Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Period Title: Overall Study
STARTED	84	83	85
COMPLETED	63	72	69
NOT COMPLETED	21	11	16

Baseline Characteristics

Arm/Group Title	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg	Total
Arm/Group Description	Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Total of all reporting groups
Overall Participants	84	83	85	252
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67 (8.6)	66 (8.9)	68 (7.7)	67 (8.4)
Age, Customized (Number) [Number]
Younger than 65 years	36 42.9%	39 47%	29 34.1%	104 41.3%
65 years and older	48 57.1%	44 53%	56 65.9%	148 58.7%
Sex/Gender, Customized (Number) [Number]
Male	53 63.1%	55 66.3%	56 65.9%	164 65.1%
Female	31 36.9%	28 33.7%	29 34.1%	88 34.9%
Race/Ethnicity, Customized (Number) [Number]
WHITE	69 82.1%	65 78.3%	77 90.6%	211 83.7%
BLACK OR AFRICAN AMERICAN	1 1.2%	7 8.4%	4 4.7%	12 4.8%
ASIAN	6 7.1%	4 4.8%	3 3.5%	13 5.2%
OTHER	8 9.5%	7 8.4%	1 1.2%	16 6.3%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	89.61 (20.046)	95.23 (20.909)	93.25 (17.309)	92.69 (19.529)
Pre-Enrollment Anti-Hyperglycemic Therapy (Number) [Number]
INSULIN-BASED REGIMEN	55 65.5%	54 65.1%	55 64.7%	164 65.1%
SULFONYLUREA-BASED REGIMEN	21 25%	21 25.3%	21 24.7%	63 25%
THIAZOLIINEDIONE-BASED REGIMEN	1 1.2%	1 1.2%	2 2.4%	4 1.6%
OTHER REGIMEN	7 8.3%	7 8.4%	7 8.2%	21 8.3%

Outcome Measures

1. Primary Outcome

Title	Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]
Description	HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)

Arm/Group Title	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Arm/Group Description	Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Measure Participants	82	83	82
Mean (Standard Error) [% of hemoglobin]	-0.32 (0.1701)	-0.41 (0.1701)	-0.44 (0.1708)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapagliflozin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.561
	Comments	Primary endpoints were tested at alpha=0.027 applying Dunnett's adjustment
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1448
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapagliflozin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.435
	Comments	Primary endpoints were tested at alpha=0.027 applying Dunnett's adjustment
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1457
	Estimation Comments

2. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])
Description	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received study medication and had nonmissing FPG values at baseline and Week 24 (LOCF)

Arm/Group Title	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Arm/Group Description	Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Measure Participants	83	83	85
Mean (Standard Error) [mg/dL]	8.4 (9.621)	-5.2 (9.548)	-0.6 (9.524)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapagliflozin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-13.6
	Confidence Interval	(2-Sided) 95%; -29.7 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.142
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapagliflozin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.0
	Confidence Interval	(2-Sided) 95%; -25.0 to 7.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.136
	Estimation Comments

3. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])
Description	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24 (LOCF)

Arm/Group Title	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Arm/Group Description	Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)	Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)	Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
Measure Participants	84	83	85
Mean (Standard Error) [kg]	0.27 (0.4872)	-1.54 (0.4815)	-1.89 (0.4693)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapagliflozin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -2.68 to -0.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4435
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapagliflozin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.16
	Confidence Interval	(2-Sided) 95%; -3.03 to -1.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4395
	Estimation Comments

Adverse Events

Time Frame	Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Arm/Group Title	Placebo		Dapagliflozin 5 mg		Dapagliflozin 10 mg
Arm/Group Description	Participants received dapagliflozin matching placebo once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label anti-diabetic therapy as rescue)		Participants received dapagliflozin 5 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)		Participants received dapagliflozin 10 mg once daily for up to 24 weeks (Subjects were to continue their original pre-enrollment anti-diabetic therapy; may include the addition of open-label metformin as rescue)
All Cause Mortality
	Placebo		Dapagliflozin 5 mg		Dapagliflozin 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dapagliflozin 5 mg		Dapagliflozin 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/84 (10.7%)		7/83 (8.4%)		12/85 (14.1%)
Blood and lymphatic system disorders
ANAEMIA	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
Cardiac disorders
MYOCARDIAL INFARCTION	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
ACUTE MYOCARDIAL INFARCTION	2/84 (2.4%)	2	0/83 (0%)	0	0/85 (0%)	0
CARDIAC FAILURE	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
CARDIOMYOPATHY	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
Eye disorders
RETINAL DETACHMENT	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Gastrointestinal disorders
INGUINAL HERNIA	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
General disorders
CHEST PAIN	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
OEDEMA	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
Immune system disorders
HYPERSENSITIVITY	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
Infections and infestations
SEPTIC SHOCK	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
CELLULITIS	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
PNEUMONIA	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
Injury, poisoning and procedural complications
TRAUMATIC BRAIN INJURY	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
Investigations
HEART RATE INCREASED	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Metabolism and nutrition disorders
HYPOGLYCAEMIA	0/84 (0%)	0	0/83 (0%)	0	2/85 (2.4%)	2
HYPERGLYCAEMIA	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
HYPERKALAEMIA	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
SPONDYLOLISTHESIS	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
TENDON DISORDER	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Nervous system disorders
CEREBRAL INFARCTION	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
SYNCOPE	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Renal and urinary disorders
URINARY RETENTION	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Reproductive system and breast disorders
BALANOPOSTHITIS	0/84 (0%)	0	1/83 (1.2%)	1	0/85 (0%)	0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/84 (1.2%)	1	0/83 (0%)	0	0/85 (0%)	0
Vascular disorders
HYPOTENSION	0/84 (0%)	0	0/83 (0%)	0	1/85 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Dapagliflozin 5 mg		Dapagliflozin 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/84 (46.4%)		45/83 (54.2%)		42/85 (49.4%)
Gastrointestinal disorders
DIARRHOEA	3/84 (3.6%)	3	3/83 (3.6%)	4	8/85 (9.4%)	9
NAUSEA	1/84 (1.2%)	1	3/83 (3.6%)	5	7/85 (8.2%)	7
General disorders
OEDEMA PERIPHERAL	4/84 (4.8%)	4	8/83 (9.6%)	10	4/85 (4.7%)	6
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	3/84 (3.6%)	4	3/83 (3.6%)	4	6/85 (7.1%)	7
NASOPHARYNGITIS	5/84 (6%)	8	6/83 (7.2%)	6	4/85 (4.7%)	5
GASTROENTERITIS	5/84 (6%)	6	1/83 (1.2%)	1	1/85 (1.2%)	1
Metabolism and nutrition disorders
HYPERKALAEMIA	10/84 (11.9%)	16	7/83 (8.4%)	9	5/85 (5.9%)	6
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN	3/84 (3.6%)	5	3/83 (3.6%)	3	7/85 (8.2%)	8
ARTHRALGIA	5/84 (6%)	6	5/83 (6%)	5	2/85 (2.4%)	2
BACK PAIN	6/84 (7.1%)	7	7/83 (8.4%)	8	2/85 (2.4%)	2
Nervous system disorders
DIZZINESS	4/84 (4.8%)	4	10/83 (12%)	14	5/85 (5.9%)	5
Renal and urinary disorders
POLLAKIURIA	3/84 (3.6%)	3	5/83 (6%)	7	10/85 (11.8%)	12
MICTURITION URGENCY	0/84 (0%)	0	5/83 (6%)	5	2/85 (2.4%)	3
Respiratory, thoracic and mediastinal disorders
COUGH	2/84 (2.4%)	3	8/83 (9.6%)	9	8/85 (9.4%)	10
Vascular disorders
HYPERTENSION	5/84 (6%)	6	1/83 (1.2%)	1	5/85 (5.9%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.