Trial Outcomes & Findings for A Study to Evaluate the Effect of Dapagliflozin on Blood Glucose Level and Renal Safety in Patients With Type 2 Diabetes (NCT NCT02413398)

Last Updated: 2018-10-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

321 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2018-10-31

Participant Flow

Participant milestones

Participant milestones
Measure	Dapagliflozin 10mg QD 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo QD Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Overall Study STARTED	160	161
Overall Study COMPLETED	156	154
Overall Study NOT COMPLETED	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Dapagliflozin 10mg QD 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo QD Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Overall Study Lost to Follow-up	2	4
Overall Study Withdrawal by Subject	1	1
Overall Study Other Eligibility criteria	1	2

Baseline Characteristics

159/160 subjects in the Dapaglifozin group had an enrolment UACR value.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dapagliflozin 10mg QD n=160 Participants 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo n=161 Participants Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks	Total n=321 Participants Total of all reporting groups
Age, Continuous	65.3 Years STANDARD_DEVIATION 6.22 • n=160 Participants	66.2 Years STANDARD_DEVIATION 6.49 • n=161 Participants	65.8 Years STANDARD_DEVIATION 6.36 • n=321 Participants
Age, Customized < 65 Years	64 Participants n=160 Participants	46 Participants n=161 Participants	110 Participants n=321 Participants
Age, Customized >= 65 Years	96 Participants n=160 Participants	115 Participants n=161 Participants	211 Participants n=321 Participants
Sex: Female, Male Female	69 Participants n=160 Participants	70 Participants n=161 Participants	139 Participants n=321 Participants
Sex: Female, Male Male	91 Participants n=160 Participants	91 Participants n=161 Participants	182 Participants n=321 Participants
Race/Ethnicity, Customized American Indian Or Alaska Native	2 Participants n=160 Participants	0 Participants n=161 Participants	2 Participants n=321 Participants
Race/Ethnicity, Customized Asian	5 Participants n=160 Participants	8 Participants n=161 Participants	13 Participants n=321 Participants
Race/Ethnicity, Customized Black Or African American	11 Participants n=160 Participants	12 Participants n=161 Participants	23 Participants n=321 Participants
Race/Ethnicity, Customized Other	1 Participants n=160 Participants	1 Participants n=161 Participants	2 Participants n=321 Participants
Race/Ethnicity, Customized White	141 Participants n=160 Participants	140 Participants n=161 Participants	281 Participants n=321 Participants
Body Mass Index	32.6 kg/m^2 STANDARD_DEVIATION 4.7 • n=160 Participants	31.6 kg/m^2 STANDARD_DEVIATION 5.0 • n=161 Participants	32.1 kg/m^2 STANDARD_DEVIATION 4.9 • n=321 Participants
Estimated Glomular Filtration Rate (eGFR)	51.8 mL/min/1.73 m^2 STANDARD_DEVIATION 4.1 • n=160 Participants	51.6 mL/min/1.73 m^2 STANDARD_DEVIATION 3.8 • n=161 Participants	51.7 mL/min/1.73 m^2 STANDARD_DEVIATION 3.9 • n=321 Participants
Urine Albumin-to-Creatinine Ratio (UACR)	226.91 mg/g STANDARD_DEVIATION 566.67 • n=159 Participants • 159/160 subjects in the Dapaglifozin group had an enrolment UACR value.	246.52 mg/g STANDARD_DEVIATION 775.49 • n=161 Participants • 159/160 subjects in the Dapaglifozin group had an enrolment UACR value.	236.78 mg/g STANDARD_DEVIATION 678.81 • n=320 Participants • 159/160 subjects in the Dapaglifozin group had an enrolment UACR value.

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: 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.

Outcome measures

Outcome measures
Measure	Dapagliflozin n=142 Participants 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo n=134 Participants Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24	-0.37 percent Standard Error 0.10	-0.03 percent Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, Week 24

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.

Outcome measures

Outcome measures
Measure	Dapagliflozin n=149 Participants 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo n=146 Participants Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24.	-3.42 percent change Standard Error 0.32	-2.02 percent change Standard Error 0.32

SECONDARY outcome

Timeframe: Baseline, Week 24

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.

Outcome measures

Outcome measures
Measure	Dapagliflozin n=135 Participants 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo n=134 Participants Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24.	-21.46 mg/dL Standard Error 5.20	-4.87 mg/dL Standard Error 5.13

SECONDARY outcome

Timeframe: Baseline, Week 24

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.

Outcome measures

Outcome measures
Measure	Dapagliflozin n=146 Participants 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo n=145 Participants Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24.	-4.8 mmHg Standard Error 1.5	-1.7 mmHg Standard Error 1.5

Adverse Events

Dapagliflozin 10mg QD

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Anna Maria Langkilde, MD PhD

Global Clinical Leader-Dapagliflozin AstraZeneca

Phone: Tel: + 46 31 7761000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dapagliflozin 10mg QD n=160 participants at risk 10 mg Tablets, Oral, Once daily, 24 weeks	Placebo n=161 participants at risk Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks
Cardiac disorders Acute coronary syndrome	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Cardiac disorders Acute myocardial infarction	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Cardiac disorders Angina pectoris	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Cardiac disorders Angina unstable	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 2 • 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).
Cardiac disorders Aortic valve incompetence	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Cardiac disorders Atrioventricular block	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Cardiac disorders Atrioventricular block complete	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Cardiac disorders Cardiac failure congestive	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Cardiac disorders Mitral valve incompetence	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Cardiac disorders Myocardial ischaemia	0.62% 1/160 • Number of events 2 • 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).	0.00% 0/161 • 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).
Gastrointestinal disorders Gingival bleeding	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Infections and infestations Diabetic gangrene	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Infections and infestations Gastroenteritis	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Infections and infestations Osteomyelitis chronic	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Nervous system disorders Cerebrovascular accident	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Nervous system disorders Ischaemic stroke	0.62% 1/160 • Number of events 1 • 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).	0.62% 1/161 • Number of events 1 • 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).
Nervous system disorders Syncope	0.62% 1/160 • Number of events 1 • 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).	0.00% 0/161 • 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).
Reproductive system and breast disorders Acquired hydrocele	0.00% 0/160 • 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).	0.62% 1/161 • Number of events 1 • 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).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.62% 1/160 • Number of events 1 • 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).	0.62% 1/161 • Number of events 1 • 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).