The Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis

NCT ID: NCT04134091

Last Updated: 2023-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-27
• Study Completion Date: 2021-06-24

Brief 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.

Detailed Description

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. The study will be conducted across multiple centers in the United States.

Approximately 75 subjects will be randomized in 1:1:1 ratio to receive one of the following treatments:

• Treatment A: Oral LPCN 1144 Formulation A
• Treatment B: Oral LPCN 1144 Formulation B
• Treatment C: Oral matching placebo

Subjects will undergo a screening period to determine study eligibility. As a part of screening, liver biopsies will be performed for subjects who have not had a liver biopsy within 6 months of Day 1, and fat fraction will be measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) in all subjects. Adult male subjects with histologic evidence of NASH will be enrolled into the study.

Eligible subjects will be randomized to one of the three treatment arms. The treatment phase will be for a duration of 36-weeks with assessments of liver biopsies, hepatic fat fraction, liver enzymes, lipid levels and other safety parameters. Safety and tolerability will be assessed throughout the study.

Conditions

Nonalcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment A

LPCN 1144 Formulation A

Group Type: EXPERIMENTAL

LPCN 1144 Formulation A

Intervention Type: DRUG

Oral LPCN 1144 Formulation A capsule, total daily dose of 450 mg testosterone undecanoate administered as 225 mg testosterone undecanoate twice daily (BID).

Treatment B

LPCN 1144 Formulation B

Group Type: EXPERIMENTAL

LPCN 1144 Formulation B

Intervention Type: DRUG

Oral LPCN 1144 + d-alpha tocopherol total daily dose of 450 mg testosterone undecanoate + 476 mg d-alpha tocopherol administered as 225 mg testosterone undecanoate + 238 mg d-alpha tocopherol BID

Treatment C

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral matching placebo capsule administered as BID

Interventions

LPCN 1144 Formulation A

Oral LPCN 1144 Formulation A capsule, total daily dose of 450 mg testosterone undecanoate administered as 225 mg testosterone undecanoate twice daily (BID).

Intervention Type: DRUG

LPCN 1144 Formulation B

Oral LPCN 1144 + d-alpha tocopherol total daily dose of 450 mg testosterone undecanoate + 476 mg d-alpha tocopherol administered as 225 mg testosterone undecanoate + 238 mg d-alpha tocopherol BID

Intervention Type: DRUG

Placebo

Oral matching placebo capsule administered as BID

Intervention Type: DRUG

Other Intervention Names

testosterone undecanoate; testosterone undecanoate with d-alpha tocopherol; Oral placebo

Eligibility Criteria

Inclusion Criteria

1. Male between 18 and 80 years of age, inclusive.

2. Subject with histologic evidence of NASH upon central read of a liver biopsy.

i. A historical biopsy no more than 4 months before Screening may be considered for use with medical monitor approval if the following criteria are met:

• Stable weights between the time of the biopsy and Screening. Stable weight is defined as no more than a 5% change.
• Is either not taking or is on a stable dose of Thiazolidinedione(TZDs)/glitazones 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. Judged to be in good general health as determined by the investigator 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 > upper limits of normal (ULN)
• Hemoglobin > ULN
• Prostate-specific antigen (PSA) > 4 ng/mL
• Serum aspartate aminotransferase (AST) or alanine transaminase (ALT) > 200 IU/L
• Serum alkaline phosphatase (ALP) > 2 x ULN
• Serum creatinine of 2.0 mg/dL or greater
• Total 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

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. Any over-the-counter medication or herbal remedy that is being taken with an intent to improve hyperlipidemia must be stable for at least 3 months prior to randomization and through the end of the study.

14. 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.

15. Inability to safely obtain a liver biopsy.

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

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

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

19. History of biliary diversion.

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

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

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

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

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

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

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. Childhood seizures are not exclusionary.

28. 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.

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. 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 PI and/or Sponsor approval.

31. 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.

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

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

34. Failure to give informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Lipocine Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony DelConte

Role: STUDY_DIRECTOR

Lipocine Inc.

Locations

TriWest Research Associates, LLC

El Cajon, California, United States

United Medical Doctors

Murrieta, California, United States

Inland Empire Liver Foundation

Rialto, California, United States

Clinical Trials Research

Roseville, California, United States

Meridien Research-Maitland

Maitland, Florida, United States

Clinical Pharmacology of Miami, LLC

Miami, Florida, United States

Sensible Healthcare, LLC

Ocoee, Florida, United States

Tandem Clinical Research

Marrero, Louisiana, United States

Jubilee Clinical Research, Inc.

Las Vegas, Nevada, United States

Clinical Research of South Nevada

Las Vegas, Nevada, United States

Awasty Research Network

Marion, Ohio, United States

R&H Clinical Research

Katy, Texas, United States

Sun Research Institute

San Antonio, Texas, United States

Endeavor Clinical Trials

San Antonio, Texas, United States

Clinical Trial Network-Houston

Spring, Texas, United States

Pioneer Research Soultions

Sugar Land, Texas, United States

Advanced Clinical Research - Gut Whisperer

Riverton, Utah, United States

Granger Medical Clinic

West Valley City, Utah, United States

Manassas Clinical Research Center

Manassas, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LPCN 1144-18-002

Identifier Type: -

Identifier Source: org_study_id