Trial Outcomes & Findings for Phase IV Study With a 36-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Japanese Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin. (NCT NCT02157298)
NCT ID: NCT02157298
Last Updated: 2016-05-11
Results Overview
Mean change in HbA1c levels from baseline to Week 16 between dapagliflozin 5 mg versus placebo
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
266 participants
Primary outcome timeframe
Baseline to Week 16
Results posted on
2016-05-11
Participant Flow
First participant enrolled: 06-Jun-2014; Last participant last visit of ST period: 02-Feb-2015; 266 participants were enrolled in 20 Japanese centers. 183 Japanese men or women aged \>=20 years with inadequate glycemic control (HbA1c levels of \>=7.2% to \<11.0%) with diet, exercise and on stable dose of insulin +/- DPP-4 inhibitor were treated.
A 8-week wash-out period was applicable only for participants on ongoing anti-diabetic treatment at enrollment. A 2-week lead-in period was applicable for all participants.
Participant milestones
| Measure |
Dapagliflozin
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Overall Study
STARTED
|
123
|
60
|
|
Overall Study
COMPLETED
|
119
|
58
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
Reasons for withdrawal
| Measure |
Dapagliflozin
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Subject no longer meets study criteria
|
1
|
2
|
|
Overall Study
Poor/Non-compliance
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Phase IV Study With a 36-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Japanese Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin.
Baseline characteristics by cohort
| Measure |
Dapagliflozin
n=122 Participants
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=60 Participants
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
Total
n=182 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.3 years
STANDARD_DEVIATION 9.83 • n=5 Participants
|
57.6 years
STANDARD_DEVIATION 9.86 • n=7 Participants
|
58.0 years
STANDARD_DEVIATION 9.82 • n=5 Participants
|
|
Age, Customized
<=65 years
|
84 participants
n=5 Participants
|
43 participants
n=7 Participants
|
127 participants
n=5 Participants
|
|
Age, Customized
Between 65 and 75 years
|
37 participants
n=5 Participants
|
16 participants
n=7 Participants
|
53 participants
n=5 Participants
|
|
Age, Customized
>=75 years
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
89 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
122 participants
n=5 Participants
|
60 participants
n=7 Participants
|
182 participants
n=5 Participants
|
|
Body Weight
|
73.90 kg
STANDARD_DEVIATION 15.663 • n=5 Participants
|
71.89 kg
STANDARD_DEVIATION 13.430 • n=7 Participants
|
73.24 kg
STANDARD_DEVIATION 14.956 • n=5 Participants
|
|
Body Mass Index
|
26.89 kg/m^2
STANDARD_DEVIATION 4.930 • n=5 Participants
|
26.12 kg/m^2
STANDARD_DEVIATION 3.485 • n=7 Participants
|
26.64 kg/m^2
STANDARD_DEVIATION 4.510 • n=5 Participants
|
|
Waist Circumference
|
93.2 cm
STANDARD_DEVIATION 11.83 • n=5 Participants
|
92.3 cm
STANDARD_DEVIATION 9.00 • n=7 Participants
|
92.9 cm
STANDARD_DEVIATION 10.96 • n=5 Participants
|
|
HbA1c
|
8.26 percent of hemoglobin glycosylated
STANDARD_DEVIATION 0.792 • n=5 Participants
|
8.52 percent of hemoglobin glycosylated
STANDARD_DEVIATION 0.937 • n=7 Participants
|
8.34 percent of hemoglobin glycosylated
STANDARD_DEVIATION 0.849 • n=5 Participants
|
|
Fasting Plasma Glucose
|
160.70 mg/dL
STANDARD_DEVIATION 44.948 • n=5 Participants
|
159.68 mg/dL
STANDARD_DEVIATION 38.001 • n=7 Participants
|
160.36 mg/dL
STANDARD_DEVIATION 42.679 • n=5 Participants
|
|
Calculated Mean Daily Insulin Dose
|
37.87 IU/Day
STANDARD_DEVIATION 18.033 • n=5 Participants
|
40.58 IU/Day
STANDARD_DEVIATION 16.764 • n=7 Participants
|
38.76 IU/Day
STANDARD_DEVIATION 17.625 • n=5 Participants
|
|
DPP-4 Inhibitor Usage
Yes
|
54 participants
n=5 Participants
|
27 participants
n=7 Participants
|
81 participants
n=5 Participants
|
|
DPP-4 Inhibitor Usage
No
|
68 participants
n=5 Participants
|
33 participants
n=7 Participants
|
101 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 16Population: Full Analysis Set, participants with non-missing baseline and at least one post-baseline value up to week 16
Mean change in HbA1c levels from baseline to Week 16 between dapagliflozin 5 mg versus placebo
Outcome measures
| Measure |
Dapagliflozin
n=122 Participants
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=59 Participants
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Adjusted Mean Change in HbA1c Levels
|
-0.55 percentage of hemoglobin glycosylated
Interval -0.67 to -0.42
|
0.05 percentage of hemoglobin glycosylated
Interval -0.13 to 0.23
|
SECONDARY outcome
Timeframe: Baseline to Week 16Population: Full Analysis Set, participants with non-missing baseline and at least one post-baseline value up to week 16
Mean change in fasting plasma glucose from baseline to Week 16 between dapagliflozin 5 mg versus placebo
Outcome measures
| Measure |
Dapagliflozin
n=121 Participants
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=59 Participants
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Fasting Plasma Glucose
|
-21.7 mg/dL
Interval -28.3 to -15.1
|
1.0 mg/dL
Interval -8.4 to 10.3
|
SECONDARY outcome
Timeframe: Baseline to Week 16Population: Full Analysis Set, participants with non-missing baseline and at least one post-baseline value up to week 16
Mean change in total body weight from baseline to Week 16 between dapagliflozin 5 mg versus placebo
Outcome measures
| Measure |
Dapagliflozin
n=122 Participants
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=59 Participants
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Total Body Weight
|
-0.6 kg
Interval -0.9 to -0.2
|
0.7 kg
Interval 0.2 to 1.1
|
SECONDARY outcome
Timeframe: Baseline to Week 16Population: Full Analysis Set, participants with non-missing baseline and at least one post-baseline value up to week 16
Mean change in calculated mean daily insulin dose from baseline to Week 16 between dapagliflozin 5 mg versus placebo
Outcome measures
| Measure |
Dapagliflozin
n=121 Participants
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=60 Participants
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Total Mean Daily Insulin Dose
|
-0.74 IU/Day
Interval -1.21 to -0.27
|
-0.02 IU/Day
Interval -0.68 to 0.64
|
SECONDARY outcome
Timeframe: Baseline to Week 16Population: Full Analysis Set, participants with non-missing baseline and Week 16 (LOCF) value
Proportion of participants with mean daily insulin dose reduction greater than or equal 10% from baseline to week 16 (LOCF) between dapagliflozin 5 mg versus placebo
Outcome measures
| Measure |
Dapagliflozin
n=121 Participants
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=60 Participants
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Proportion of Participants With Mean Daily Insulin Dose Reduction of Greater Than or Equal 10%
|
8.2 percentage of participants
Interval 3.3 to 13.1
|
4.9 percentage of participants
Interval -0.7 to 10.4
|
Adverse Events
Dapagliflozin
Serious events: 3 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dapagliflozin
n=123 participants at risk
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=60 participants at risk
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Hepatobiliary disorders
Cholelithiasis
|
0.81%
1/123 • Number of events 1 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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%
0/60 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.81%
1/123 • Number of events 1 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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%
0/60 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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
Osteochondrosis
|
0.81%
1/123 • Number of events 1 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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%
0/60 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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 |
Dapagliflozin
n=123 participants at risk
Dapagliflozin 5 mg plus insulin alone or in combination with DPP-4 inhibitor
|
Placebo
n=60 participants at risk
Placebo plus insulin alone or in combination with DPP-4 inhibitor
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
10.6%
13/123 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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.
|
11.7%
7/60 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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
Pollakiuria
|
8.9%
11/123 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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.
|
5.0%
3/60 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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.
|
|
Gastrointestinal disorders
Constipation
|
2.4%
3/123 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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.
|
5.0%
3/60 • Non-serious/serious adverse events on or after the first date of double-blind treatment and on or prior to the last day plus 4/30 days or up to follow-up visit if earlier, or up to and excluding the start date of open-label extension period if earlier.
Participants were questioned at each study 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