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

Phase 2

Completed

• Conditions: Sarcopenia; Liver Cirrhosis
• Interventions: Drug: Placebo; Drug: LPCN 1148

• Registration Number: NCT04874350
• Lead Sponsor: Lipocine Inc.

Brief 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.

Detailed Description

This is a 52-week, multicenter, double-blind, placebo-controlled, two arm study of LPCN 1148 in adult men with cirrhosis of the liver and sarcopenia on the liver transplant waitlist. This study will evaluate the efficacy, safety, and tolerability of LPCN 1148, determined through a range of clinical outcomes and functional and laboratory tests.

Approximately 48 subjects will be randomized 1:1 ratio to receive one of the following treatments:

* Treatment A: Oral LPCN 1148

* Treatment B: Oral matching placebo.

Subjects will undergo a screening period to determine study eligibility. Adult male subjects with liver cirrhosis and sarcopenia on the transplant list will be enrolled into the study.

There are two treatment phases to this study.

* Stage 1: 24 weeks of blinded study treatment (LPCN 1148 or matching placebo)

* Stage 2: 28-week open-label extension. Subjects who participate in Stage 1 of this trial will roll over to a 28-week open-label extension phase. All subjects will receive LPCN 1148; there will be no placebo in the extension period.

Study Timeline

• Study First Submitted: 2021-05-03
• Study First Submitted QC: 2021-05-03
• Study First Posted: 2021-05-05
• Study Start: 2021-11-30
• Primary Completion: 2023-12-18
• Study Completion: 2023-12-18
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-12
• Last Update Posted: 2024-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

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), Non-Alcoholic Steatohepatitis (NASH), Primary Biliary Cholangitis (PBC), or Primary Sclerosing Cholangitis (PSC)
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 in the past 6 months.

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 in the past 6 months 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 > ULN) or history of polycythemia
    3. ALT or AST > 5x ULN
    4. ALP > 2x ULN; subjects with PBC or PSC are excluded if ALP is > 10x ULN
    5. Platelet count < 30,000/mL
    6. EGFR < 30 mL/min/1.73 m2 for subjects not undergoing routine, scheduled dialysis
    7. Serum albumin < 2.0 g/dL
    8. INR > 2.3

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. History of TIPS within the past 6 months, or TIPS procedure expected within 6 months of Day 1

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

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

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

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

21. Evidence of severe encephalopathy at screening encephalopathy that is not controlled despite adequate medical therapy

22. History of prior organ transplant

23. History of Fontan physiology

24. History of pulmonary embolus

25. Porto-pulmonary hypertension

26. Hepatopulmonary syndrome requiring standing home supplemental oxygen therapy, or MELD exception points for hepatopulmonary syndrome

27. Uncontrolled epilepsy or migraine

28. Active substance abuse or dependency extending to within the previous 3 months

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

30. 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

31. 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

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

33. Uncontrolled obstructive sleep apnea

34. 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

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

36. 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

37. Failure to give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Oral matching placebo capsules, administered as BID.
LPCN 1148	LPCN 1148	Oral LPCN 1148 capsules, administered as BID.

Primary Outcome Measures

Name	Time	Method
Change from baseline in Skeletal Muscle Index in LPCN 1148 treated subjects compared to placebo	24 weeks

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Liver Frailty Index in LPCN 1148 treated subjects compared to placebo	24 weeks
Change in number of breakthrough hepatic encephalopathy events in LPCN 1148 treated subjects compared to placebo	24 weeks	Breakthrough hepatic encephalopathy was defined as events of hepatic encephalopathy with a Common Terminology Criteria for Adverse Events grade greater than grade 1

Trial Locations

Locations (10)

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Methodist Health System; 🇺🇸 Dallas, Texas, United States

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Intermountain Healthcare; 🇺🇸 Murray, Utah, United States

Mt.Olympus Medical Research; 🇺🇸 Houston, Texas, United States