Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Investigate Effects of Omega-3 Carboxylic Acids and Dapagliflozin on Liver Fat Content in Diabetic Patients (EFFECTII)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02279407
Recruitment Status : Completed
First Posted : October 31, 2014
Results First Posted : January 27, 2017
Last Update Posted : March 17, 2017
Sponsor:
Collaborator:
Uppsala Clinical Research, Uppsala, Sweden
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition T2 Diabetes and Fatty Liver Disease (Non-alcoholic Origin)
Interventions Drug: placebo
Drug: Omega-3 carboxylic acids
Drug: Dapagliflozin
Drug: Placebo
Enrollment 223
Recruitment Details This study was conducted in 5 centers in Sweden between 20 January 2015 and 11 December 2015.
Pre-assignment Details 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.
Arm/Group Title Epanova + Dapagliflozin Dapagliflozin Epanova Placebo
Hide Arm/Group Description Epanova 4 g/day + Dapagliflozin 10 mg/day Dapagliflozin 10 mg/day + placebo to Epanova Epanova 4 g/day + placebo to Dapagliflozin Placebo to Epanova and placebo to Dapagliflozin
Period Title: Overall Study
Started 22 21 20 21
Completed 20 20 15 20
Not Completed 2 1 5 1
Reason Not Completed
Couldn't swallow IP; noncompliance             0             0             2             0
Withdrawal by Subject             1             0             1             1
Adverse Event             1             1             2             0
Arm/Group Title Epanova + Dapagliflozin Epanova Dapagliflozin Placebo Total
Hide Arm/Group Description Epanova 4 g/day + Dapagliflozin 10 mg/day Epanova 4 g/day + placebo to Dapagliflozin Dapagliflozin 10 mg/day + placebo to Epanova Placebo to Epanova and placebo to Dapagliflozin Total of all reporting groups
Overall Number of Baseline Participants 22 20 21 21 84
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 21 participants 21 participants 84 participants
65.0  (5.42) 66.2  (5.94) 65.0  (6.54) 65.6  (6.10) 65.5  (5.92)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 21 participants 84 participants
<50 0 0 1 0 1
>=50 - <65 9 6 6 6 27
>=65 13 14 14 15 56
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 21 participants 84 participants
Female
7
  31.8%
9
  45.0%
5
  23.8%
4
  19.0%
25
  29.8%
Male
15
  68.2%
11
  55.0%
16
  76.2%
17
  81.0%
59
  70.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 21 participants 84 participants
Black Or African American 1 0 1 0 2
White 21 20 20 21 82
1.Primary Outcome
Title Change From Baseline to Week 12 in % Liver Fat as Assessed by MRI (Comparison Versus Placebo)
Hide Description 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.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Epanova + Dapagliflozin Placebo
Hide Arm/Group Description:
Epanova 4 g/day + Dapagliflozin 10 mg/day
Placebo to Epanova and placebo to Dapagliflozin
Overall Number of Participants Analyzed 20 19
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio of % liver fat
0.79
(0.69 to 0.90)
0.97
(0.90 to 1.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Epanova + Dapagliflozin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments Hypotheses tested using Dunnett’s multiple testing procedure with a family-wise error rate of 5%, adjusting for 3 pairwise comparisons versus a single control (placebo).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio for difference
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.70 to 1.00
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 12 in % Liver Fat (Comparison Between Active Treatment Groups)
Hide Description 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.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Epanova + Dapagliflozin Dapagliflozin Epanova
Hide Arm/Group Description:
Epanova 4 g/day + Dapagliflozin 10 mg/day
Dapagliflozin 10 mg/day + placebo to Epanova
Epanova 4 g/day + placebo to Dapagliflozin
Overall Number of Participants Analyzed 20 19 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio of % liver fat
0.79
(0.69 to 0.90)
0.87
(0.77 to 0.99)
0.85
(0.78 to 0.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Epanova + Dapagliflozin, Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.502
Comments Conditional upon rejection of at least 1 of the 3 hypotheses for the primary analysis, secondary hypotheses are tested using Tukey's multiple testing procedure with a family-wise error rate of 5%, adjusting for 3 pairwise comparisons.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio for difference
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.75 to 1.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Epanova + Dapagliflozin, Epanova
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.562
Comments Conditional upon rejection of at least 1 of the hypotheses for the primary analysis, secondary hypotheses are tested using Tukey's multiple testing procedure with a family-wise error rate of 5%, adjusting for 3 pairwise comparisons.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio for difference
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.73 to 1.13
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Epanova + Dapagliflozin Epanova Dapagliflozin Placebo
Hide Arm/Group Description Epanova 4 g/day + Dapagliflozin 10 mg/day Epanova 4 g/day + placebo to Dapagliflozin Dapagliflozin 10 mg/day + placebo to Epanova Placebo to Epanova and placebo to Dapagliflozin
All-Cause Mortality
Epanova + Dapagliflozin Epanova Dapagliflozin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Epanova + Dapagliflozin Epanova Dapagliflozin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/22 (0.00%)      0/20 (0.00%)      1/21 (4.76%)      1/21 (4.76%)    
Infections and infestations         
Sepsis  1  0/22 (0.00%)  0 0/20 (0.00%)  0 0/21 (0.00%)  0 1/21 (4.76%)  1
Renal and urinary disorders         
Hydronephrosis  1  0/22 (0.00%)  0 0/20 (0.00%)  0 1/21 (4.76%)  1 0/21 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Epanova + Dapagliflozin Epanova Dapagliflozin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/22 (63.64%)      12/20 (60.00%)      8/21 (38.10%)      7/21 (33.33%)    
Gastrointestinal disorders         
Abdominal pain upper  1  3/22 (13.64%)  3 2/20 (10.00%)  2 0/21 (0.00%)  0 0/21 (0.00%)  0
Constipation  1  0/22 (0.00%)  0 1/20 (5.00%)  1 2/21 (9.52%)  2 1/21 (4.76%)  1
Diarrhoea  1  11/22 (50.00%)  12 7/20 (35.00%)  7 1/21 (4.76%)  1 0/21 (0.00%)  0
Nausea  1  2/22 (9.09%)  2 3/20 (15.00%)  3 0/21 (0.00%)  0 2/21 (9.52%)  2
Infections and infestations         
Nasopharyngitis  1  2/22 (9.09%)  2 2/20 (10.00%)  2 1/21 (4.76%)  1 1/21 (4.76%)  2
Nervous system disorders         
Dizziness  1  2/22 (9.09%)  2 1/20 (5.00%)  1 5/21 (23.81%)  5 1/21 (4.76%)  1
Headache  1  1/22 (4.55%)  1 0/20 (0.00%)  0 0/21 (0.00%)  0 2/21 (9.52%)  2
Renal and urinary disorders         
Pollakiuria  1  2/22 (9.09%)  2 1/20 (5.00%)  1 2/21 (9.52%)  2 1/21 (4.76%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Stefan Carlsson
Organization: AstraZeneca
EMail: Stefan.C.Carlsson@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02279407    
Other Study ID Numbers: D5883C00004
First Submitted: October 29, 2014
First Posted: October 31, 2014
Results First Submitted: December 2, 2016
Results First Posted: January 27, 2017
Last Update Posted: March 17, 2017