Study of Gemcabene in Adults With FPLD

NCT03508687 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HUM00130803
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this study is to assess the efficacy and safety of two dosing regimens of gemcabene (300 mg once daily for 24 weeks or 300 mg daily for 12 weeks followed by 600 mg daily for 12 weeks) in up to eight patients with Familial Partial Lipodystrophy with high triglycerides and Non-Alcoholic Fatty Liver Disease. The study will consist of a six week Wash Out Period, up to a 28 day Screening Period, a 24 week Treatment Period, and a follow-on safety assessment four weeks post final dose. Study participation will last approximately 4 months and includes at least 9 study visits, and can be as many as 11 study visits.

Conditions

Familial Partial Lipodystrophy; Hypertriglyceridemia; Fatty Liver; NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Change in Fasting Serum Triglyceride (at 12 Weeks)

  This is measured by percent change in fasting serum triglyceride from baseline to week 12

  Baseline to week 12

Secondary Outcomes (18)

• Change in Fasting Serum Triglycerides (Through 24 Weeks)

  Baseline, week 6 and week 12, week 24

• Percent Change in Fasting Serum Triglycerides (Through 24 Weeks)

  Baseline, week 6 and week 12, week 24

• Change in Liver Fat Content as Measured by Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF)

  Baseline, week 12, week 24

• Percent Change in Liver Fat Content as Measured by Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF)

  Baseline, week 12, week 24

• Change in Liver Fibrosis

  Baseline, Week 12, and Week 24

Study Arms (2)

Group 1: 300 mg Gemcabene daily week 12-24

EXPERIMENTAL

Patients took Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients were randomized 1:1 according to pre-generated randomization code. This arm received 300mg Gemcabene daily for 12 weeks total, starting at week 12.

Drug: 300mg Gemcabene

Group 2: 600mg Gemcabene daily week 12-24

EXPERIMENTAL

Patients took Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients were randomized 1:1 according to pre-generated randomization code. This arm received 600mg Gemcabene daily for 12 weeks total, starting at week 12.

Drug: 600mg Gemcabene

Interventions

300mg Gemcabene DRUG

300mg Gemcabene

Group 1: 300 mg Gemcabene daily week 12-24

600mg Gemcabene DRUG

600mg Gemcabene

Group 2: 600mg Gemcabene daily week 12-24

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* Clinical diagnosis of lipodystrophy based on a lack of body fat in a partial fashion assessed by physical examination, and at least 1 MAJOR criterion (below): * Low skinfold thickness in anterior thigh by caliper measurement: men (≤ 10 mm) and women (≤ 22 mm) OR * Historic genetic diagnosis of familial partial lipodystrophy (e.g. mutations in LMNA, PPAR-γ, AKT2, or PLIN1 genes) as supported by source documentation * Hepatic steatosis (\>10% - Stage 2 or 3) as demonstrated by MRI-PDFF; * Alcohol intake of less than 20 g per day in females and 30 g per day in males (one 12 oz beer, one glass of wine, or 2 oz of spirits or liquor equals roughly 10 g of alcohol; * Mean fasting triglyceride value ≥ 250 mg/dL at the Screening Visit; * Background lipid lowering medications must be stable for at least 6 weeks prior to the Screening Visit; * Women patients must not be pregnant or lactating and women of child-bearing potential must agree to use acceptable methods of contraception throughout the duration of the study and for 30 days after the last dose of study drug. Male patients must agree to use contraception by means of a condom and may not donate sperm throughout the duration of the study and for 8 days after the last dose of study drug. * Weight greater than 50 kg (\~110 lbs); with a body mass index (BMI) of no more than 45 kg/m²; * Have not used a fibrate with in the last 6 weeks and/or thiazolidinediones (TZDs) within the last 12 weeks prior to the Screening visit. * Do not have a hypersensitivity or a history of significant reactions of fibrates. * Are not currently taking potent CYP3A4 inhibitors such as itraconazole or a macrolide antibiotic. * Have a condition or finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Elif Oral: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

MeSH Terms

Conditions

Lipodystrophy, Familial Partial; Hypertriglyceridemia; Fatty Liver; Non-alcoholic Fatty Liver Disease

Interventions

gemcabene

Condition Hierarchy (Ancestors)

Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Liver Diseases; Digestive System Diseases

Limitations and Caveats

The expected number of study subjects (8), was not reached.

Results Point of Contact

• Title: Dr. Elif Oral
• Organization: University of Michigan

eliforal@med.umich.edu

734-615-7271

Study Officials

• Elif A Oral, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 3, 2018
• First Posted: April 26, 2018
• Study Start: March 13, 2018
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: August 17, 2020
• Results First Posted: August 17, 2020

Record last verified: 2020-07

Locations

US (1)