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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
56
Oral LPCN 1144 Formulation A capsule, total daily dose of 450 mg testosterone undecanoate administered as 225 mg testosterone undecanoate twice daily (BID).
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
Oral matching placebo capsule administered as BID
TriWest Research Associates, LLC
El Cajon, California, United States
United Medical Doctors
Murrieta, California, United States
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.
Time frame: Baseline and Week 12
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.
Time frame: Baseline and week 12
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.
Time frame: Baseline and Week 36
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.
Time frame: Baseline and Week 36
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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
...and 9 more locations
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.
Time frame: Baseline and week 36
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.
Time frame: Baseline and Week 36
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.
Time frame: Baseline and Week 36
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.
Time frame: Baseline to week 36
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.
Time frame: Baseline and week 36
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.
Time frame: Baseline and 36 weeks
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.
Time frame: Baseline and week 36
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)
Time frame: Baseline and Week 36
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.
Time frame: Baseline and Week 36