A Study to Assess CYP3A4 Modulator, Oral Contraceptive, and pH Modifier Drug Interactions for ABI-H2158 in Healthy Adults

Sponsor

Assembly Biosciences (Industry)

Overall Status

Completed

CT.gov ID

NCT04142762

Collaborator

(none)

Enrollment

Location

Arms

3.4

Actual Duration (Months)

23.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to assess 1) the effect of multiple doses of itraconazole (CYP3A4 inhibitor), rifampin (CYP3A4 inducer), and esomeprazole (pH modifier) on the pharmacokinetics of a single oral dose of ABI-H2158, and 2) the effect of steady-state oral ABI-H2158 on the pharmacokinetics of midazolam (sedative) and levonorgestrel/ethinyl estradiol (active oral contraceptive) in healthy adult participants.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: ABI-H2158 Drug: Itraconazole Drug: Rifampin Drug: Midazolam Drug: Ethinyl Estradiol / Levonorgestrel Drug: Esomeprazole Drug: Placebo matching oral contraceptive	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-Label, Fixed-Sequence Study to Evaluate CYP3A4-Mediated, Oral Contraceptive, and pH Modifier Drug Interactions for ABI-H2158 in Healthy Adult Subjects

Actual Study Start Date :

Oct 18, 2019

Actual Primary Completion Date :

Jan 12, 2020

Actual Study Completion Date :

Jan 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: ABI-H2158 + Itraconazole Oral ABI-H2158 on Days 1 and 9; oral itraconazole once-daily (QD) on Days 6 through 13	Drug: ABI-H2158 ABI-H2158 tablets Drug: Itraconazole Itraconazole capsules
Experimental: Cohort 2: ABI-H2158 + Rifampin Oral ABI-H2158 on Days 1 and 12; oral rifampin QD on Days 6 through 16	Drug: ABI-H2158 ABI-H2158 tablets Drug: Rifampin Rifampin capsules
Experimental: Cohort 3: ABI-H2158 + Esomeprazole Oral ABI-H2158 on Days 1 and 11; oral esomeprazole QD on Days 6 through 11	Drug: ABI-H2158 ABI-H2158 tablets Drug: Esomeprazole Esomeprazole capsules
Experimental: Cohort 4: ABI-H2158 + Midazolam Oral midazolam on Days 1 and 11; oral ABI-H2158 QD on Days 2 through 11	Drug: ABI-H2158 ABI-H2158 tablets Drug: Midazolam Midazolam syrup
Experimental: Cohort 5: ABI-H2158 + Oral Contraceptive Cycle 1: active oral contraceptive (ethinyl estradiol/levonorgestrel) QD on Days 1 through 21 and oral placebo QD on Days 22 through 28; Cycle 2: active oral contraceptive QD on Days 1 through 21, oral placebo QD on Days 22 through 26, and oral ABI-H2158 QD on Days 11 through 24	Drug: ABI-H2158 ABI-H2158 tablets Drug: Ethinyl Estradiol / Levonorgestrel Ethinyl Estradiol / Levonorgestrel tablets Drug: Placebo matching oral contraceptive Placebo matching Ethinyl Estradiol / Levonorgestrel tablets

Outcome Measures

Primary Outcome Measures

Area under the plasma concentration time curve (AUC) of ABI-H2158 [before dosing and at pre-specified time points up to Day 17]
Maximum observed plasma concentration (Cmax) of ABI-H2158 [before dosing and at pre-specified time points up to Day 17]
AUC of Midazolam [before dosing and at pre-specified time points up to Day 12]
Cmax of Midazolam [before dosing and at pre-specified time points up to Day 17]
AUC of ethinyl estradiol and levonorgestrel [before dosing and at pre-specified time points up to 5 days after dosing on Day 21 of Cycle 1 and Cycle 2. Cycle 1 is 28 days and Cycle 2 is 26 days]
Cmax of ethinyl estradiol and levonorgestrel [before dosing and at pre-specified time points up to 5 days after dosing on Day 21 of Cycle 1 and Cycle 2. Cycle 1 is 28 days and Cycle 2 is 26 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

No clinically significant abnormal findings on physical exam, medical history, or clinical laboratory results at screening.
Cohort 5: naive to the use of oral contraceptives.