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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study of Orally Administered EDP-305 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (SAD), Multiple Ascending Doses (MAD) and the Effect of Food on EDP-305 Pharmacokinetics in Healthy Subjects, and of Multiple Ascending Doses (MAD) in Subjects With Presumptive NAFLD

Conditions
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Presumptive NAFLD

Intervention / Treatment
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* Drug: EDP 305
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EDP 305 SAD Cohorts<br>EDP 305 Dose 1, Dose 2, Dose 3, Dose 4, Dose 5, and Dose 6 oral suspension, once daily in one single administration | Drug: EDP 305<br> <br> |
| Experimental: EDP 305 MAD Cohorts<br>EDP 305 Dose 1, Dose 2, Dose 3, Dose 4, Dose 5 and Dose 6 oral suspension, once daily for 14 days | Drug: EDP 305<br> <br> |
| Placebo Comparator: EDP 305 SAD Placebo Cohort<br>Matching placebo, oral suspension, once daily in one single administration | Drug: Placebo<br>* placebo to match EDP 305<br>|
| Placebo Comparator: EDP 305 MAD Placebo Cohort<br>Matching placebo, oral suspension, once daily for 14 days | Drug: Placebo<br>* placebo to match EDP 305<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | EDP 305 | 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. | 
| Cmax | EDP 305 | Day 1: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15 hrs; Days 2, 3, 4, 5, 7, 9, 12; Day 14: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24 (D15), 30, 36, 48 (D16), 60, 72 (D17), and 96 (D18) hrs postdose | 
| AUC | EDP 305 | 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. | 
| AUC | EDP 305 | Day 1: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15 hrs; Days 2, 3, 4, 5, 7, 9, 12; Day 14: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24 (D15), 30, 36, 48 (D16), 60, 72 (D17), and 96 (D18) hrs postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-in-human, Single Ascending Dose, Multiple Ascending Dose