Drug-Drug Interaction Study Between EDP-514, Itraconazole, Carbamazepine, and Quinidine in Healthy Subjects

A Non-Randomized, Open-Label, Three-Part, Drug-Drug Interaction Study to Evaluate the Effects of Itraconazole, Carbamazepine, and Quinidine on the Pharmacokinetics and Safety of EDP-514 in Healthy Subjects

Non-randomized, 3-part, open-label, drug-drug interaction (DDI) study to evaluate the effect of itraconazole, carbamazepine, or quinidine on the PK and safety of EDP-514 in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: EDP-514; Drug: EDP-514; Drug: EDP-514; Drug: Itraconazole; Drug: Carbamazepin; 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 Association

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• An informed consent document signed and dated by the subject.
• Male and female subjects of any ethnic origin between the ages of 18 and 55 years, inclusive
• Female subjects who are heterosexually active and of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 30 days after the last dose of EDP-514.
• Screening body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg.

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 clinically significant active infection.
• A positive urine drug screen at Screening or Day -1.
• Current tobacco smokers or use of tobacco products within 3 months prior to Screening.

• Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy).

  • Clinically significant laboratory abnormalities at screening or Day -1, as determined by the Investigator (including but not limited to hypokalemia, hypocalcemia, or hypomagnesemia for Part 3 participants).

• History of regular alcohol consumption
• Participation in a clinical trial within 30 days prior to the first dose of study drug.

For Part 2 (Carbamazepine) participants:

• Participants of Asian ancestry, given association of carbamazepine and severe rash (Stevens Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) with HLA-B 1502 in this population.
• Platelets, white blood cell count or hemoglobin below the lower limit of normal, due to reported incidence of agranulocytosis and aplastic anemia with carbamazepine.

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-514 and Itraconazole interaction (Part 1)	Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 14; Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 23; Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 8; Drug: Itraconazole; Subjects will receive itraconazole QD for 14 days
Experimental: EDP-514 and Carbamazepine interaction (Part 2)	Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 14; Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 23; Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 8; Drug: Carbamazepin; Subjects will receive carbamazepine BID for 23 days
Experimental: EDP-514 and Quinidine interaction (Part 3)	Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 14; Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 23; Drug: EDP-514; Subjects will receive EDP-514 on Days 1 and 8; Drug: Quinidine; Subjects will receive quinidine BID for 8 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of EDP-514 with and without coadministration with itraconazole	up to 19 days
AUC of EDP-514 with and without coadministration with itraconazole	19 days
Cmax of EDP-514 with and without coadministration with carbamazepine	up to 28 days
AUC of EDP-514 with and without coadministration with carbamazepine	up to 28 days
Cmax of EDP-514 with and without coadministration with quinidine	up to 13 days
AUC of EDP-514 with and without coadministration with quinidine	up to 13 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: PRA Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Actual): June 28, 2021
• Study Completion (Actual): July 9, 2021

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 13, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: drug-drug interaction
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones, Hormone Substitutes, and Hormone Antagonists; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antimanic Agents; 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; Antimalarials; 14-alpha Demethylase Inhibitors; Adrenergic alpha-Antagonists; Itraconazole; Carbamazepine; Quinidine
• Other Study ID Numbers: EDP 514-003

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