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

• Sponsor: Lipocine Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04874350
• Collaborator: (none)
• Enrollment: 60
• Locations: 10
• Arms: 2
• Anticipated Duration (Months): 23.4
• Patients Per Site: 6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis; Sarcopenia	Drug: LPCN 1148; Drug: Placebo	Phase 2

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 60 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized 1:1 to LPCN 1148 or placeboRandomized 1:1 to LPCN 1148 or placebo
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of Oral LPCN 1148 in Male Subjects With Cirrhosis of the Liver and Sarcopenia
• Actual Study Start Date: Dec 20, 2021
• Anticipated Primary Completion Date: Sep 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LPCN 1148 Oral LPCN 1148 capsules, administered as BID.	Drug: LPCN 1148; LPCN 1148 is an oral capsule product containing an ester prodrug of bioidentical testosterone, designed to enable absorption via intestinal lymphatics.
Placebo Comparator: Placebo Oral matching placebo capsules, administered as BID.	Drug: Placebo; Oral matching placebo capsule

Outcome Measures

Primary Outcome Measures

1. Change from baseline in Skeletal Muscle Index in LPCN 1148 treated subjects compared to placebo [24 weeks]

Secondary Outcome Measures

1. Change from baseline in Liver Frailty Index in LPCN 1148 treated subjects compared to placebo [Up to 52 weeks]

2. Change in number of waitlist events in LPCN 1148 treated subjects compared to placebo [Up to 52 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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:

9. Spontaneous bacterial peritonitis

10. Hepatic hydrothorax

11. MELD score > 25

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

13. PSA > 4 ng/mL

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

15. ALT or AST > 5x ULN

16. ALP > 1.5x ULN

17. Platelet count < 30,000/mL

18. EGFR < 60 mL/min/1.73 m2

19. Total bilirubin > 3.0 mg/dL

20. Serum albumin < 2.8 g/dL

21. INR > 2.3 or PT prolongation > 6.0 seconds

22. 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:

23. Hematocrit > 48%

24. I-PSS > 19

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

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

27. Subject is African American

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

29. Hematocrit > 48%

30. I-PSS > 19

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

32. 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

33. History of bariatric surgery

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

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

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

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

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

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

40. History of prior organ transplant

41. History of Fontan physiology

42. History of pulmonary embolus

43. Porto-pulmonary hypertension

44. Hepatopulmonary syndrome

45. Uncontrolled epilepsy or migraine

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

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

48. 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

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

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

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

2. Uncontrolled obstructive sleep apnea

3. 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

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

5. 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

6. Failure to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	University of California, Los Angeles	Los Angeles	California	United States	90095
3	University of California San Francisco	San Francisco	California	United States	94117
4	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
5	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
6	Methodist Health System	Dallas	Texas	United States	75203
7	University of Texas Southwestern	Dallas	Texas	United States	75309
8	Mt.Olympus Medical Research	Houston	Texas	United States	77030
9	Intermountain Healthcare	Murray	Utah	United States	84107
10	University of Utah	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• Lipocine Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lipocine Inc.
• ClinicalTrials.gov Identifier: NCT04874350
• Other Study ID Numbers: LPCN 1148-21-001
• First Posted: May 5, 2021
• Last Update Posted: Jun 23, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Liver Cirrhosis; Sarcopenia; Fibrosis

Study Results

No Results Posted as of Jun 23, 2022