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

NCT04142762 | Completed Phase 1 FDA Drug

• 1 other identifier: ABI-H2158-103
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (5)

Cohort 1: ABI-H2158 + Itraconazole

EXPERIMENTAL

Oral ABI-H2158 on Days 1 and 9; oral itraconazole once-daily (QD) on Days 6 through 13

Drug: ABI-H2158; Drug: Itraconazole

Cohort 2: ABI-H2158 + Rifampin

EXPERIMENTAL

Oral ABI-H2158 on Days 1 and 12; oral rifampin QD on Days 6 through 16

Drug: ABI-H2158; Drug: Rifampin

Cohort 3: ABI-H2158 + Esomeprazole

EXPERIMENTAL

Oral ABI-H2158 on Days 1 and 11; oral esomeprazole QD on Days 6 through 11

Drug: ABI-H2158; Drug: Esomeprazole

Cohort 4: ABI-H2158 + Midazolam

EXPERIMENTAL

Oral midazolam on Days 1 and 11; oral ABI-H2158 QD on Days 2 through 11

Drug: ABI-H2158; Drug: Midazolam

Cohort 5: ABI-H2158 + Oral Contraceptive

EXPERIMENTAL

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; Drug: Ethinyl Estradiol / Levonorgestrel; Drug: Placebo matching oral contraceptive

Interventions

ABI-H2158 DRUG

ABI-H2158 tablets

Cohort 1: ABI-H2158 + Itraconazole; Cohort 2: ABI-H2158 + Rifampin; Cohort 3: ABI-H2158 + Esomeprazole; Cohort 4: ABI-H2158 + Midazolam; Cohort 5: ABI-H2158 + Oral Contraceptive

Itraconazole DRUG

Itraconazole capsules

Cohort 1: ABI-H2158 + Itraconazole

Rifampin DRUG

Rifampin capsules

Cohort 2: ABI-H2158 + Rifampin

Midazolam DRUG

Midazolam syrup

Cohort 4: ABI-H2158 + Midazolam

Ethinyl Estradiol / Levonorgestrel DRUG

Ethinyl Estradiol / Levonorgestrel tablets

Cohort 5: ABI-H2158 + Oral Contraceptive

Esomeprazole DRUG

Esomeprazole capsules

Cohort 3: ABI-H2158 + Esomeprazole

Placebo matching oral contraceptive DRUG

Placebo matching Ethinyl Estradiol / Levonorgestrel tablets

Cohort 5: ABI-H2158 + Oral Contraceptive

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Itraconazole; Rifampin; Midazolam; Ethinyl Estradiol-Norgestrel Combination; Esomeprazole

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Ethinyl Estradiol; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Norgestrel; Norpregnenes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles

Study Officials

• Clinical Study Lead

  Assembly Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 29, 2019
• Study Start: October 18, 2019
• Primary Completion: January 12, 2020
• Study Completion: January 29, 2020
• Last Updated: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)