Trial Outcomes & Findings for Evaluation of Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Background Combination of Metformin and Sulfonylurea (NCT NCT01392677)
NCT ID: NCT01392677
Last Updated: 2014-03-12
Results Overview
To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
311 participants
Primary outcome timeframe
Baseline to week 24
Results posted on
2014-03-12
Participant Flow
First participant enrolled: 24 Oct 2011. Last participant completed 24 week period: 07 Jan 2013. 311 participants were enrolled, 219 were randomized in 45 centers in 5 European countries and in North America. Men and women aged \>= 18 years with inadequate glycemic control (HbA1c 7.0% to 10.5% prior to randomization).
During enrollment, diet and life-style advice was given to participants and was reinforced during a placebo lead-in period. Dose of anti-hyperglycemic combination therapy of metformin \>= 1500 mg/day and maximum tolerated dose which must be at least half the maximum dose of sulfonylurea for at least 8 weeks prior to enrollment were to remain stable.
Participant milestones
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Overall Study
STARTED
|
109
|
109
|
|
Overall Study
COMPLETED
|
101
|
101
|
|
Overall Study
NOT COMPLETED
|
8
|
8
|
Reasons for withdrawal
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Incorrect enrollment
|
2
|
3
|
|
Overall Study
Other reason
|
3
|
2
|
Baseline Characteristics
Evaluation of Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Background Combination of Metformin and Sulfonylurea
Baseline characteristics by cohort
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=108 Participants
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=108 Participants
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
Total
n=216 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.9 Years
STANDARD_DEVIATION 9.24 • n=93 Participants
|
61.1 Years
STANDARD_DEVIATION 9.65 • n=4 Participants
|
61.0 Years
STANDARD_DEVIATION 9.42 • n=27 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=93 Participants
|
62 Participants
n=4 Participants
|
110 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
106 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
102 Participants
n=93 Participants
|
104 Participants
n=4 Participants
|
206 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Body Weight
|
90.07 kg
STANDARD_DEVIATION 16.175 • n=93 Participants
|
88.57 kg
STANDARD_DEVIATION 17.584 • n=4 Participants
|
89.32 kg
STANDARD_DEVIATION 16.872 • n=27 Participants
|
|
Body Mass Index
|
32.02 kg/m^2
STANDARD_DEVIATION 4.581 • n=93 Participants
|
31.93 kg/m^2
STANDARD_DEVIATION 4.840 • n=4 Participants
|
31.97 kg/m^2
STANDARD_DEVIATION 4.702 • n=27 Participants
|
|
Glycosylated hemoglobin A1c (HbA1c)
|
8.24 Percent
STANDARD_DEVIATION 0.865 • n=93 Participants
|
8.08 Percent
STANDARD_DEVIATION 0.912 • n=4 Participants
|
8.16 Percent
STANDARD_DEVIATION 0.890 • n=27 Participants
|
|
Fasting Plasma Glucose
|
180.2 mg/dL
STANDARD_DEVIATION 43.13 • n=93 Participants
|
167.4 mg/dL
STANDARD_DEVIATION 43.32 • n=4 Participants
|
173.8 mg/dL
STANDARD_DEVIATION 43.61 • n=27 Participants
|
|
Fasting C-Peptide
|
2.5 ng/mL
STANDARD_DEVIATION 0.98 • n=93 Participants
|
2.5 ng/mL
STANDARD_DEVIATION 1.06 • n=4 Participants
|
2.5 ng/mL
STANDARD_DEVIATION 1.02 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline to week 24Population: Full Analysis Set, participants with non-missing baseline and week 24 values
To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.
Outcome measures
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=108 Participants
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=108 Participants
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Adjusted Mean Change From Baseline in HbA1c Levels
|
-0.17 Percent
Interval -0.31 to -0.02
|
-0.86 Percent
Interval -1.0 to -0.72
|
SECONDARY outcome
Timeframe: Baseline to week 24Population: Full Analysis Set, participants with non-missing baseline and week 24 (LOCF) values
To compare the change from baseline in fasting plasma glucose (FPG) to week 24 (LOCF) between dapagliflozin and placebo
Outcome measures
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=107 Participants
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=108 Participants
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Adjusted Mean Change From Baseline in FPG
|
-0.78 mg/dL
Interval -7.56 to 6.01
|
-34.23 mg/dL
Interval -40.98 to -27.48
|
SECONDARY outcome
Timeframe: Baseline to week 24Population: Full Analysis Set, participants with non-missing baseline and week 24 (LOCF) values
To compare the change from baseline in total body weight to week 24 (LOCF) between dapagliflozin and placebo
Outcome measures
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=108 Participants
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=108 Participants
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Total Body Weight
|
-0.58 kg
Interval -1.09 to -0.07
|
-2.65 kg
Interval -3.16 to -2.14
|
SECONDARY outcome
Timeframe: Baseline to week 24Population: Full Analysis Set, participants with non-missing baseline and week 24 (LOCF) values
To compare the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, at week 24 (LOCF) between dapagliflozin and placebo
Outcome measures
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=108 Participants
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=108 Participants
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Proportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)
|
11.1 Percentage of participants
Interval 5.4 to 16.8
|
31.8 Percentage of participants
Interval 23.3 to 40.2
|
SECONDARY outcome
Timeframe: Baseline to week 8Population: Full Analysis Set, participants with non-missing baseline and week 8 (LOCF) values
To compare the change from baseline in seated systolic blood pressure (SBP) to week 8 (LOCF) between dapagliflozin and placebo
Outcome measures
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=105 Participants
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=105 Participants
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure
|
-0.27 mmHg
Interval -2.6 to 2.05
|
-4.04 mmHg
Interval -6.36 to -1.72
|
Adverse Events
Placebo Plus Metformin Plus Sulfonylurea
Serious events: 6 serious events
Other events: 7 other events
Deaths: 0 deaths
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=109 participants at risk
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=109 participants at risk
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Cardiac disorders
aortic valve stenosis
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Cardiac disorders
arrhythmia
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Infections and infestations
diabetic gangrene
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Musculoskeletal and connective tissue disorders
sympathetic posterior cervical syndrome
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
renal cell carcinoma
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Renal and urinary disorders
calculus ureteric
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Respiratory, thoracic and mediastinal disorders
chronic obstructive pulmonary disease
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
|
Vascular disorders
peripheral arterial occlusive disease
|
0.92%
1/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
0.00%
0/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
Other adverse events
| Measure |
Placebo Plus Metformin Plus Sulfonylurea
n=109 participants at risk
Placebo once daily plus background combination of metformin and sulfonylurea
|
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
n=109 participants at risk
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
|
|---|---|---|
|
Infections and infestations
urinary tract infection
|
6.4%
7/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
4.6%
5/109 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER