Hypertriglyceridemia, Type 2 Diabetes
Conditions
Brief summary
To assess the efficacy and safety of orally administered Epeleuton capsules versus placebo, in the treatment of adult patients with hypertriglyceridemia and type 2 diabetes
Detailed description
This was a randomised, double-blind, Placebo-controlled, 3-arm, multi-centre Phase IIb study consisting of 26 weeks of active treatment and a 2-week post-treatment follow-up period in adult patients with hypertriglyceridemia and concomitant type 2 diabetes. The screening period consisted of up to 6-weeks lead-in during which all patients were to undergo diet and lifestyle stabilisation, washout of disallowed medications and optimisation of statins. After screening, patients were randomised (1:1:1) at the baseline visit into the following treatment groups: * Treatment Group A (Placebo): four Placebo capsules orally administered twice a day, i.e., eight capsules daily for 26 weeks. * Treatment Group B (Epeleuton 2g): two Epeleuton 500 mg capsules and two Placebo capsules orally administered twice a day, i.e., eight capsules daily for 26 weeks. * Treatment Group C (Epeleuton 4g): four Epeleuton 500 mg capsules orally administered twice a day, i.e., eight capsules daily for 26 weeks. The observation period was 32-34 weeks (lead-in: 4-6 weeks, treatment duration: 26 weeks, follow-up period: 2 weeks). During the study, 10 visits to the clinic were scheduled: two screening visits (Visit 1 and Visit 2), one visit at the start of the comparative treatment period (baseline/Visit 3), six visits in the comparative treatment period (Visit 4/Week 4, Visit 5/Week 8, Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 20 and Visit 9/Week 26 or Early Termination) and one final safety follow-up visit (Visit 10/Week 28).
Interventions
DRUGDS102
DS102 Epeleuton capsules
DRUGPlacebo
Placebo capsules
Sponsors
Afimmune
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients diagnosed with type 2 diabetes mellitus at least 90 days prior to the first screening visit. 2. Patients with a HbA1C (glycosylated haemoglobin) between 7.0 - 10.0% (53-86 mmol/mol) (both inclusive) 3. Patients with a fasting triglyceride level ≥200 mg/dL (2.26 mmol/L) and \<750mg/dL (8.46 mmol/L) at both screening visits. Note: If the triglyceride level is outside the required range at the second screening visit, an additional measurement can be obtained 1 week later, to confirm eligibility. Note: If a large difference in triglyceride level (\>15%) is observed between screening 1 and screening 2, an additional measurement may be requested or patient may be deemed not eligible. 4. Patients who have been educated regarding diet and exercise at or before visit 1 (screening 1) and are willing to maintain and not alter a stable diet and activity routine throughout the study. 5. Patients who have been on a stable statin therapy at doses that are likely to achieve optimal LDL cholesterol and who are willing to continue this treatment throughout the study. Note: Stable statin therapy may consist of a statin with or without ezetimibe. 6. Patients with an LDL cholesterol level \<130mg/dL (3.34 mmol/L) at both screening visits. 7. Patients who have a body mass index (BMI) ≥ 25kg/m2 and \<50kg/m2. 8. Patients who have been on a stable daily dose of metformin (at least 1500mg or maximum tolerated dose for metformin monotherapy as documented in the subject medical record) and/or a sulfonylurea and/or a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or a sodium-glucose transport protein 2 inhibitor (SGLT2i) and/or a GLP1-RA and/or basal insulin for at least 90 days prior to the day of first screening visit. Note: Dose of GLP1-RA must be stable for 6 months prior to baseline with no weight change \>2kg for 3 months prior to baseline. Note: Dose of basal insulin must be stable for 4 months prior to baseline. All types of basal insulin are permitted, including insulin glargine, insulin degludec, insulin detemir, NPH insulin and pre-mixed insulin. 9. Female patients and male patients with female partners of childbearing potential must use highly effective contraceptive methods or have a sterilised partner for the duration of the study. Highly effective contraceptive methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include hormonal contraception, intrauterine device or sexual abstinence. Note: A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Note: Hormonal contraceptives must be on a stable dose for at least one month before baseline. Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. 10. Patients whose pre-study or screening clinical laboratory findings do not interfere with their participation in the study, in the opinion of the Investigator, and do not violate any inclusion or
Exclusion criteria
11. Male or female patients aged 18 years and older on the day of signing the informed consent form (ICF). 12. Patients who are able to communicate well with the Investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent prior to initiation of any study specific activities or procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Triglycerides From Baseline to Week 16 | 16 weeks | Analysis of changes and percentage changes of triglycerides was performed using a Wilcoxon rank sum test with the Hodges Lehmann median and 95% confidence intervals estimates. For analysis of triglycerides, baseline was defined as the mean of the Baseline (Visit 3) and Screening 2/Week -1 (Visit 2) measurements. |
| Change in HbA1c From Baseline to Week 26 | 26 weeks | Changes from baseline of HbA1c at each visit were analysed using mixed model analysis of covariance (ANCOVA) with baseline value as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | 26 weeks | Percent change in triglycerides from baseline to weeks 4, 8, 12, 20 and 26 |
| Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | 20 weeks | Change in HbA1c (glycosylated haemoglobin) from baseline to weeks 4, 8, 12, 16 and 20 |
Countries
Georgia, Germany, Israel, Latvia, Switzerland, United States
Participant flow
Pre-assignment details
A total of 233 patients were randomized in a 1:1:1 ratio
Participants by arm
| Arm | Count |
|---|---|
| DS102 2000mg Participants in this group received 1000mg DS102 capsules twice daily.
DS102: DS102 Epeleuton capsules | 79 |
| DS102 4000mg Participants in this group received 2000mg DS102 capsules twice daily.
DS102: DS102 Epeleuton capsules | 77 |
| Placebo Participants in this group received placebo capsules twice daily.
Placebo: Placebo capsules | 77 |
| Total | 233 |
Baseline characteristics
| Characteristic | DS102 2000mg | DS102 4000mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 9.3 | 58.9 years STANDARD_DEVIATION 10.2 | 58.8 years STANDARD_DEVIATION 10.1 | 59.7 years STANDARD_DEVIATION 9.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 75 Participants | 74 Participants | 70 Participants | 219 Participants |
| Sex: Female, Male Female | 34 Participants | 30 Participants | 28 Participants | 92 Participants |
| Sex: Female, Male Male | 45 Participants | 47 Participants | 49 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 77 | 0 / 77 |
| other Total, other adverse events | 49 / 79 | 52 / 77 | 42 / 77 |
| serious Total, serious adverse events | 1 / 79 | 0 / 77 | 1 / 77 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 26
Changes from baseline of HbA1c at each visit were analysed using mixed model analysis of covariance (ANCOVA) with baseline value as a covariate.
Time frame: 26 weeks
Population: Full Analysis Set (FAS):~Patients were included in the FAS, a modified intention-to-treat population, if they were randomised to the study, received at least one dose of study medication and had at least one post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS102 2000mg | Change in HbA1c From Baseline to Week 26 | -2.255 % of HbA1c | Standard Error 1.412 |
| DS102 4000mg | Change in HbA1c From Baseline to Week 26 | -0.524 % of HbA1c | Standard Error 1.162 |
| Placebo | Change in HbA1c From Baseline to Week 26 | -0.503 % of HbA1c | Standard Error 1.446 |
p-value: 0.865895% CI: [-0.26658, 0.316897]ANCOVA
p-value: 0.6595% CI: [-0.39012, 0.243455]ANCOVA
Primary
Percent Change in Triglycerides From Baseline to Week 16
Analysis of changes and percentage changes of triglycerides was performed using a Wilcoxon rank sum test with the Hodges Lehmann median and 95% confidence intervals estimates. For analysis of triglycerides, baseline was defined as the mean of the Baseline (Visit 3) and Screening 2/Week -1 (Visit 2) measurements.
Time frame: 16 weeks
Population: Full Analysis Set (FAS):~Patients were included in the FAS, a modified intention-to-treat population, if they were randomised to the study, received at least one dose of study medication and had at least one post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS102 2000mg | Percent Change in Triglycerides From Baseline to Week 16 | -7.886 % Change in TG | Standard Error 4.096 |
| DS102 4000mg | Percent Change in Triglycerides From Baseline to Week 16 | 5.273 % Change in TG | Standard Error 5.361 |
| Placebo | Percent Change in Triglycerides From Baseline to Week 16 | -5.130 % Change in TG | Standard Error 4.945 |
p-value: 0.114812495% CI: [-2.01, 18.19]Wilcoxon (Mann-Whitney)
p-value: 0.866846795% CI: [-10.16, 7.96]Wilcoxon (Mann-Whitney)
Secondary
Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20
Change in HbA1c (glycosylated haemoglobin) from baseline to weeks 4, 8, 12, 16 and 20
Time frame: 20 weeks
Population: Full Analysis Set (FAS):~Patients were included in the FAS, a modified intention-to-treat population, if they were randomised to the study, received at least one dose of study medication and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS102 2000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 16 - Baseline | -2.690 % HbA1c | Standard Error 1.338 |
| DS102 2000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 12 - Baseline | -3.448 % HbA1c | Standard Error 1.229 |
| DS102 2000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 4 - Baseline | -2.606 % HbA1c | Standard Error 0.618 |
| DS102 2000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 8 - Baseline | -3.327 % HbA1c | Standard Error 0.978 |
| DS102 2000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 20 - Baseline | -4.176 % HbA1c | Standard Error 1.414 |
| DS102 4000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 12 - Baseline | -2.331 % HbA1c | Standard Error 1.052 |
| DS102 4000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 4 - Baseline | -1.980 % HbA1c | Standard Error 0.683 |
| DS102 4000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 8 - Baseline | -2.933 % HbA1c | Standard Error 0.815 |
| DS102 4000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 16 - Baseline | -1.733 % HbA1c | Standard Error 1.11 |
| DS102 4000mg | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 20 - Baseline | -0.733 % HbA1c | Standard Error 1.188 |
| Placebo | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 20 - Baseline | -0.811 % HbA1c | Standard Error 1.372 |
| Placebo | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 16 - Baseline | -1.278 % HbA1c | Standard Error 1.216 |
| Placebo | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 4 - Baseline | -1.365 % HbA1c | Standard Error 0.657 |
| Placebo | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 12 - Baseline | -1.315 % HbA1c | Standard Error 1.143 |
| Placebo | Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20 | Week 8 - Baseline | -2.913 % HbA1c | Standard Error 0.861 |
Secondary
% Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26
Percent change in triglycerides from baseline to weeks 4, 8, 12, 20 and 26
Time frame: 26 weeks
Population: Full Analysis Set (FAS):~Patients were included in the FAS, a modified intention-to-treat population, if they were randomised to the study, received at least one dose of study medication and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS102 2000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 20 - Baseline | -5.666 % Change in TG | Standard Error 4.665 |
| DS102 2000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 12 - Baseline | -8.144 % Change in TG | Standard Error 4.071 |
| DS102 2000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 4 - Baseline | -9.301 % Change in TG | Standard Error 3.994 |
| DS102 2000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 8 - Baseline | -5.018 % Change in TG | Standard Error 3.843 |
| DS102 2000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week26 - Baseline | -8.213 % Change in TG | Standard Error 4.882 |
| DS102 4000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 12 - Baseline | -4.215 % Change in TG | Standard Error 6.081 |
| DS102 4000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 4 - Baseline | 5.965 % Change in TG | Standard Error 9.868 |
| DS102 4000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 8 - Baseline | -4.500 % Change in TG | Standard Error 4.623 |
| DS102 4000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 20 - Baseline | 1.889 % Change in TG | Standard Error 5.005 |
| DS102 4000mg | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week26 - Baseline | 7.456 % Change in TG | Standard Error 6.585 |
| Placebo | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week26 - Baseline | -0.675 % Change in TG | Standard Error 5.538 |
| Placebo | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 20 - Baseline | -4.270 % Change in TG | Standard Error 4.494 |
| Placebo | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 4 - Baseline | -6.025 % Change in TG | Standard Error 4.479 |
| Placebo | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 12 - Baseline | 4.022 % Change in TG | Standard Error 5.532 |
| Placebo | % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26 | Week 8 - Baseline | -5.242 % Change in TG | Standard Error 4.411 |