A First in Human Study to Assess Safety, Tolerability, Pharmacokinetics of ABI-4334 in Healthy Subjects

Study Overview
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Brief Summary
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This study is designed to assess safety, tolerability, and PK of single ascending doses (SAD) of ABI-4334 in Part A and multiple-ascending doses (MAD) of ABI-4334 in Part B in healthy subjects. Effect of food will also be evaluated in Part A.

Official Title
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A Phase 1, Blinded, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics of Single and Multiple Ascending Doses of ABI-4334 in Healthy Subjects

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ABI-4334 Tablet
* Drug: ABI-4334 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) between 18.0 and 30.0 kg/m2 In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results. Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 Agreement to comply with protocol-specified contraceptive requirements Exclusion Criteria: Positive results for any of the following serology tests, HBsAg, hepatitis B core antibody (HBcAb IgM), hepatitis C virus antibody (HCV Ab), or HIV-1 or -2 antibody History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/ distribution/elimination of drugs. History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening Has participated in a clinical study involving administration of either an investigational or a marketed drug within 2 months before Screening

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: SAD Cohorts 1-5 ABI-4334 Tablet<br>A single dose of ABI-4334 will be administered on Day 1 in dose-escalation cohorts with a starting dose of 30 mg. The doses for subsequent cohorts will be determined by evaluation of safety and PK data from previous cohorts. | Drug: ABI-4334 Tablet<br>* ABI-4334 Tablet<br>|
| Placebo Comparator: Part A: SAD Cohorts 1-5 ABI-4334 Placebo Tablet<br>A single dose of placebo matching ABI-4334 will be administered on Day 1. | Drug: ABI-4334 Placebo<br>* Placebo to ABI-4334 Tablet<br>|
| Experimental: Part A: SAD Fed Cohorts 6-7 ABI-4334 Tablet<br>A single dose of ABI-4334 will be administered after a high-fat meal on Day 1 in cohort 6. A single dose of ABI-4334 will be administered on two separate occasions, once fasted and once after a high-fat meal in cohort 7. The dose administered will be determined after evaluation of cumulative safety and PK data from cohorts 1-5. | Drug: ABI-4334 Tablet<br>* ABI-4334 Tablet<br>|
| Placebo Comparator: Part A: SAD Fed Cohorts 6 ABI-4334 Placebo Tablet<br>A single dose of placebo matching ABI-4334 will be administered on Day 1 after a high-fat meal on Day 1 in cohort 6. | Drug: ABI-4334 Placebo<br>* Placebo to ABI-4334 Tablet<br>|
| Experimental: Part B: MAD Cohorts 1-2 ABI-4334 Tablet<br>Once-daily doses of ABI-4334 will be administered from Day 1 to Day 8. Cohort B1 will receive a dose determined from evaluation of the data from the SAD cohorts. The doses for the subsequent cohort will be determined by evaluation of safety and PK data from previous cohorts. | Drug: ABI-4334 Tablet<br>* ABI-4334 Tablet<br>|
| Placebo Comparator: Part B: MAD Cohorts 1-2 ABI-4334 Placebo Tablet<br>Once-daily doses of placebo matching ABI-4334 will be administered from Day 1 to Day 8. | Drug: ABI-4334 Placebo<br>* Placebo to ABI-4334 Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results |  | Up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Maximum Observed Plasma Concentration (Cmax) of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Time to Cmax (Tmax) of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Apparent Terminal Elimination Half Life (t 1/2) of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Comparison of Cmax between fasted and fed treatments of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| SAD Cohorts 1-7: Comparison of AUC between fasted and fed treatments of ABI-4334 |  | before and at pre-specified time points up to 144 hours after dosing | 
| MAD Cohorts 1-2: AUC of ABI-4334 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8 | 
| MAD Cohorts 1-2: Cmax of ABI-4334 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8 | 
| MAD Cohorts 1-2: Tmax of ABI-4334 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8 | 
| MAD Cohorts 1-2: t 1/2 of ABI-4334 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8 | 
| MAD Cohorts 1-2: CL/F of ABI-4334 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8 | 
| MAD Cohorts 1-2: Vz/F of ABI-4334 |  | before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABI-4334, PK, Healthy Subjects