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

Study identifier:MB102-029

ClinicalTrials.gov identifier:NCT00663260

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Diabetes Mellitus, Type 2

Phase

Phase 2/3

Healthy volunteers

Study drug

Dapagliflozin, Placebo

Sex

All

Actual Enrollment

631

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Jun 2008

Primary Completion Date: 01 Dec 2009

Study Completion Date: 01 Jun 2011

Study design

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

Verification:

Verified 01 Dec 2016 by AstraZeneca Pharmaceuticals

Collaborators

Bristol-Myers Squibb

Inclusion and exclusion criteria

Location

Marin Endocrine Care & Research, Inc.

Greenbrae, CA, United States, 94904

Location

Office Of Richard Cherlin, Md

Los Gatos, CA, United States, 95032

Location

Low Country Internal Medicine Of Sc, Pa

Charleston, SC, United States, 29406

Location

Carolina Health Specialists

Myrtle Beach, SC, United States, 29572

Location

Cedar Research Llc

Tacoma, WA, United States, 98405

Location

Aurora Advanced Healthcare

Milwaukee, WI, United States, 53209

Location

Apex Research Of Riverside

Riverside, CA, United States, 92505

Location

Twin Cities Clinical Research

Brooklyn Center, MN, United States, 55430

Arms	Assigned Interventions
Active Comparator: Dapagliflozin (10 mg)	Drug: Dapagliflozin Tablets, Oral, 10 mg, Once Daily, 104 weeks Other Name: BMS-512148
Active Comparator: Dapagliflozin (5 mg)	Drug: Dapagliflozin Tablets, Oral, 5 mg, Once Daily, 104 weeks Other Name: BMS-512148
Placebo Comparator: Placebo	Drug: Placebo Tablets, Oral, 0 mg, Once Daily, 104 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
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.

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
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Participant Flow: Overall Study

	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
STARTED	84	83	85
COMPLETED	63	72	69
NOT COMPLETED	21	11	16
Lack of Efficacy	2	0	0
Adverse Event	12	7	6
Withdrawal by Subject	3	1	6
Death	1	0	1
Lost to Follow-up	0	1	0
non-compliance, not met criteria, etc.	3	2	3

Baseline Characteristics

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

All randomized participants who received at least 1 dose of study medication

Reporting Groups

	Description
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Baseline Measures

	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg	Total
Number of Participants [units: Participants]	84	83	85	252
Age Continuous [units: Years] Mean ± Standard Deviation	67 ± 8.6	66 ± 8.9	68 ± 7.7	67 ± 8.4
Age, Customized [units: Participants]
Younger than 65 years	36	39	29	104
65 years and older	48	44	56	148
Gender, Customized [units: Participants]
Male	53	55	56	164
Female	31	28	29	88
Race/Ethnicity, Customized [units: Participants]
WHITE	69	65	77	211
BLACK OR AFRICAN AMERICAN	1	7	4	12
ASIAN	6	4	3	13
OTHER	8	7	1	16
Weight [units: kg] Mean ± Standard Deviation	89.61 ± 20.046	95.23 ± 20.909	93.25 ± 17.309	92.69 ± 19.529
Pre-Enrollment Anti-Hyperglycemic Therapy [units: Participants]
INSULIN-BASED REGIMEN	55	54	55	164
SULFONYLUREA-BASED REGIMEN	21	21	21	63
THIAZOLIINEDIONE-BASED REGIMEN	1	1	2	4
OTHER REGIMEN	7	7	7	21

Outcome Measures

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

Measure Type	Primary
Measure Name	Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]
Measure 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
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.
All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)

Reporting Groups

	Description
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Measured Values

	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Number of Participants Analyzed [units:participants]	82	83	82
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF] [units: % of hemoglobin] Mean (Standard Error)	-0.32 (0.1701)	-0.41 (0.1701)	-0.44 (0.1708)

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

Groups^[1]	Placebo, Dapagliflozin 5 mg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.561
Mean Difference (Final Values)^[5]	-0.08
Standard Error of the mean	± 0.1448
95% Confidence Interval	( -0.37 to 0.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[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:
	Primary endpoints were tested at alpha=0.027 applying Dunnett’s adjustment
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]

Groups^[1]	Placebo, Dapagliflozin 10 mg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.435
Mean Difference (Final Values)^[5]	-0.11
Standard Error of the mean	± 0.1457
95% Confidence Interval	( -0.40 to 0.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[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:
	Primary endpoints were tested at alpha=0.027 applying Dunnett’s adjustment
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])
Measure 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
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.
All randomized participants who received study medication and had nonmissing FPG values at baseline and Week 24 (LOCF)

Reporting Groups

	Description
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Measured Values

	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Number of Participants Analyzed [units:participants]	83	83	85
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF]) [units: mg/dL] Mean (Standard Error)	8.4 (9.621)	-5.2 (9.548)	-0.6 (9.524)

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

Groups^[1]	Placebo, Dapagliflozin 5 mg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-13.6
Standard Error of the mean	± 8.142
95% Confidence Interval	( -29.7 to 2.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])

Groups^[1]	Placebo, Dapagliflozin 10 mg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-9.0
Standard Error of the mean	± 8.136
95% Confidence Interval	( -25.0 to 7.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])
Measure 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
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.
All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24 (LOCF)

Reporting Groups

	Description
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Measured Values

	Placebo	Dapagliflozin 5 mg	Dapagliflozin 10 mg
Number of Participants Analyzed [units:participants]	84	83	85
Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF]) [units: kg] Mean (Standard Error)	0.27 (0.4872)	-1.54 (0.4815)	-1.89 (0.4693)

Statistical Analysis 1 for Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])

Groups^[1]	Placebo, Dapagliflozin 5 mg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-1.81
Standard Error of the mean	± 0.4435
95% Confidence Interval	( -2.68 to -0.94 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

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

Groups^[1]	Placebo, Dapagliflozin 10 mg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-2.16
Standard Error of the mean	± 0.4395
95% Confidence Interval	( -3.03 to -1.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious 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.
Additional Description	No text entered.

Reporting Groups

	Description
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Serious Adverse Events

Placebo

Dapagliflozin 5 mg

Dapagliflozin 10 mg

Total, serious adverse events

# participants affected / at risk

9/84 (10.71%)

7/83 (8.43%)

12/85 (14.12%)

Metabolism and nutrition disorders

HYPOGLYCAEMIA¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

2/85 (2.35%)

# events

Metabolism and nutrition disorders

HYPERGLYCAEMIA¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Metabolism and nutrition disorders

HYPERKALAEMIA¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Nervous system disorders

CEREBRAL INFARCTION¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Nervous system disorders

SYNCOPE¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Cardiac disorders

MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Cardiac disorders

ACUTE MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

2/84 (2.38%)

0/83 (0.00%)

0/85 (0.00%)

# events

Cardiac disorders

CARDIAC FAILURE¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Cardiac disorders

CARDIOMYOPATHY¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Eye disorders

RETINAL DETACHMENT¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Infections and infestations

SEPTIC SHOCK¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Infections and infestations

CELLULITIS¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Infections and infestations

PNEUMONIA¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Investigations

HEART RATE INCREASED¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

PROSTATE CANCER¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Renal and urinary disorders

URINARY RETENTION¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Vascular disorders

HYPOTENSION¹,^†

# participants affected / at risk

0/84 (0.00%)

0/83 (0.00%)

1/85 (1.18%)

# events

Blood and lymphatic system disorders

ANAEMIA¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Gastrointestinal disorders

INGUINAL HERNIA¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

General disorders

CHEST PAIN¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

General disorders

OEDEMA¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

Immune system disorders

HYPERSENSITIVITY¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

Injury, poisoning and procedural complications

TRAUMATIC BRAIN INJURY¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

Musculoskeletal and connective tissue disorders

OSTEOARTHRITIS¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

Musculoskeletal and connective tissue disorders

SPONDYLOLISTHESIS¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Musculoskeletal and connective tissue disorders

TENDON DISORDER¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

Reproductive system and breast disorders

BALANOPOSTHITIS¹,^†

# participants affected / at risk

0/84 (0.00%)

1/83 (1.20%)

0/85 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

DYSPNOEA¹,^†

# participants affected / at risk

1/84 (1.19%)

0/83 (0.00%)

0/85 (0.00%)

# events

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

Other 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.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo	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)
Dapagliflozin 5 mg	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)
Dapagliflozin 10 mg	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)

Other Adverse Events

Placebo

Dapagliflozin 5 mg

Dapagliflozin 10 mg

Total, other (not including serious) adverse events

# participants affected / at risk

39/84 (46.43%)

45/83 (54.22%)

42/85 (49.41%)

Renal and urinary disorders

POLLAKIURIA¹,^†

# participants affected / at risk

3/84 (3.57%)

5/83 (6.02%)

10/85 (11.76%)

# events

Respiratory, thoracic and mediastinal disorders

COUGH¹,^†

# participants affected / at risk

2/84 (2.38%)

8/83 (9.64%)

8/85 (9.41%)

# events

Gastrointestinal disorders

DIARRHOEA¹,^†

# participants affected / at risk

3/84 (3.57%)

3/83 (3.61%)

8/85 (9.41%)

# events

Musculoskeletal and connective tissue disorders

MUSCULOSKELETAL PAIN¹,^†

# participants affected / at risk

3/84 (3.57%)

3/83 (3.61%)

7/85 (8.24%)

# events

Gastrointestinal disorders

NAUSEA¹,^†

# participants affected / at risk

1/84 (1.19%)

3/83 (3.61%)

7/85 (8.24%)

# events

Infections and infestations

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

3/84 (3.57%)

3/83 (3.61%)

6/85 (7.06%)

# events

Nervous system disorders

DIZZINESS¹,^†

# participants affected / at risk

4/84 (4.76%)

10/83 (12.05%)

5/85 (5.88%)

# events

Metabolism and nutrition disorders

HYPERKALAEMIA¹,^†

# participants affected / at risk

10/84 (11.90%)

7/83 (8.43%)

5/85 (5.88%)

# events

Vascular disorders

HYPERTENSION¹,^†

# participants affected / at risk

5/84 (5.95%)

1/83 (1.20%)

5/85 (5.88%)

# events

Infections and infestations

NASOPHARYNGITIS¹,^†

# participants affected / at risk

5/84 (5.95%)

6/83 (7.23%)

4/85 (4.71%)

# events

General disorders

OEDEMA PERIPHERAL¹,^†

# participants affected / at risk

4/84 (4.76%)

8/83 (9.64%)

4/85 (4.71%)

# events

Musculoskeletal and connective tissue disorders

ARTHRALGIA¹,^†

# participants affected / at risk

5/84 (5.95%)

5/83 (6.02%)

2/85 (2.35%)

# events

Musculoskeletal and connective tissue disorders

BACK PAIN¹,^†

# participants affected / at risk

6/84 (7.14%)

7/83 (8.43%)

2/85 (2.35%)

# events

Renal and urinary disorders

MICTURITION URGENCY¹,^†

# participants affected / at risk

0/84 (0.00%)

5/83 (6.02%)

2/85 (2.35%)

# events

Infections and infestations

GASTROENTERITIS¹,^†

# participants affected / at risk

5/84 (5.95%)

1/83 (1.20%)

1/85 (1.18%)

# events

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

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.

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
E-mail:	[email protected]

Documents available

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
Download
Publication
Download
Publication long-term
Download
MB102029_Redacted_CSR_synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Bristol-Myers Squibb

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Marin Endocrine Care & Research, Inc.

Office Of Richard Cherlin, Md

Low Country Internal Medicine Of Sc, Pa

Carolina Health Specialists

Cedar Research Llc

Aurora Advanced Healthcare

Apex Research Of Riverside

Twin Cities Clinical Research

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Publication

Publication long-term

MB102029_Redacted_CSR_synopsis

Trial Results Summaries