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

Study Overview
=================
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.

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

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: ABI-H2158
* Drug: Itraconazole
* Drug: Rifampin
* Drug: Midazolam
* Drug: Ethinyl Estradiol / Levonorgestrel
* Drug: Esomeprazole
* Drug: Placebo matching oral contraceptive


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Exclusion Criteria: 1. Positive test results for human immunodeficiency virus (HIV) or hepatitis B or C.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ABI-H2158 + Itraconazole<br>Oral ABI-H2158 on Days 1 and 9; oral itraconazole once-daily (QD) on Days 6 through 13 | Drug: ABI-H2158<br>* ABI-H2158 tablets<br>Drug: Itraconazole<br>* Itraconazole capsules<br>|
| Experimental: Cohort 2: ABI-H2158 + Rifampin<br>Oral ABI-H2158 on Days 1 and 12; oral rifampin QD on Days 6 through 16 | Drug: ABI-H2158<br>* ABI-H2158 tablets<br>Drug: Rifampin<br>* Rifampin capsules<br>|
| Experimental: Cohort 3: ABI-H2158 + Esomeprazole<br>Oral ABI-H2158 on Days 1 and 11; oral esomeprazole QD on Days 6 through 11 | Drug: ABI-H2158<br>* ABI-H2158 tablets<br>Drug: Esomeprazole<br>* Esomeprazole capsules<br>|
| Experimental: Cohort 4: ABI-H2158 + Midazolam<br>Oral midazolam on Days 1 and 11; oral ABI-H2158 QD on Days 2 through 11 | Drug: ABI-H2158<br>* ABI-H2158 tablets<br>Drug: Midazolam<br>* Midazolam syrup<br>|
| Experimental: Cohort 5: ABI-H2158 + Oral Contraceptive<br>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<br>* ABI-H2158 tablets<br>Drug: Ethinyl Estradiol / Levonorgestrel<br>* Ethinyl Estradiol / Levonorgestrel tablets<br>Drug: Placebo matching oral contraceptive<br>* Placebo matching Ethinyl Estradiol / Levonorgestrel tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |