Hypertriglyceridemia and Type 2 Diabetes MedDRA version: 20.1 Level: LLT Classification code 10020870 Term: Hypertriglyceridemia System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 21.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Afimmune Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 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 t
Exclusion criteria
Exclusion criteria: 1. Patients who have a history of intolerance or hypersensitivity to any substance in epeleuton capsules, placebo capsules or statins. 2. Patients with uncontrolled hypertension defined as a systolic blood pressure =160 mmHg or a diastolic blood pressure =100mmHg. 3. Patients who have a body mass index (BMI) 2kg from the first screening visit to the baseline visit. 5. Patients who have type 1 diabetes mellitus. 6. Patients who have thyroid stimulating hormone (TSH) levels >1.5 times the upper limit of normal. 7. Patients with known familial lipoprotein lipase deficiency (Fredriksen type I), apolipoprotein C-II deficiency or familial dysbetaliproteinemia (Fredriksen type III). 8. Patients with significant liver disease or liver function impairment defined as any of the following; cirrhosis, hepatitis, biliary obstruction with hyperbilirubinemia (total bilirubin >2 times the upper limit of normal) and aspartate aminotransferase (AST) or alanine aminotransferase levels (ALT) >3 times the upper limit of normal. 9. Patients with renal impairment defined as an estimated glomerular filtration rate 10 times the upper limit of normal or creatine kinase elevation due to known muscle disease at visit 1 (screening 1) 21. Patients who are classified as being in New York Heart Association (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy Objective: • To assess the efficacy of orally administered Epeleuton capsules versus placebo, in the treatment of adult patients with hypertriglyceridemia and type 2 diabetes. Safety Objective: • To assess the safety of orally administered Epeleuton capsules versus placebo, in the treatment of adult patients with hypertriglyceridemia and type 2 diabetes. ;Secondary Objective: Not applicable;Primary end point(s): • Percent change in triglycerides from baseline to week 16. • Change in HbA1c from baseline to week 26. Note: • Each of the independent primary endpoints will be analysed separately. • The primary endpoints will be analysed in a hierarchical testing sequence in the following order: 1. Percent change in triglycerides – Epeleuton 4g/day vs Placebo 2. Percent change in triglycerides – Epeleuton 2g/day vs Placebo 3. Change in HbA1c – Epeleuton 4g/day vs Placebo 4. Change in HbA1c – Epeleuton 2g/day vs Placebo ;Timepoint(s) of evaluation of this end point: Baseline, week 16 and week 26 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints • 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. • Proportion of patients achieving a HbA1c below 7.0% at weeks 4, 8, 12, 16, 20 and 26. • Percent change in very low-density lipoprotein cholesterol (VLDL-C) from baseline to weeks 4, 8, 12, 16, 20 and 26. • Percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to weeks 4, 8, 12, 16, 20 and 26. • Percent change in total cholesterol from baseline to weeks 4, 8, 12, 16, 20 and 26. • Change in fasting plasma glucose from baseline to weeks 4, 8, 12, 16, 20 and 26. • Proportion of patients achieving a HbA1c below 6.5% at weeks 4, 8, 12, 16, 20 and 26. • Percent change in apolipoprotein B (ApoB) from baseline to weeks 16 and 26. • Percent change in remnant lipoprotein cholesterol (RLP-C) from baseline to weeks 8, 16 and 26. • Percent change in high-density lipoprotein cholesterol (HDL-C) from baseline to weeks 4, 8, 12, 16, 20 and 26. • Percent change in low-density lipoprotein cholesterol (LDL-C) (preparative ultracentrifugation) from baseline to weeks 16 and 26. • Change in body weight (kg) from baseline to weeks 4, 8, 12, 16, 20 and 26. • Change in high-sensitivity C-reactive protein (hsCRP) from baseline to weeks 8, 16 and 26. • Change in systolic blood pressure from baseline to weeks 4, 8, 12, 16, 20 and 26. • Change in diastolic blood pressure from baseline to weeks 4, 8, 12, 16, 20 and 26. • Change in urinary albumin-to-creatinine ratio (UACR) from baseline to week 26 in the subgroup of patients with microalbuminuria at baseline. Exploratory Endpoints • Change in waist circumference from baseline to weeks 8, 16 and 26. • Percent change in apolipoprotein CIII (ApoCIII) from baseline to weeks 16 and 26. • Percent change in apolipoprotein A1 (ApoA1) from baseline to weeks 16 and 26. • Percent change in lipoprotein (a) (Lp(a)) from base | — |
Countries
Georgia, Germany, Israel, Latvia, Switzerland, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs Department
Afimmune Ltd.
Outcome results
None listed