A Study to Assess the Efficacy, Safety, and Tolerability of Oral LPCN 1148 in Male Subjects With Cirrhosis of the Liver and Sarcopenia

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is a randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of LPCN 1148 in men with cirrhosis of the liver and sarcopenia.

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

Details

• Lead Sponsor: Lipocine Inc.

Criteria

Inclusion Criteria:

1. Male ≥ 18 years old

2. Currently listed, on the liver transplant waitlist for cirrhosis secondary to Hepatitis B or C infection, Alcoholic Liver Disease (ALD), or Non-Alcoholic Steatohepatitis (NASH)

3. Evidence of sarcopenia with appropriate cutoff recommended by clinical guidance

Exclusion Criteria:

1. Suspected or proven hepatocellular carcinoma (HCC)

2. History of current or suspected prostate or breast cancer

3. History of malignancies other than prostate, breast, or HCC, unless successfully treated with curative intent and believed to be cured (defined as complete remission lasting at least 5 years)

4. History of uncontrolled or recurrent portal hypertensive bleeding, including uncontrolled or recurrent bleeding from varices, gastropathy, colopathy, or hemorrhoidal bleeding.

5. History or current thrombosis (including portal vein thrombosis), thromboembolism, or treatment for portal vein thrombosis

6. History of hemochromatosis

7. History of hypercoagulable state (e.g. Factor V Leiden deficiency, protein C deficiency, protein S deficiency, anti-thrombin III deficiency, or the presence of lupus anticoagulant)

8. Prior history of complications of ascites including:

1. Spontaneous bacterial peritonitis

2. Hepatic hydrothorax

9. MELD score > 25

10. Abnormal lab value in serum chemistry, hematology, or urinalysis that the PI considers clinically significant, including but not limited to:

1. PSA > 4 ng/mL

2. Polycythemia (Hematocrit >54%) or history of polycythemia

3. ALT or AST > 5x ULN

4. ALP > 1.5x ULN

5. Platelet count < 30,000/mL

6. EGFR < 60 mL/min/1.73 m2

7. Total bilirubin > 3.0 mg/dL

8. Serum albumin < 2.8 g/dL

9. INR > 2.3 or PT prolongation > 6.0 seconds

11. Subjects with PSA between 2.5 ng/mL and 4 ng/mL are excluded only if any of the below criteria are met at baseline:

1. Hematocrit > 48%

2. I-PSS > 19

3. Any irregularity found on digital rectal examination of the prostate

12. Subjects with PSA > 3 ng/mL are excluded only if any of the below criteria are met at baseline:

1. Subject is African American

2. Subject has a first-degree relative who has a history of prostate cancer

3. Hematocrit > 48%

4. I-PSS > 19

5. Any irregularity found on digital rectal examination of the prostate

13. Clinically significant abnormal prostate digital rectal examination (DRE) in the opinion of the PI, with DRE screening initiated at International Prostate Symptom Score (I-PSS) > 19

14. History of bariatric surgery

15. History of stroke or myocardial infarction within the past 5 years

16. Known positivity for Human Immunodeficiency Virus (HIV) infection

17. Acute liver failure as the indication for addition to the liver transplant waitlist

18. Estimated life expectancy less than 3 months or expected to undergo liver transplant within 3 months

19. Known heart failure of New York Heart Association class III or IV

20. Evidence of severe encephalopathy or encephalopathy that is not controlled despite adequate medical therapy

21. History of prior organ transplant

22. History of Fontan physiology

23. History of pulmonary embolus

24. Porto-pulmonary hypertension

25. Hepatopulmonary syndrome

26. Uncontrolled epilepsy or migraine

27. Active substance abuse or dependency extending to within the previous 6 months

28. History of significant sensitivity or allergy to testosterone, or product excipients.

29. Use of known strong 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

30. Subjects who are currently receiving any androgens (testosterone or other androgens or androgen-containing supplements) and are unwilling to washout prior to screening

a. Washout: 12 weeks following long-acting intramuscular androgen injections; 4 weeks following topical or buccal androgens; 3 weeks following oral androgens

31. Uncontrolled hypertension (>160/90 mmHg despite treatment)

32. Uncontrolled obstructive sleep apnea

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

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 to the study protocol (including diet, exercise, and alcohol abstinence) or hinder completion of the study

36. Failure to give informed consent