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.

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