trial to evaluate the efficacy and safety of dapagliflozin in Japanese type 2 diabetes mellitus patients

Study identifier:D1692C00005

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A multicenter, randomized, double-blind, placebo-controlled, parallel group, Phase 2 trial to evaluate the efficacy and safety of dapagliflozin as monotherapy in Japanese subjects with type 2 diabetes mellitus who have inadequate glycemic control

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 2

Healthy volunteers

Study drug

Dapagliflozin, Placebo

Sex

All

Actual Enrollment

417

Study type

Interventional

Age

18 Years - 79 Years

Date

Study Start Date: 01 Aug 2009

Primary Completion Date: 01 May 2010

Study Completion Date: 01 May 2010

Study design

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

Verification:

Verified 01 Aug 2013 by AstraZeneca

Collaborators

Bristol-Myers Squibb

Inclusion and exclusion criteria

Location

Research Site

Anjyo, Japan

Location

Research Site

Bunkyo-ku, Japan

Location

Research Site

Chuo-ku, Japan

Location

Research Site

Daito, Japan

Location

Research Site

Kamagaya, Japan

Location

Research Site

Kashiwara, Japan

Location

Research Site

Matsuyama, Japan

Location

Research Site

Nagoya, Japan

Arms	Assigned Interventions
Experimental: 1 1mg dapagliflozin	Drug: Dapagliflozin once daily, 12 weeks
Experimental: 2 2.5mg dapagliflozin	Drug: Dapagliflozin once daily, 12 weeks
Experimental: 3 5mg dapagliflozin	Drug: Dapagliflozin once daily, 12 weeks
Experimental: 4 10mg dapagliflozin	Drug: Dapagliflozin once daily, 12 weeks
Placebo Comparator: 5 Placebo	Drug: Placebo once daily, 12 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
Enrollment: 417; randomized: 279 Study Start Date: August 2009 Study Completion Date: May 2010 Primary Completion Date: May 2010

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
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Participant Flow: Overall Study

	1mg Dapagliflozin	2.5mg Dapagliflozin	5mg Dapagliflozin	10mg Dapagliflozin	Placebo
STARTED	59	56	58	52	54
COMPLETED	54	51	56	52	45
NOT COMPLETED	5	5	2	0	9
Incorrect Enrolment	1	0	0	0	0
Adverse Event	0	1	1	0	0
Subject No Longer Meets Study Criteria	2	2	0	0	5
Withdrawal by Subject	1	2	1	0	1
Safety	0	0	0	0	1
Death	1	0	0	0	0
Various	0	0	0	0	2

Baseline Characteristics

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

Full Analysis Set defined as all randomised participants (as randomized) who received at least one dose of double-blind study medication, who have a non-missing baseline value and at least one post-baseline efficacy value for at least one efficacy variable during double-blind period.

Reporting Groups

	Description
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Baseline Measures

	1mg Dapagliflozin	2.5mg Dapagliflozin	5mg Dapagliflozin	10mg Dapagliflozin	Placebo	Total
Number of Participants [units: Participants]	59	56	58	52	54	279
Age Continuous [units: years] Mean ± Standard Deviation	55.9 ± 9.73	57.7 ± 9.33	58.0 ± 9.50	56.5 ± 11.47	58.4 ± 9.97	57.3 ± 9.98
Gender, Male/Female [units: Participants]
Female	12	17	11	13	11	64
Male	47	39	47	39	43	215
Race/Ethnicity, Customized [units: Participants]	59	56	58	52	54	279
HBA1C [units: percent] Mean ± Standard Deviation	8.10 ± 0.785	7.92 ± 0.740	8.05 ± 0.660	8.18 ± 0.690	8.12 ± 0.714	8.07 ± 0.720

Outcome Measures

1. Primary Outcome Measure: Adjusted mean change in HbA1c levels [ Time Frame: Baseline to Week 12 ]

Measure Type	Primary
Measure Name	Adjusted mean change in HbA1c levels
Measure Description	The primary efficacy endpoint is the absolute change in HbA1c from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available.
Time Frame	Baseline to Week 12
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.
Full Analysis Set, participants with non-missing baseline and Week 12 (LOCF) values

Reporting Groups

	Description
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Measured Values

	1mg Dapagliflozin	2.5mg Dapagliflozin	5mg Dapagliflozin	10mg Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	59	54	58	52	52
Adjusted mean change in HbA1c levels [units: percent] Least Squares Mean (95% Confidence Interval)	-0.12 (-0.25 to 0.01)	-0.10 (-0.24 to 0.04)	-0.37 (-0.50 to -0.23)	-0.44 (-0.58 to -0.29)	0.35 (0.21 to 0.49)

Statistical Analysis 1 for Adjusted mean change in HbA1c levels

Groups^[1]	1mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.47
Standard Error of the mean	± 0.0987
95% Confidence Interval	( -0.67 to -0.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean change in HbA1c levels

Groups^[1]	2.5mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.45
Standard Error of the mean	± 0.1009
95% Confidence Interval	( -0.65 to -0.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Adjusted mean change in HbA1c levels

Groups^[1]	5mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.72
Standard Error of the mean	± 0.0990
95% Confidence Interval	( -0.92 to -0.53 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Adjusted mean change in HbA1c levels

Groups^[1]	10mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.79
Standard Error of the mean	± 0.1018
95% Confidence Interval	( -0.99 to -0.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Adjusted mean change in fasting plasma glucose [ Time Frame: Baseline to Week 12 ]

Measure Type	Secondary
Measure Name	Adjusted mean change in fasting plasma glucose
Measure Description	Change in fasting plasma glucose from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available.
Time Frame	Baseline to Week 12
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.
Full Analysis Set, participants with non-missing baseline and Week 12 (LOCF) values

Reporting Groups

	Description
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Measured Values

	1mg Dapagliflozin	2.5mg Dapagliflozin	5mg Dapagliflozin	10mg Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	50	52	51	47	50
Adjusted mean change in fasting plasma glucose [units: mg/dL] Least Squares Mean (95% Confidence Interval)	-16.63 (-23.25 to -10.00)	-19.97 (-26.47 to -13.47)	-23.49 (-30.06 to -16.93)	-31.92 (-38.76 to -25.09)	9.45 (2.82 to 16.08)

Statistical Analysis 1 for Adjusted mean change in fasting plasma glucose

Groups^[1]	1mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-26.08
Standard Error of the mean	± 4.7589
95% Confidence Interval	( -35.45 to -16.70 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted mean change in fasting plasma glucose

Groups^[1]	2.5mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-29.42
Standard Error of the mean	± 4.7100
95% Confidence Interval	( -38.70 to -20.14 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Adjusted mean change in fasting plasma glucose

Groups^[1]	5mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-32.94
Standard Error of the mean	± 4.7402
95% Confidence Interval	( -42.28 to -23.60 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Adjusted mean change in fasting plasma glucose

Groups^[1]	10mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-41.37
Standard Error of the mean	± 4.8358
95% Confidence Interval	( -50.90 to -31.85 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Proportion of participants achieving glycemic response defined as HbA1c <7% [ Time Frame: At Week 12 ]

Measure Type	Secondary
Measure Name	Proportion of participants achieving glycemic response defined as HbA1c <7%
Measure Description	Proportion of participants achieving therapeutic glycemic response defined as glycosylated hemoglobin <7%, after 12 weeks of double-blind therapy
Time Frame	At Week 12
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.
Full Analysis Set, participants with non-missing baseline and week 12 (LOCF) values

Reporting Groups

	Description
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Measured Values

	1mg Dapagliflozin	2.5mg Dapagliflozin	5mg Dapagliflozin	10mg Dapagliflozin	Placebo
Number of Participants Analyzed [units:participants]	59	54	58	52	52
Proportion of participants achieving glycemic response defined as HbA1c <7% [units: Percentage of participants]	1.7	9.3	5.2	9.6	1.9

Statistical Analysis 1 for Proportion of participants achieving glycemic response defined as HbA1c <7%

Groups^[1]	1mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	1.0000
Risk Difference (RD)^[5]	-0.2
95% Confidence Interval	( -9.1 to 7.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
[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:
	not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Proportion of participants achieving glycemic response defined as HbA1c <7%

Groups^[1]	2.5mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	0.2057
Risk Difference (RD)^[5]	7.3
95% Confidence Interval	( -2.3 to 18.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
[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:
	not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Proportion of participants achieving glycemic response defined as HbA1c <7%

Groups^[1]	5mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	0.6203
Risk Difference (RD)^[5]	3.2
95% Confidence Interval	( -6.2 to 13.2 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
[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:
	not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Proportion of participants achieving glycemic response defined as HbA1c <7%

Groups^[1]	10mg Dapagliflozin, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	0.2050
Risk Difference (RD)^[5]	7.7
95% Confidence Interval	( -2.0 to 19.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
[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:
	not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 12-week double-blind treatment plus 4/30 days or up to the follow-up visit if earlier.
Additional Description	Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at the study visit was assessed in comparison to the status at study entry.

Reporting Groups

	Description
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Serious Adverse Events

1mg Dapagliflozin

2.5mg Dapagliflozin

5mg Dapagliflozin

10mg Dapagliflozin

Placebo

Total, serious adverse events

# participants affected / at risk

2/59 (3.39%)

1/56 (1.79%)

2/58 (3.45%)

1/52 (1.92%)

0/54 (0.00%)

Cardiac disorders

ACUTE MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

1/58 (1.72%)

0/52 (0.00%)

0/54 (0.00%)

General disorders

MULTI-ORGAN FAILURE¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/58 (0.00%)

0/52 (0.00%)

0/54 (0.00%)

Hepatobiliary disorders

CHOLECYSTITIS¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/58 (0.00%)

0/52 (0.00%)

0/54 (0.00%)

Infections and infestations

GASTROENTERITIS¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

0/58 (0.00%)

1/52 (1.92%)

0/54 (0.00%)

Infections and infestations

SEPSIS¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/58 (0.00%)

0/52 (0.00%)

0/54 (0.00%)

Injury, poisoning and procedural complications

SPINAL COMPRESSION FRACTURE¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/58 (0.00%)

0/52 (0.00%)

0/54 (0.00%)

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

BLADDER CANCER¹,^†

# participants affected / at risk

0/59 (0.00%)

1/56 (1.79%)

0/58 (0.00%)

0/52 (0.00%)

0/54 (0.00%)

Skin and subcutaneous tissue disorders

DERMAL CYST¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

1/58 (1.72%)

0/52 (0.00%)

0/54 (0.00%)

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

Other Adverse Events

Time Frame	Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 12-week double-blind treatment plus 4/30 days or up to the follow-up visit if earlier.
Additional Description	Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at the study visit was assessed in comparison to the status at study entry.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
1mg Dapagliflozin	Dapagliflozin tablet 1 mg once daily
2.5mg Dapagliflozin	Dapagliflozin tablet 2.5 mg once daily
5mg Dapagliflozin	Dapagliflozin tablet 5 mg once daily
10mg Dapagliflozin	Dapagliflozin tablet 10 mg once daily
Placebo	Placebo Comparator

Other Adverse Events

1mg Dapagliflozin

2.5mg Dapagliflozin

5mg Dapagliflozin

10mg Dapagliflozin

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

14/59 (23.73%)

13/56 (23.21%)

14/58 (24.14%)

13/52 (25.00%)

14/54 (25.93%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

3/59 (5.08%)

0/56 (0.00%)

2/58 (3.45%)

0/52 (0.00%)

1/54 (1.85%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

12/59 (20.34%)

10/56 (17.86%)

7/58 (12.07%)

12/52 (23.08%)

13/54 (24.07%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/59 (0.00%)

3/56 (5.36%)

2/58 (3.45%)

1/52 (1.92%)

0/54 (0.00%)

Respiratory, thoracic and mediastinal disorders

Upper Respiratory Tract Inflammation¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

3/58 (5.17%)

0/52 (0.00%)

0/54 (0.00%)

Skin and subcutaneous tissue disorders

Eczema¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

0/58 (0.00%)

0/52 (0.00%)

3/54 (5.56%)

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

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
If an efficacy measurement was unavailable at the time point for analysis, last observation was carried forward (LOCF).

Results Point of Contact

Name/Title:	Eva Johnsson
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

CSR-D1692C00005.pdf
Download
D1692C00005 Clinical Study Protocol
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Parikh Shamik

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR-D1692C00005.pdf

D1692C00005 Clinical Study Protocol

Trial Results Summaries