Clinical trial NCT05594602: Drug-Drug Interaction Study Between EDP-235, Itraconazole, Carbamazepine and Quinidine in Healthy Subjects.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Keywords: drug-drug interaction
Lead sponsor: Enanta Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2022-10-26
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Cmax of EDP-235 with and without coadministration with Itraconazole
timeFrame: Day 1 through Day 19
measure: AUC of EDP-235 with and without coadministration with Itraconazole
timeFrame: Day 1 through Day 19
measure: Cmax of EDP-235 with and without coadministration with Carbamazepine
timeFrame: Day 1 through Day 26
measure: AUC of EDP-235 with and without coadministration with Carbamazepine
timeFrame: Day 1 through Day 26
measure: Cmax of EDP-235 with and without coadministration with Quinidine
timeFrame: Day 1 through Day 13
measure: AUC of EDP-235 with and without coadministration with Quinidine
timeFrame: Day 1 through Day 13
Secondary outcomes:
measure: Safety measured by adverse events
timeFrame: Up to 34 days
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: ICON, plc.
state: Kansas
Study officials:
affiliation: Enanta Pharmaceuticals, Inc
name: Enanta Pharmaceuticals, Inc
role: STUDY_DIRECTOR
References: