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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / 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: Itraconazole; Itraconazole capsules; Drug: ABI-H2158; ABI-H2158 tablets
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: Esomeprazole; Esomeprazole capsules; Drug: ABI-H2158; ABI-H2158 tablets
Experimental: Cohort 4: ABI-H2158 + Midazolam; Oral midazolam on Days 1 and 11; oral ABI-H2158 QD on Days 2 through 11	Drug: Midazolam; Midazolam syrup; Drug: ABI-H2158; ABI-H2158 tablets
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Study Director: Clinical Study Lead, Assembly Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2019
• Primary Completion (Actual): January 12, 2020
• Study Completion (Actual): January 29, 2020

Study Registration Dates

• First Submitted: October 16, 2019
• First Submitted That Met QC Criteria: October 26, 2019
• First Posted (Actual): October 29, 2019

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Anti-Bacterial Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptive Agents, Female; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP3A Inducers; Contraceptives, Oral, Synthetic; Antitubercular Agents; Contraceptives, Oral, Hormonal; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Midazolam; Levonorgestrel; Estradiol; Contraceptive Agents; Ethinyl Estradiol; Contraceptives, Oral; Rifampin; Itraconazole; Esomeprazole; Ethinyl estradiol, levonorgestrel drug combination
• Other Study ID Numbers: ABI-H2158-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No