Drug-Drug Interaction Study Between EDP-938, Itraconazole, Rifampin, and Quinidine in Healthy Subjects

A Non-Randomized, Open-Label, Three-Part, Drug-Drug Interaction Study to Evaluate the Effects of Itraconazole, Rifampin, and Quinidine on the Pharmacokinetics and Safety of EDP-938 in Healthy Subjects

A Non-Randomized, Open-Label, Three-Part, Drug-Drug Interaction Study to Evaluate the Effects of Itraconazole, Rifampin, and Quinidine 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: Itraconazole; Drug: Rifampin; Drug: Quinidine

• Study Type: Interventional
• Enrollment (Actual): 72
• 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.

• For Part 3 subjects, the following cardiovascular abnormalities:

  • QRS duration >110 ms
  • Incomplete right bundle branch block or any complete bundle branch block
  • Heart rate <40 or >90 beats per minute (per vital sign capture while rested)
  • History of unexplained syncope, structural heart disease, or clinically significant arrhythmias
  • Personal or family history of long QT syndrome (genetically proven or suggested by sudden death of a close relative due to cardiac causes at a young age) or Brugada syndrome
  • PR interval >220 ms or any 2nd or 3rd degree AV block
  • Ventricular pre-excitation
• 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.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDP-938 and itraconazole interaction (Part 1)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 14 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 14 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 8 (Part 3); Drug: Itraconazole; Subjects will receive itraconazole once daily from Day 5 to Day 18
Experimental: EDP-938 and rifampin interaction (Part 2)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 14 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 14 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 8 (Part 3); Drug: Rifampin; Subjects will receive rifampin once daily from Day 5 to Day 16
Experimental: EDP-938 and quinidine interaction (Part 3)	Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 14 (Part 1); Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 14 (Part 2); Drug: EDP-938; Subjects will receive EDP-938 once daily on Day 1 and 8 (Part 3); Drug: Quinidine; Subjects will receive quinidine once daily from Day 5 to Day 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of EDP-938 with and without coadministration with itraconazole	Up to 19 days
AUC of EDP-938 with and without coadministration with itraconazole	Up to 19 days
Cmax of EDP-938 with and without coadministration with rifampin	Up to 17 days
AUC of EDP-938 with and without coadministration with rifampin	Up to 17 days
Cmax of EDP-938 with and without coadministration with quinidine	Up to 13 days
AUC of EDP-938 with and without coadministration with quinidine	Up to 13 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety measured by adverse events	Up to 25 days

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc
• Collaborators: Pharmaceutical Research Associates
• Investigators: Study Director: Enanta Pharmaceuticals, Enanta Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2018
• Primary Completion (Actual): January 21, 2019
• Study Completion (Actual): January 27, 2019

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: October 1, 2018

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; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antimalarials; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Adrenergic alpha-Antagonists; Rifampin; Itraconazole; Quinidine
• Other Study ID Numbers: EDP 938-003

Drug and device information, study documents

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