A Phase 1, Randomized, Blinded, Placebo-Controlled, Single and Multiple Dose Escalation and Food Effect Study of ABI-H3733 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- ABI-H3733 Liquid Oral Dosage Form
- Conditions
- Chronic Hepatitis B
- Sponsor
- Assembly Biosciences
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Number of Participants with One or More Adverse Events
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form
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.
Intervention: ABI-H3733 Liquid Oral Dosage Form
Part 1: SAD Cohorts 1-7 Placebo Liquid Form
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.
Intervention: Placebo to ABI-H3733 Liquid Oral Dosage Form
Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form
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.
Intervention: ABI-H3733 Liquid Oral Dosage Form
Part 1: MAD Cohorts 8-10 Placebo Liquid Form
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.
Intervention: Placebo to ABI-H3733 Liquid Oral Dosage Form
Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form
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.
Intervention: ABI-H3733 Solid Oral Dosage Form
Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form
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.
Intervention: Placebo to ABI-H3733 Solid Oral Dosage Form
Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form
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.
Intervention: ABI-H3733 Solid Oral Dosage Form
Part 2: Single Dose Fed Cohort 12 Placebo Solid Form
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.
Intervention: Placebo to ABI-H3733 Solid Oral Dosage Form
Outcomes
Primary Outcomes
Number of Participants with One or More Adverse Events
Time Frame: Up to Day 10
Number of Participants with One or More Related Adverse Events
Time Frame: Up to Day 10
Number of Participants with One or More Severe (Grade ≥3) Adverse Events
Time Frame: Up to Day 10
Secondary Outcomes
- 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)
- SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- 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)
- 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)
- 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)