Drug-Drug Interaction Study Between EDP-235, Itraconazole, Carbamazepine and Quinidine in Healthy Subjects.

Enanta Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: COVID-19

Treatments: Drug: Itraconazole; Drug: Quinidine; Drug: EDP-235; Drug: Carbamazepine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05594602

EDP 235-002

Details and patient eligibility

About

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

Enrollment: 36 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

EDP-235 and Itraconazole interaction (Part 1)

Experimental group

Description:

Subjects will receive EDP-235 and Itraconazole on respective dosing days

Treatment:

Drug: EDP-235

Drug: EDP-235

Drug: EDP-235

Drug: Itraconazole

EDP-235 and Carbamazepine interaction (Part 2)

Experimental group

Description:

Subjects will receive EDP-235 and Carbamazepine on respective dosing days

Treatment:

Drug: EDP-235

Drug: EDP-235

Drug: Carbamazepine

Drug: EDP-235

EDP and Quinidine interaction (Part 3)

Experimental group

Description:

Subjects will receive EDP-235 and Quinidine on respective dosing days

Treatment:

Drug: Quinidine

Drug: EDP-235

Drug: EDP-235

Drug: EDP-235