A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults

Study Overview
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Brief Summary
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This study is designed to assess safety, tolerability, pharmacokinetics (PK), formulation (liquid and solid oral forms) and food effect of ABI-H3733 in healthy participants. Part 1 includes evaluation of the safety, tolerability, and PK of ABI-H3733 during single ascending dose (SAD) and multiple-ascending dose (MAD) administration of the oral liquid formulation. Part 2 includes assessment of a solid dosage formulation of ABI-H3733 in participants under fasted conditions or after a high-fat meal. Optional cohorts may be enrolled in Parts 1 and 2 of the study to explore additional dose levels, solid oral dosage formulations, or for cohort expansion.

Official Title
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A Phase 1, Randomized, Blinded, Placebo-Controlled, Single and Multiple Dose Escalation and Food Effect Study of ABI-H3733 in Healthy Subjects

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ABI-H3733 Liquid Oral Dosage Form
* Drug: ABI-H3733 Solid Oral Dosage Form
* Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form
* Drug: Placebo to ABI-H3733 Solid Oral Dosage Form


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No clinically significant abnormal findings on physical exam, medical history, or clinical laboratory results at screening. Exclusion Criteria: Positive test results for human immunodeficiency virus (HIV) or hepatitis B or C. History of or current persistent drug or alcohol abuse.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form<br>A single dose of ABI-H3733 liquid oral dosage form administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts. | Drug: ABI-H3733 Liquid Oral Dosage Form<br>* ABI-H3733 liquid oral dosage form<br>|
| Placebo Comparator: Part 1: SAD Cohorts 1-7 Placebo Liquid Form<br>A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts. | Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form<br>* Placebo to ABI-H3733 liquid oral dosage form<br>|
| Experimental: Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form<br>Once-daily doses of ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts. | Drug: ABI-H3733 Liquid Oral Dosage Form<br>* ABI-H3733 liquid oral dosage form<br>|
| Placebo Comparator: Part 1: MAD Cohorts 8-10 Placebo Liquid Form<br>Once-daily doses of placebo matching ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts. | Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form<br>* Placebo to ABI-H3733 liquid oral dosage form<br>|
| Experimental: Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form<br>A single dose of ABI-H3733 solid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1. | Drug: ABI-H3733 Solid Oral Dosage Form<br>* ABI-H3733 solid oral dosage form<br>|
| Placebo Comparator: Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form<br>A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1. | Drug: Placebo to ABI-H3733 Solid Oral Dosage Form<br>* Placebo to ABI-H3733 solid oral dosage form<br>|
| Experimental: Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form<br>A single dose of ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1. | Drug: ABI-H3733 Solid Oral Dosage Form<br>* ABI-H3733 solid oral dosage form<br>|
| Placebo Comparator: Part 2: Single Dose Fed Cohort 12 Placebo Solid Form<br>A single dose of placebo matching ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1. | Drug: Placebo to ABI-H3733 Solid Oral Dosage Form<br>* Placebo to ABI-H3733 solid oral dosage form<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Adverse Events |  | Up to Day 10 | 
| Number of Participants with One or More Related Adverse Events |  | Up to Day 10 | 
| Number of Participants with One or More Severe (Grade ≥3) Adverse Events |  | Up to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| SAD Cohorts 1-7: Time of Cmax (Tmax) of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| SAD Cohorts 1-7: Apparent Terminal Elimination Half-life (t1/2) of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| MAD Cohorts 8-10: AUC of ABI-H3733 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5 | 
| MAD Cohorts 8-10: Cmax Over the Dosing Interval of ABI-H3733 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5 | 
| MAD Cohorts 8-10: Tmax of ABI-H3733 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5 | 
| MAD Cohorts 8-10: t1/2 of ABI-H3733 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5 | 
| Single Dose Cohorts 11-12: AUC of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| Single Dose Cohorts 11-12: Cmax of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| Single Dose Cohorts 11-12: Tmax of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing | 
| Single Dose Cohorts 11-12: t1/2 of ABI-H3733 |  | before and at pre-specified time points up to 120 hours after dosing |