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

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: ABI-H2158; Drug: Ethinyl Estradiol / Levonorgestrel; Drug: Itraconazole; Drug: Rifampin; Drug: Esomeprazole; Drug: Midazolam; Drug: Placebo matching oral contraceptive

• Registration Number: NCT04142762
• Lead Sponsor: Assembly Biosciences

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-16
• Study Start: 2019-10-18
• Study First Submitted QC: 2019-10-26
• Study First Posted: 2019-10-29
• Primary Completion: 2020-01-12
• Study Completion: 2020-01-29
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-03
• Last Update Posted: 2020-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

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

Exclusion Criteria

1. Positive test results for human immunodeficiency virus (HIV) or hepatitis B or C.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2: ABI-H2158 + Rifampin	ABI-H2158	Oral ABI-H2158 on Days 1 and 12; oral rifampin QD on Days 6 through 16
Cohort 5: ABI-H2158 + Oral Contraceptive	ABI-H2158	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
Cohort 5: ABI-H2158 + Oral Contraceptive	Ethinyl Estradiol / Levonorgestrel	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
Cohort 5: ABI-H2158 + Oral Contraceptive	Placebo matching 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
Cohort 3: ABI-H2158 + Esomeprazole	ABI-H2158	Oral ABI-H2158 on Days 1 and 11; oral esomeprazole QD on Days 6 through 11
Cohort 1: ABI-H2158 + Itraconazole	ABI-H2158	Oral ABI-H2158 on Days 1 and 9; oral itraconazole once-daily (QD) on Days 6 through 13
Cohort 4: ABI-H2158 + Midazolam	ABI-H2158	Oral midazolam on Days 1 and 11; oral ABI-H2158 QD on Days 2 through 11
Cohort 1: ABI-H2158 + Itraconazole	Itraconazole	Oral ABI-H2158 on Days 1 and 9; oral itraconazole once-daily (QD) on Days 6 through 13
Cohort 2: ABI-H2158 + Rifampin	Rifampin	Oral ABI-H2158 on Days 1 and 12; oral rifampin QD on Days 6 through 16
Cohort 3: ABI-H2158 + Esomeprazole	Esomeprazole	Oral ABI-H2158 on Days 1 and 11; oral esomeprazole QD on Days 6 through 11
Cohort 4: ABI-H2158 + Midazolam	Midazolam	Oral midazolam on Days 1 and 11; oral ABI-H2158 QD on Days 2 through 11

Primary Outcome Measures

Name	Time	Method
Cmax of Midazolam	before dosing and at pre-specified time points up to Day 17
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
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

Trial Locations

Locations (1)

Celerion; 🇺🇸 Tempe, Arizona, United States