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Nonalcoholic Steatohepatitis (NASH)Phase 2NASHNCT04134091

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

A Phase 2 study testing LPCN 1144 Formulation A and LPCN 1144 Formulation B in people with Nonalcoholic Steatohepatitis (NASH), run by Lipocine Inc. at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years, men only
Conditions the study is for
Nonalcoholic Steatohepatitis (NASH)
What is being tested?
LPCN 1144 Formulation A and LPCN 1144 Formulation B
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
56 participants
Where
19 sitesUnited States
Study dates
27 Aug 2019to 24 Jun 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male between 18 and 80 years of age, inclusive.
  • Subject with histologic evidence of NASH upon central read of a liver biopsy.
  • 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.
  • 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.
  • Judged to be in good general health as determined by the investigator at screening.

Who cannot join

  • 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.
  • Inability to reliably quantify alcohol intake.
  • Biochemical, clinical or histologic evidence of cirrhosis on liver biopsy (stage 4 fibrosis).
  • 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.
  • Suspected or proven liver cancer.
  • Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to:
Show all 43Show fewer
  • 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
  • Subjects with evidence of worsening liver function based on the two initial laboratory values used to establish the screening / baseline values.
  • Model for End-Stage Liver Disease (MELD) score greater than 12
  • Subjects with a documented history of Gilbert's syndrome
  • Evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly).
  • 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.
  • 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
  • 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.
  • 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.
  • Inability to safely obtain a liver biopsy.
  • History of total parenteral nutrition in the year prior to screening.
  • History of bariatric surgery or currently undergoing evaluation for bariatric surgery.
  • History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.
  • History of biliary diversion.
  • Known positivity for antibody to Human Immunodeficiency Virus (HIV).
  • Known heart failure of New York Heart Association class 3 or 4.
  • Active, serious medical disease with likely life-expectancy less than 5 years.
  • History of current or suspected prostate or breast cancer.
  • History of diagnosed, severe, untreated, obstructive sleep apnea.
  • Active substance abuse in the year prior to screening.
  • History of significant sensitivity or allergy to any androgens, including testosterone, or product excipients
  • History of seizures or convulsions, including alcohol or drug withdrawal seizures. Childhood seizures are not exclusionary.
  • 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.
  • 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).
  • 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.
  • 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.
  • Subject who is not willing to use adequate contraception for the duration of the study.
  • Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study.
  • Failure to give informed consent.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • TriWest Research Associates, LLC

    El Cajon, California, 92020

  • R&H Clinical Research

    Katy, Texas, 77494

  • Jubilee Clinical Research, Inc.

    Las Vegas, Nevada, 89106

  • Clinical Research of South Nevada

    Las Vegas, Nevada, 89121

  • Meridien Research-Maitland

    Maitland, Florida, 32751

  • Manassas Clinical Research Center

    Manassas, Virginia, 20110

  • Awasty Research Network

    Marion, Ohio, 43302

  • Tandem Clinical Research

    Marrero, Louisiana, 70072

  • Clinical Pharmacology of Miami, LLC

    Miami, Florida, 33014

  • United Medical Doctors

    Murrieta, California, 92563

  • Sensible Healthcare, LLC

    Ocoee, Florida, 34761

  • Inland Empire Liver Foundation

    Rialto, California, 92377

  • Advanced Clinical Research - Gut Whisperer

    Riverton, Utah, 84065

  • Clinical Trials Research

    Roseville, California, 95661

  • Sun Research Institute

    San Antonio, Texas, 78215

  • Endeavor Clinical Trials

    San Antonio, Texas, 78229

  • Clinical Trial Network-Houston

    Spring, Texas, 77386

  • Pioneer Research Soultions

    Sugar Land, Texas, 77479

  • Granger Medical Clinic

    West Valley City, Utah, 84120

Other trials in United States

About this study

Official title: A Phase 2, Randomized Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis (NASH)

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.

Read the 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.

Being tested
LPCN 1144 Formulation A, LPCN 1144 Formulation B, Placebo
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LPCN 1144 Formulation ADrug

    Also called testosterone undecanoate

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

  • LPCN 1144 Formulation BDrug

    Also called testosterone undecanoate with d-alpha tocopherol

    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

  • PlaceboDrug

    Also called Oral placebo

    Oral matching placebo capsule administered as BID

Study groups in NCT04134091
Study groupRoleWhat they receive
Treatment AExperimentalLPCN 1144 Formulation A
Receives: Drug: LPCN 1144 Formulation A
Treatment BExperimentalLPCN 1144 Formulation B
Receives: Drug: LPCN 1144 Formulation B
Treatment CPlacebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute Change in Hepatic Fat Fraction Based on MRI-PDFF Measurements in LPCN 1144 Treated Subjects Compared to Placebo.

    The change in magnetic resonance imaging derived proton fat fraction (MRI-PDFF) from baseline to week 12 in LPCN 1144 treated subjects and subjects given placebo.

    Measured: Baseline and Week 12

Secondary outcomes (12)

  1. Relative Change in MRI-PDFF Measurements in LPCN 1144 Treated Subjects Compared to Placebo.

    Requirement for inclusion in analysis was having a baseline hepatic fat fraction ≥ 5% based on MRI-PDFF.

    Measured: Baseline and week 12

  2. Number of Participants With Resolution of NASH on Overall Histopathological Reading in LPCN 1144 Treated Subjects Compared to Placebo

    Resolution of nonalcoholic steatohepatitis (NASH) is defined as the nonalcoholic fatty liver disease activity score (NAS) score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis. These data are based on the NASH-clinical research network (CRN) histology scoring system. The range of scores are as follows (with higher scores equating to a more pathological feature): Steatosis 0-3, inflammation 0-3, ballooning 0-2, fibrosis state 0-4, and NAS 0-8.

    Measured: Baseline and Week 36

  3. Number of Subjects Achieving Resolution of NASH on Overall Histopathological Reading and no Worsening of Liver Fibrosis in LPCN 1144 Treated Subjects Compared to Placebo.

    Resolution of NASH is defined as NAS score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis. These data are based on the NASH-CRN histology scoring system. The range of scores are as follows (with higher scores equating to a more pathological feature): Steatosis 0-3, inflammation 0-3, ballooning 0-2, fibrosis state 0-4, and NAS 0-8. No worsening was defined as a score in fibrosis equal to, or lower, than baseline.

    Measured: Baseline and Week 36

  4. Number of Subjects With Improvement in NASH Evaluated by Paired Biopsies Analysis and no Worsening of Liver Fibrosis in LPCN 1144 Treated Subjects Compared to Placebo.

    Paired biopsies are randomly assigned A or B and are scored by a blinded pathologist as better, worse or same for change in fibrosis, steatosis, inflammation, and ballooning. Improvement in NASH requires no worsening of fibrosis, an improvement in ballooning or inflammation, and no worsening of ballooning or inflammation. Assessment of better or same is considered as no worsening.

    Measured: Baseline and week 36

  5. Change in the Mean Score of NAS Components at Baseline and After 36 Weeks of Treatment in LPCN 1144 Treated Subjects Compared to Placebo.

    These data are based on the NASH-CRN histology scoring system. The range of scores are as follows (with higher scores equating to a more pathological feature): Steatosis 0-3, inflammation 0-3, ballooning 0-2, fibrosis state 0-4, and NAS 0-8.

    Measured: Baseline and Week 36

  6. Number of Subjects With an Improvement in Liver Fibrosis Greater Than or Equal to One Stage and no Worsening of NASH in LPCN 1144 Treated Subjects Compared to Placebo.

    These data are based on the NASH-CRN histology scoring system. The range of scores are as follows (with higher scores equating to a more pathological feature): Steatosis 0-3, inflammation 0-3, ballooning 0-2, and fibrosis stage 0-4. Improvement in liver fibrosis was defined as an improvement in fibrosis greater than or equal to one stage using the NASH CRN fibrosis score with no worsening of ballooning, inflammation, or steatosis.

    Measured: Baseline and Week 36

  7. Number of Subjects With Improvement in Fibrosis Evaluated by Paired Biopsies Analysis and no Worsening of NASH in LPCN 1144 Treated Subjects Compared to Placebo

    Paired biopsies are randomly assigned A or B and are scored by a blinded pathologist as better, worse or same for change in fibrosis, steatosis, inflammation, and ballooning. Improvement in fibrosis requires a better score in fibrosis and no worsening of ballooning or inflammation. Assessment of better or same is considered as no worsening.

    Measured: Baseline to week 36

  8. Number of Subjects With Improvement in Fibrosis Evaluated Via FibroNest Scores

    Improvement in Fibrosis is defined as improvement in parenchymal tissue normalized phenotypic fibrosis composite value compared to baseline. FibroNest is an image analysis system for the assessment of the severity and progression of fibrosis in NASH, produced by PharmaNest LLC.

    Measured: Baseline and week 36

  9. Relative Change in Appendicular Lean Muscle Mass

    Relative change in appendicular lean muscle mass measured by dual-energy absorptiometry (DXA) in LPCN 1144 treated subjects compared to Placebo. Data were last observation carried forward.

    Measured: Baseline and 36 weeks

  10. Relative Change in Whole Body Fat Mass

    Relative change in whole body fat mass measured by dual-energy absorptiometry (DXA) in LPCN 1144 treated subjects compared to Placebo. Data were last observation carried forward.

    Measured: Baseline and week 36

  11. Mean Change From Baseline in Liver Enzymes in LPCN 1144 Treated Subjects Compared to Placebo.

    Liver enzymes analyzed were aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT)

    Measured: Baseline and Week 36

  12. Mean Changes in Serum Lipid Profile Parameters in LPCN 1144 Treated Subjects Compared to Placebo.

    Lipid profile parameters included total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides.

    Measured: Baseline and Week 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2019
  2. Study start27 Aug 2019
  3. Primary completion24 Jun 2021
  4. Study completion24 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04134091
Sponsor's protocol ID
LPCN 1144-18-002
Acronym
NASH
Status last verified
Dec 2023
First submitted
16 Aug 2019
Last updated
14 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LPCN 1144 Formulation A and LPCN 1144 Formulation B in people with Nonalcoholic Steatohepatitis (NASH), run by Lipocine Inc. at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change in Hepatic Fat Fraction Based on MRI-PDFF Measurements in LPCN 1144 Treated Subjects Compared to Placebo. (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04134091.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2023.

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