NASH - Nonalcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Type2 Diabetes
Conditions
Keywords
Diabetes, NASH, NAFLD
Brief summary
This is a randomized, double-blind study of MSDC-0602K or placebo in subjects with pre-T2D or T2D and evidence of NAFLD/NASH.
Detailed description
This is a randomized, double-blind study of MSDC-0602K or placebo given orally once daily to subjects with pre-T2D or T2D and evidence of NAFLD/NASH. Visits will include a Screening Period, a minimum Treatment of 26 weeks, and a Long-Term Follow-up Period during which subjects will continue taking assigned treatment. Safety will be assessed by periodic measurement of vital signs, physical examinations, blood laboratory analyses, and the occurrence of adverse events.
Interventions
DRUGMSDC-0602K
MSDC-0602K tablet
DRUGPlacebo
Matching tablet
Sponsors
Cirius Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Written informed consent. 2. Adult subjects with an age of \> 18 years but \< 80 years. 3. Male or female subjects with reproductive potential must agree to comply with approved double barrier contraceptive method for the duration of the trial. Females of non-childbearing potential are considered: Post-menopausal Surgically sterile 4. Diagnosis of NAFLD 5. AST\>27 U/L 6. HgbA1c \>6% 7. Diagnosis of Pre-T2D or T2D 8. History of macrovascular cardiovascular disease Key
Exclusion criteria
1. Prior liver transplantation or currently on transplant list. 2. Other well-documented causes of active chronic liver disease 3. Current cirrhosis 4. Pregnant or nursing women 5. AST or ALT \> 5 times the upper limit of normal 6. Total bilirubin \> 1.3 mg/dL unless diagnosis of Gilbert's disease with direct bilirubin within normal reference range 7. Serum albumin \< 3.5 g/dL at Screening 8. Alkaline phosphatase \>2 times the upper limit of normal at Screening 9. Estimated glomerular filtration rate (eGFR by MDRD) \<30 ml/min/1.73 m2 but ≤75 ml/min/1.73 m2 10. In patients who are not anticoagulated, INR ≥ 1.3 times ULN at Screening or other evidence of impaired coagulation. 11. Acute vascular events including ACS, stroke or TIA, worsening of peripheral vascular disease or any vascular/cardiac procedure 12. Limb amputation for reason other than trauma. 13. HbA1c \>10% 14. Any planned surgery or device implantation after screening 15. Ejection fraction \< 35% or Heart failure with NYHA class IV 16. History of alcohol abuse or drug abuse within 6 months prior to Screening Diagnosis at any time of Type 1 diabetes. 17. Current or history of recent (≤ 6 months) use of ursodeoxycholic acid. 18. Current use of insulin. 19. Current use of thiazolidinediones. 20. Any history or current concomitant disorder such as haematological, pulmonary, metabolic, endocrine disorders that are severe or life-threatening. 21. Use of concomitant medications with a known significant metabolism by CYP2C8 including paclitaxel or repaglinide for the duration of the study. 22. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within the 6 months prior to Screening. 23. Known or suspected intolerance or hypersensitivity to the study drugs, closely related compounds such as PPARγ agonists (pioglitazone or rosiglitazone), or any of their stated ingredients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glycosylated hemoglobin (HbA1c) from baseline to Week 26 | 26 weeks | — |
| Change in the weighted average of standardized AST, CK-18, and HbA1c values (standard deviations) from baseline to Week 26 | 26 weeks | This is a single composite outcome measure. This is derived by standardizing the values of AST, CK-18, and HbA1c by subtracting the respective study population means and dividing by respective study population standard deviations at each time point; averaging these standardized AST, CK-18,and HbA1c values (or z-scores) for a given patient at each time point; and then computing the difference from baseline to week 26 with respect to these averages. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first event of death, adjudicated nonfatal MI or USA hospitalization, adjudicated hospital admission for HF, or adjudicated nonfatal ischemic stroke. | through study completion, an expected average of 15 months | — |
| Time to first event of death or adjudicated non-fatal MI or USA hospitalization, adjudicated hospital admission for HF, adjudicated nonfatal ischemic stroke, or liver event in all randomized subjects. | through study completion, an expected average of 15 months | A liver event consists of ascites (confirmed by paracentesis or abdominal imaging), hepatic encephalopathy (defined clinically), variceal hemorrhage (confirmed by endoscopy), or liver transplant. |
Outcome results
None listed