A Study of EDP 305 in Healthy Subjects and Subjects With Presumptive NAFLD

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.

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 Exclusion Criteria for MAD Subjects with Presumptive NAFLD:

• Subjects taking any antidiabetic medication.
• Subjects with unstable proliferative retinopathy, macular oedema (fundus examination performed in the previous year will be considered relevant on Investigator's judgement).
• Subject has taken fibrates, statins, and/or Vitamin E within 6 weeks prior to the first dose administration.
• Subjects with a history of bariatric surgery and any other gastrointestinal surgery relative to weight loss.
• Subjects with common causes of secondary hepatic steatosis.