A Study to Assess the Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis (NASH)

• Status: Active, not recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is a Phase 2, randomized, double-blind, placebo controlled, three arm study in adult men with biopsy confirmed NASH. The study is aimed at evaluating efficacy and tolerability of LPCN 1144 in adult men with NASH.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lipocine Inc.

Criteria

Inclusion Criteria:

1. Adult male subject with histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by NASH activity score (NAS) greater than or equal to 4 with at least 1 point each in inflammation and ballooning. Subjects who have had a biopsy more than 3 months before trial enrollment should have stable weights between the time of the biopsy and trial initiation. Stable weight is defined as no more than a 5% change.

2. For subjects with a historical biopsy, is either not taking or is on stable doses of TZDs/glitazones or vitamin E (d-alpha tocopherol) for 3 months before Day 1.

3. Background therapy for other ongoing chronic conditions, and weight should be stable for at least 3 months before trial enrollment. Stable weight is defined as no more than a 5% change.

4. A previous historical diagnosis of hypogonadism or low testosterone at screening.

Exclusion Criteria:

1. Significant alcohol consumption more than 30 g/day on average, either currently or for a period of more than 3 consecutive months in the 5 years prior to screening.

2. Inability to reliably quantify alcohol intake.

3. Biochemical, clinical or histologic evidence of cirrhosis on liver biopsy (stage 4 fibrosis).

4. Evidence of other causes of chronic liver disease including alcoholic liver disease, viral hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, human immunodeficiency virus, etc.

5. Suspected or proven liver cancer

6. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to:

• Hematocrit > ULN

• Hemoglobin > ULN

• PSA > 4 ng/mL

• Serum AST or ALT > 200 IU/L

• Serum ALP > 2 x ULN

• Serum creatinine of 2.0 mg/dL or greater

• Bilirubin > ULN

• International normalized ratio (INR) ≥ 1.3.

• Prolactin > ULN

7. Subjects with evidence of worsening liver function based on the two initial laboratory values used to establish the screening / baseline values.

8. Model for End-Stage Liver Disease (MELD) score greater than 12

9. Subjects with a documented history of Gilbert's syndrome with bilirubin outside the normal reference range.

10. Evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly).

11. Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens, anabolic steroids, valproic acid, other known hepatotoxins) for more than 2 weeks in the 2 years prior to randomization.

12. Subjects who are not on a stable dose of lipid-lowering drugs, diabetic and / or hypertensive medication in the 3 months prior to biopsy or the 3 months prior to randomization

13. Inability to safely obtain a liver biopsy.

14. History of total parenteral nutrition in the year prior to screening.

15. History of bariatric surgery or currently undergoing evaluation for bariatric surgery.

16. History of gastric surgery, cholecystectomy, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.

17. History of biliary diversion.

18. Known positivity for antibody to Human Immunodeficiency Virus (HIV).

19. Known heart failure of New York Heart Association class 3 or 4.

20. Active, serious medical disease with likely life-expectancy less than 5 years.

21. History of current or suspected prostate or breast cancer.

22. History of diagnosed, severe, untreated, obstructive sleep apnea.

23. Active substance abuse in the year prior to screening.

24. History of significant sensitivity or allergy to any androgens, including testosterone, or product excipients

25. Participation in an investigational new drug trial in the 30 days prior to randomization without the approval of the PI and/or Sponsor.

26. History of significant sensitivity or allergy to any androgens, including testosterone, or product excipients.

27. History of seizures or convulsions, including alcohol or drug withdrawal seizures.

28. Use of known inhibitors (e.g., ketoconazole) or inducers (e.g., dexamethasone, phenytoin, rifampin, carbamazepine) of cytochrome P450 3A (CYP3A) within 30 days prior to study drug administration and through the end of the study.

29. Subjects who are currently receiving any androgens (testosterone or other androgens or androgen supplements). Subjects who are on testosterone may be eligible for the study following an adequate washout (12 weeks following intramuscular androgen injections; 4 weeks following topical or buccal androgens; 3 weeks following oral androgens).

30. Vitamin E supplementation of greater than 100 IU/day, unless completed adequate washout for at least 4 weeks prior to Day 1 or biopsy if one is required.

31. Use of any drug within 5 half-lives of the last dose in the past 6 months prior to Study Day -2 without PI and/or Sponsor approval.

32. Any contraindications to a MRI scan (i.e. subjects with non-removable ferromagnetic implants, pacemakers, aneurysm clips or other foreign bodies), and/or subjects with claustrophobic symptoms and/or inability to fit into an MRI scanner.

33. Receipt of any drug by injection within 30 days or 10 half-lives (whichever is longer) prior to study drug administration without PI and/or Sponsor approval. Insulin, allergy shots, and vaccines are allowed.

34. Subject who is not willing to use adequate contraception for the duration of the study.

35. Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study.

36. Failure to give informed consent.