Drug-Drug Interaction Study Between EDP-938, Tacrolimus, Dabigatran, Rosuvastatin and Midazolam in Healthy Subjects

A Non-Randomized, Open-Label, Three-Part, Drug-Drug Interaction Study to Evaluate the Effects of EDP-938 on the Pharmacokinetics of Tacrolimus, Dabigatran, Rosuvastatin and Midazolam in Healthy Subjects

A Non-Randomized, Open-Label, Three-Part, Drug-Drug Interaction Study to Evaluate the Effects of tacrolimus, dabigatran, rosuvastatin and midazolam on the Pharmacokinetics and Safety of EDP-938 in Healthy Subjects

Study Overview

• Status: Completed
• Conditions: RSV Infection
• Intervention / Treatment: Drug: EDP-938; Drug: EDP-938; Drug: EDP-938; Drug: Tacrolimus; Drug: EDP-938; Drug: Dabigatran; Drug: Rosuvastatin; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Pharmaceutical Research Associates, Inc.,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.
• Screening body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg
• Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP 938.

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 the first dose of study drug.
• For Part 1 subjects:
• Clinical history or evidence at Screening consistent with hyperkalemia, hypertension and/or diabetes mellitus
• For Part 2 Subjects:
• Clinical history or evidence at screening of medically significant bleeding
• History of a mechanical heart valve placement, a thromboembolic event or clinically significant thrombotic event, an autoimmune disease, eg, systemic lupus erythematosus (SLE), or recurrent spontaneous abortions
• A platelet count <LLN, or INR >ULN, or aPTT > ULN at Screening
• Ongoing daily use of nonsteroidal anti-inflammatory drugs
• For Part 3 subjects:
• AST and/or ALT >ULN at Screening
• For Part 4 subjects:
• History of glaucoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDP-938 and tacrolimus interaction (Part 1)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 10 through 27 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 3); Drug: Tacrolimus; Subjects will receive tacrolimus once daily on Day 1 and Day 24; Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 3 through 16 (Part 4)
Experimental: EDP-938 and dabigatran interaction (Part 2)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 10 through 27 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 3); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 3 through 16 (Part 4); Drug: Dabigatran; Subjects will receive dabigatran once daily on Day 1 and Day 13
Experimental: EDP-938 and rosuvastatin interaction (Part 3)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 10 through 27 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 3); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 3 through 16 (Part 4); Drug: Rosuvastatin; Subjects will receive rosuvastatin once daily on Day 1 and Day 13
Experimental: EDP-938 and midazolam interaction (Part 4)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 10 through 27 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 5 through 15 (Part 3); Drug: EDP-938; Subjects will receive EDP-938 once daily on Days 3 through 16 (Part 4); Drug: Midazolam; Subjects will receive midazolam once daily on Day 1 and Day 16

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of tacrolimus with and without coadministration with EDP-938	up to 29 days
AUC of tacrolimus with and without coadministration with EDP-938	up to 29 days
Cmax of dabigatran with and without coadministration with EDP-938	up to 17 days
AUC of dabigatran with and without coadministration with EDP-938	up to 17 days
Cmax of rosuvastatin with and without coadministration with EDP-938	up to 17 days
AUC of rosuvastatin with and without coadministration with EDP-938	up to 17 days
Cmax of midazolam with and without coadministration with EDP-938	up to 17 days
AUC of midazolam with and without coadministration with EDP-938	up to 17 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety measured by adverse events	up to 34 days

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc
• Collaborators: Pharmaceutical Research Associates

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Actual): May 27, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: drug-drug interaction
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antimetabolites; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Calcineurin Inhibitors; Midazolam; Dabigatran; Rosuvastatin Calcium; Tacrolimus
• Other Study ID Numbers: EDP 938-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No