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

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

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: EDP-235
* Drug: EDP-235
* Drug: EDP-235
* Drug: Itraconazole
* Drug: Carbamazepine
* Drug: Quinidine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug-drug interaction