Trial Outcomes & Findings for A Study to Investigate Effects of Omega-3 Carboxylic Acids and Dapagliflozin on Liver Fat Content in Diabetic Patients (NCT NCT02279407)
NCT ID: NCT02279407
Last Updated: 2017-03-17
Results Overview
To evaluate the efficacy of the combination therapy (Epanova + Dapagliflozin) when compared to placebo with respect to reduction in liver fat content (%) at the end of 12 weeks of double-blinded treatment. Treatment effect in liver fat reduction (%) was assessed using a mixed linear model with the change from baseline on logarithmic scale as response variable and the logarithm of the baseline value as covariate, treatment as fixed effect, and center as random effect. The treatment effect was then back-transformed to original scale as Geometric mean ratio and presented as percentage change from baseline.
COMPLETED
PHASE2
223 participants
12 weeks
2017-03-17
Participant Flow
This study was conducted in 5 centers in Sweden between 20 January 2015 and 11 December 2015.
The study duration was up to 15 weeks: an screening period of up to 2 weeks, a 12-week treatment period, and a follow-up visit 1 week after the last dose of study drug. A total of 223 patients signed informed consent; data was not recorded for 1 patient and 18 were screened twice. Therefore, 204 patients were screened, and 84 were randomized.
Participant milestones
| Measure |
Epanova + Dapagliflozin
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Dapagliflozin
Dapagliflozin 10 mg/day + placebo to Epanova
|
Epanova
Epanova 4 g/day + placebo to Dapagliflozin
|
Placebo
Placebo to Epanova and placebo to Dapagliflozin
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
22
|
21
|
20
|
21
|
|
Overall Study
COMPLETED
|
20
|
20
|
15
|
20
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
5
|
1
|
Reasons for withdrawal
| Measure |
Epanova + Dapagliflozin
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Dapagliflozin
Dapagliflozin 10 mg/day + placebo to Epanova
|
Epanova
Epanova 4 g/day + placebo to Dapagliflozin
|
Placebo
Placebo to Epanova and placebo to Dapagliflozin
|
|---|---|---|---|---|
|
Overall Study
Couldn't swallow IP; noncompliance
|
0
|
0
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
1
|
|
Overall Study
Adverse Event
|
1
|
1
|
2
|
0
|
Baseline Characteristics
A Study to Investigate Effects of Omega-3 Carboxylic Acids and Dapagliflozin on Liver Fat Content in Diabetic Patients
Baseline characteristics by cohort
| Measure |
Epanova + Dapagliflozin
n=22 Participants
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Epanova
n=20 Participants
Epanova 4 g/day + placebo to Dapagliflozin
|
Dapagliflozin
n=21 Participants
Dapagliflozin 10 mg/day + placebo to Epanova
|
Placebo
n=21 Participants
Placebo to Epanova and placebo to Dapagliflozin
|
Total
n=84 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
65.0 Years
STANDARD_DEVIATION 5.42 • n=5 Participants
|
66.2 Years
STANDARD_DEVIATION 5.94 • n=7 Participants
|
65.0 Years
STANDARD_DEVIATION 6.54 • n=5 Participants
|
65.6 Years
STANDARD_DEVIATION 6.10 • n=4 Participants
|
65.5 Years
STANDARD_DEVIATION 5.92 • n=21 Participants
|
|
Age, Customized
<50
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Age, Customized
>=50 - <65
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Age, Customized
>=65
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
56 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
59 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black Or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
21 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
82 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The Full Analysis Set included all randomized patients, regardless of whether they took trial medication or not. In this set, patients were analyzed according to their randomized treatment assignment.
To evaluate the efficacy of the combination therapy (Epanova + Dapagliflozin) when compared to placebo with respect to reduction in liver fat content (%) at the end of 12 weeks of double-blinded treatment. Treatment effect in liver fat reduction (%) was assessed using a mixed linear model with the change from baseline on logarithmic scale as response variable and the logarithm of the baseline value as covariate, treatment as fixed effect, and center as random effect. The treatment effect was then back-transformed to original scale as Geometric mean ratio and presented as percentage change from baseline.
Outcome measures
| Measure |
Epanova + Dapagliflozin
n=20 Participants
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Placebo
n=19 Participants
Placebo to Epanova and placebo to Dapagliflozin
|
Epanova
Epanova 4 g/day + placebo to Dapagliflozin
|
|---|---|---|---|
|
Change From Baseline to Week 12 in % Liver Fat as Assessed by MRI (Comparison Versus Placebo)
|
0.79 ratio of % liver fat
Interval 0.69 to 0.9
|
0.97 ratio of % liver fat
Interval 0.9 to 1.04
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The Full Analysis Set included all randomized patients, regardless of whether they took trial medication or not. In this set, patients were analyzed according to their randomized treatment assignment.
To evaluate the relative efficacy of the combination of Epanova and dapagliflozin versus Epanova alone and dapagliflozin alone with respect to reduction in % liver fat at the end of 12 weeks of double-blind treatment. Treatment effect in liver fat reduction (%) was assessed using a mixed linear model with the change from baseline on logarithmic scale as response variable and the logarithm of the baseline value as covariate, treatment as fixed effect, and center as random effect. The treatment effect was then back-transformed to original scale as Geometric mean ratio and presented as percentage change from baseline.
Outcome measures
| Measure |
Epanova + Dapagliflozin
n=20 Participants
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Placebo
n=19 Participants
Placebo to Epanova and placebo to Dapagliflozin
|
Epanova
n=15 Participants
Epanova 4 g/day + placebo to Dapagliflozin
|
|---|---|---|---|
|
Change From Baseline to Week 12 in % Liver Fat (Comparison Between Active Treatment Groups)
|
0.79 ratio of % liver fat
Interval 0.69 to 0.9
|
0.87 ratio of % liver fat
Interval 0.77 to 0.99
|
0.85 ratio of % liver fat
Interval 0.78 to 0.92
|
Adverse Events
Epanova + Dapagliflozin
Epanova
Dapagliflozin
Placebo
Serious adverse events
| Measure |
Epanova + Dapagliflozin
n=22 participants at risk
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Epanova
n=20 participants at risk
Epanova 4 g/day + placebo to Dapagliflozin
|
Dapagliflozin
n=21 participants at risk
Dapagliflozin 10 mg/day + placebo to Epanova
|
Placebo
n=21 participants at risk
Placebo to Epanova and placebo to Dapagliflozin
|
|---|---|---|---|---|
|
Infections and infestations
Sepsis
|
0.00%
0/22
|
0.00%
0/20
|
0.00%
0/21
|
4.8%
1/21 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/22
|
0.00%
0/20
|
4.8%
1/21 • Number of events 1
|
0.00%
0/21
|
Other adverse events
| Measure |
Epanova + Dapagliflozin
n=22 participants at risk
Epanova 4 g/day + Dapagliflozin 10 mg/day
|
Epanova
n=20 participants at risk
Epanova 4 g/day + placebo to Dapagliflozin
|
Dapagliflozin
n=21 participants at risk
Dapagliflozin 10 mg/day + placebo to Epanova
|
Placebo
n=21 participants at risk
Placebo to Epanova and placebo to Dapagliflozin
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
13.6%
3/22 • Number of events 3
|
10.0%
2/20 • Number of events 2
|
0.00%
0/21
|
0.00%
0/21
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
9.5%
2/21 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
11/22 • Number of events 12
|
35.0%
7/20 • Number of events 7
|
4.8%
1/21 • Number of events 1
|
0.00%
0/21
|
|
Gastrointestinal disorders
Nausea
|
9.1%
2/22 • Number of events 2
|
15.0%
3/20 • Number of events 3
|
0.00%
0/21
|
9.5%
2/21 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
9.1%
2/22 • Number of events 2
|
10.0%
2/20 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
4.8%
1/21 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
9.1%
2/22 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
23.8%
5/21 • Number of events 5
|
4.8%
1/21 • Number of events 1
|
|
Nervous system disorders
Headache
|
4.5%
1/22 • Number of events 1
|
0.00%
0/20
|
0.00%
0/21
|
9.5%
2/21 • Number of events 2
|
|
Renal and urinary disorders
Pollakiuria
|
9.1%
2/22 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
9.5%
2/21 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place