Presumptive NAFLD
Conditions
Keywords
First-in-human, Single Ascending Dose, Multiple Ascending Dose
Brief summary
This randomized, double-blind, placebo-controlled study will assess the safety, tolerability, and pharmacokinetics of single and multiple orally administered doses of EDP-305 in healthy adult subjects, and adult subjects with presumptive NAFLD (i.e., obese subjects with or without prediabetes or T2DM).
Detailed description
The first phase assesses single ascending doses for EDP 305 (active drug or placebo) in healthy subjects. A fasted and fed two-part cohort will also assess food effect. The second phase assesses multiple ascending doses (active drug or placebo) for 14-days in healthy subjects and also in subjects with presumptive NAFLD (i.e., obese subjects with or without prediabetes or T2DM). Each cohort within each phase will enroll a total of 8 subjects who will be randomized to receive EDP-305 or placebo. The cohort assessing food effect will enroll 10 subjects randomized to receive EDP-305 or placebo.
Interventions
DRUGPlacebo
placebo to match EDP 305
DRUGEDP 305
Sponsors
Pharmaceutical Research Associates
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
for all SAD and MAD Subjects:: * An informed consent document signed and dated by the subject. * Healthy male and female subjects of any ethnic origin between the ages of 18 and 55 years, inclusive. * Female subjects must be of non-childbearing potential. * All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug. * For healthy volunteers only (see below for Subjects with presumptive NAFLD): Body mass index of 18 to 30 kg/m2 with a minimum body weight of 50 kg. Additional Inclusion Criteria for MAD Subjects with Presumptive NAFLD: * Body mass index of \>28 and \<35 kg/m2 at screening. WITH or WITHOUT one of the following: * Type 2 diabetes mellitus diagnosed by one of the following methods: * As defined by the American Diabetes Association (ADA), as one of the following criteria: a) symptoms of diabetes plus casual plasma glucose concentration \>200 mg/dL (11.1 mmol/L) OR b) Fasting plasma glucose \>126 mg/dL (7.0 mmol/L) OR c) 2-hour post-load glucose \>200 mg/dL (11.1 mmol/L) during a 75 g oGTT. * HbA1c of at least 6.5%. --- OR--- * Prediabetes diagnosed as defined by the ADA as a) an HbA1c of 5.7% - 6.4% OR b) fasting blood glucose of 100-125 mg/dL OR c) an oGTT 2-hour blood glucose of 140 mg/dL - 199 mg/dL.
Exclusion criteria
* Clinically relevant evidence or history of illness or disease. * Pregnant or nursing females. * History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection. * A positive urine drug screen at screening or Day -1. * Current tobacco smokers or use of tobacco within 3 months prior to screening. * Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy). * History of regular alcohol consumption * Participation in a clinical trial within 30 days prior to study drug administration. * Use of prescription drugs, non-prescription drugs, dietary supplements including Vitamin E herbal supplements, hormonal therapy/replacement or CYP3A4 substrates, inducers and inhibitors within 14 days prior to the first dose of study medication. Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety data including but not limited to adverse events, physical exams, vital signs, 12-lead ECGs and clinical lab results (including chemistry, hematology, and urinalysis). | From screening to the 7-day post treatment safety follow up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72 (D4), and 96 (D5) hrs post dose. | EDP 305 |
| AUC | 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72 (D4), and 96 (D5) hrs post dose. | EDP 305 |
Other
| Measure | Time frame |
|---|---|
| Change from baseline: FGF19 | Day 1 predose and postdose hours 2, 4, 8, 12, and 24 (i.e., Day 2 predose) |
| Change from baseline: C4 | Day 1 predose and postdose hours 2, 4, 8, 12, and 24 (i.e., Day 2 predose) |
| Change from baseline: total bile acids | Day 1 predose and approximately 8 to 12 hours postdose |
Countries
United States
Outcome results
None listed