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

Primary Purpose

Liver Cirrhosis, Sarcopenia

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LPCN 1148
Placebo
Sponsored by
Lipocine Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • University of California, Los Angeles
  • University of California San Francisco
  • University of Maryland Medical Center
  • Beth Israel Deaconess Medical Center
  • Methodist Health System
  • University of Texas Southwestern
  • Mt.Olympus Medical Research
  • Intermountain Healthcare
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LPCN 1148

Placebo

Arm Description

Oral LPCN 1148 capsules, administered as BID.

Oral matching placebo capsules, administered as BID.

Outcomes

Primary Outcome Measures

Change from baseline in Skeletal Muscle Index in LPCN 1148 treated subjects compared to placebo

Secondary Outcome Measures

Change from baseline in Liver Frailty Index in LPCN 1148 treated subjects compared to placebo
Change in number of waitlist events in LPCN 1148 treated subjects compared to placebo
Change in number of hepatic encephalopathy events in LPCN 1148 treated subjects compared to placebo

Full Information

First Posted
May 3, 2021
Last Updated
December 19, 2022
Sponsor
Lipocine Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04874350
Brief Title
A Study to Assess the Efficacy, Safety, and Tolerability of Oral LPCN 1148 in Male Subjects With Cirrhosis of the Liver and Sarcopenia
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 20, 2021 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lipocine Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis, Sarcopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized 1:1 to LPCN 1148 or placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LPCN 1148
Arm Type
Experimental
Arm Description
Oral LPCN 1148 capsules, administered as BID.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral matching placebo capsules, administered as BID.
Intervention Type
Drug
Intervention Name(s)
LPCN 1148
Intervention Description
LPCN 1148 is an oral capsule product containing an ester prodrug of bioidentical testosterone, designed to enable absorption via intestinal lymphatics.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral matching placebo capsule
Primary Outcome Measure Information:
Title
Change from baseline in Skeletal Muscle Index in LPCN 1148 treated subjects compared to placebo
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change from baseline in Liver Frailty Index in LPCN 1148 treated subjects compared to placebo
Time Frame
Up to 52 weeks
Title
Change in number of waitlist events in LPCN 1148 treated subjects compared to placebo
Time Frame
Up to 52 weeks
Title
Change in number of hepatic encephalopathy events in LPCN 1148 treated subjects compared to placebo
Time Frame
Up to 52 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male ≥ 18 years old 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) Evidence of sarcopenia with appropriate cutoff recommended by clinical guidance Exclusion Criteria: Suspected or proven hepatocellular carcinoma (HCC) History of current or suspected prostate or breast cancer 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) 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. History or current thrombosis (including portal vein thrombosis), thromboembolism, or treatment for portal vein thrombosis History of hemochromatosis 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) Prior history of complications of ascites in the past 6 months including: Spontaneous bacterial peritonitis Hepatic hydrothorax MELD score > 25 Abnormal lab value in serum chemistry, hematology, or urinalysis that the PI considers clinically significant, including but not limited to: PSA > 4 ng/mL Polycythemia (Hematocrit > ULN) or history of polycythemia ALT or AST > 5x ULN ALP > 2x ULN; subjects with PBC or PSC are excluded if ALP is > 10x ULN Platelet count < 30,000/mL EGFR < 30 mL/min/1.73 m2 for subjects not undergoing routine, scheduled dialysis Serum albumin < 2.0 g/dL INR > 2.3 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: Hematocrit > 48% I-PSS > 19 Any irregularity found on digital rectal examination of the prostate Subjects with PSA > 3 ng/mL are excluded only if any of the below criteria are met at baseline: Subject is African American Subject has a first-degree relative who has a history of prostate cancer Hematocrit > 48% I-PSS > 19 Any irregularity found on digital rectal examination of the prostate 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 History of bariatric surgery History of stroke or myocardial infarction within the past 5 years History of TIPS within the past 6 months, or TIPS procedure expected within 6 months of Day 1 Known positivity for Human Immunodeficiency Virus (HIV) infection Acute liver failure as the indication for addition to the liver transplant waitlist Estimated life expectancy less than 3 months or expected to undergo liver transplant within 3 months Known heart failure of New York Heart Association class III or IV Evidence of severe encephalopathy at screening encephalopathy that is not controlled despite adequate medical therapy History of prior organ transplant History of Fontan physiology History of pulmonary embolus Porto-pulmonary hypertension Hepatopulmonary syndrome requiring standing home supplemental oxygen therapy, or MELD exception points for hepatopulmonary syndrome Uncontrolled epilepsy or migraine Active substance abuse or dependency extending to within the previous 3 months History of significant sensitivity or allergy to testosterone, or product excipients. 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-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 Uncontrolled hypertension (>160/90 mmHg despite treatment) Uncontrolled obstructive sleep apnea 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 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 to the study protocol (including diet, exercise, and alcohol abstinence) or hinder completion of the study Failure to give informed consent
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Methodist Health System
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
University of Texas Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75309
Country
United States
Facility Name
Mt.Olympus Medical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Intermountain Healthcare
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

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

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