A Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeated Dosing Regimens of AL-794 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability (including incidence of central nervous system [CNS] related events such as lightheadedness and dizziness), of multiple oral doses of AL-794 in healthy volunteers (HV). Also, to evaluate the pharmacokinetics of ALS-033719 and ALS-033927 in plasma after multiple oral doses of AL-794 in HV.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeated Dosing Regimens of AL-794 in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: AL-794
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has provided written informed consent In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions and is likely to complete the study as planned Participant is deemed healthy on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening Body mass index (BMI) 18 - 32 kilogram per meter square (kg/m^2), inclusive. The minimum weight is 50 kilogram (kg). No more than 25 percent (%) of participants may be enrolled with a BMI greater than or equal to (>=) 30 kg/m^2 Female participants must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening and on Day -1 (admission) Exclusion Criteria: Female who is pregnant as confirmed by a positive beta-human chorionic gonadotropin (beta-hCG) laboratory test, or who was pregnant within 6 months prior to study start, or who is breast-feeding, or who is planning to become pregnant from signing of the informed consent form (ICF) until 90 days after the last dose of study drug Male whose female partner is pregnant or contemplating pregnancy from the date of screening until 90 days after their last dose of study drug Participant with one or more of the following laboratory abnormalities at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 1.2*upper limit of normal (ULN); Alkaline phosphatase (ALP) >= 1.2*ULN; Total bilirubin >= 1.2*ULN; Clinically significant laboratory abnormalities or abnormalities which are deemed to interfere with the ability to interpret study data Creatinine clearance less than (<) 90 milliliter per minute (mL/min) (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) Positive screening test for human immunodeficiency virus type 1 (HIV-1) or HIV-2 antibody, or for current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]), or hepatitis B virus (HBV) infection (confirmed by hepatitis B surface antigen [HBsAg]), or hepatitis C virus (HCV) infection (confirmed by HCV antibody) at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (AL-794 or Placebo)<br>Participants will receive AL-794 or placebo in 2:1 ratio in Cohorts 1 to 3. AL-794 will be administered at a 100 milligram (mg) loading dose (LD) on the morning of Day 1, followed by a 50 mg maintenance dose (MD) on the evening of Day 1 and twice-daily (BID) on Day 2 through Day 5. The duration of dosing may be extended (maximum duration 10 days), at the discretion of the Sponsor and Principal Investigator (PI). | Drug: AL-794<br>* AL-794 will be administered as tablets orally on Day 1 to Day 5.<br>Drug: Placebo<br>* Matching placebo tablets will be administered.<br>|
| Experimental: Part 2 (AL-794 or Placebo)<br>Participants will receive AL-794 or placebo in 2:1 ratio. AL-794 will be administered as 100 mg LD on the morning of Day 1, followed by a 50 mg MD on the evening of Day 1 and BID on Day 2 through Day 5. The duration of dosing may be extended (maximum duration 10 days). Based on the results of Part 1, the duration of dosing may be modified. | Drug: AL-794<br>* AL-794 will be administered as tablets orally on Day 1 to Day 5.<br>Drug: Placebo<br>* Matching placebo tablets will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical occurrence in a participant who received study drug or placebo without regard to possibility of causal relationship. | Up to 40 days | 
| Part 1: ALS-033719 Plasma Concentrations | Plasma concentration assessment will be done for ALS-033719 following multiple doses of AL-794. | Predose up to Day 12 | 
| Part 2: ALS-033719 Plasma Concentrations | Plasma concentration assessment will be done for ALS-033719 following multiple doses of AL-794. | Predose up to Day 5 | 
| Part 1: ALS-033927 Plasma Concentrations | Plasma concentration assessment will be done for ALS-033927 following multiple doses of AL-794. | Predose up to Day 12 | 
| Part 2: ALS-033927 Plasma Concentrations | Plasma concentration assessment will be done for ALS-033927 following multiple doses of AL-794. | Predose up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: ALS-033719 Plasma Concentrations in Healthy Women in Fasted and Fed Conditions | Plasma concentration assessment will be done for ALS-033719, after repeated oral doses of AL-794, in healthy women under fasted and fed conditions. | Predose up to Day 12 | 
| Part 1: ALS-033927 Plasma Concentrations in Healthy Women in Fasted and Fed Conditions | Plasma concentration assessment will be done for ALS-033927, after repeated oral doses of AL-794, in healthy women under fasted and fed conditions. | Predose up to Day 12 | 
| Part 1 and Part 2: Time-Matched Q-T Interval Corrected for Heart Rate Using Fridericia Method (QTcF) | The QTcF will be measured by electrocardiogram (ECG). | Up to 40 days |