Drug-Drug Interaction Study Between EDP-235, 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-235 IN HEALTHY PARTICIPANTS

A Drug-Drug Interaction study to assess the effects of itraconazole, carbamazepine and quinidine on the Pharmacokinetics and Safety of EDP-235.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: EDP-235; Drug: EDP-235; Drug: EDP-235; Drug: Itraconazole; Drug: Carbamazepine; Drug: Quinidine

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • ICON, plc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

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-235. A male participant who has not had a vasectomy and is sexually active with a woman of childbearing potential must agree to use effective contraception from the date of Screening to 90 days after his last dose of study drug.

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 2 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.

• For Part 2 and Part 3 participants, 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
• History of drug allergy to itraconazole or other azole antifungals; history of drug allergy to carbamazepine or carboxamide derivatives [e.g. oxcarbazepine]; known hypersensitivity to drugs structurally related to carbamazepine [e.g.: tricyclic antidepressants] or any of its excipients);history or known hypersensitivity to mefloquine, quinine, or quinidine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDP-235 and Itraconazole interaction (Part 1); Subjects will receive EDP-235 and Itraconazole on respective dosing days	Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 14; Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 23; Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 8; Drug: Itraconazole; Subjects will receive itraconazole QD Days 5-18
Experimental: EDP-235 and Carbamazepine interaction (Part 2); Subjects will receive EDP-235 and Carbamazepine on respective dosing days	Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 14; Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 23; Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 8; Drug: Carbamazepine; Subjects will receive carbamazepine BID Days 5-23 and Days 24-27
Experimental: EDP and Quinidine interaction (Part 3); Subjects will receive EDP-235 and Quinidine on respective dosing days	Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 14; Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 23; Drug: EDP-235; Subjects will receive EDP-235 on Days 1 and 8; Drug: Quinidine; Subjects will receive quinidine BID Days 5-12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of EDP-235 with and without coadministration with Itraconazole	Day 1 through Day 19
AUC of EDP-235 with and without coadministration with Itraconazole	Day 1 through Day 19
Cmax of EDP-235 with and without coadministration with Carbamazepine	Day 1 through Day 26
AUC of EDP-235 with and without coadministration with Carbamazepine	Day 1 through Day 26
Cmax of EDP-235 with and without coadministration with Quinidine	Day 1 through Day 13
AUC of EDP-235 with and without coadministration with Quinidine	Day 1 through Day 13

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2022
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: October 21, 2022
• First Submitted That Met QC Criteria: October 21, 2022
• First Posted (Actual): October 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: drug-drug interaction
• Additional Relevant MeSH Terms: 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 235-002

Drug and device information, study documents

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