A Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeated Dosing Regimens of AL-794 in Healthy Volunteers
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 (AL-794 or Placebo) 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
AL-794 will be administered as tablets orally on Day 1 to Day 5.
Drug: Placebo
Matching placebo tablets will be administered.
|
| Experimental: Part 2 (AL-794 or Placebo) 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
AL-794 will be administered as tablets orally on Day 1 to Day 5.
Drug: Placebo
Matching placebo tablets will be administered.
|
Outcome Measures
Primary Outcome Measures
- Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [Up to 40 days]
An AE is any untoward medical occurrence in a participant who received study drug or placebo without regard to possibility of causal relationship.
- Part 1: ALS-033719 Plasma Concentrations [Predose up to Day 12]
Plasma concentration assessment will be done for ALS-033719 following multiple doses of AL-794.
- Part 2: ALS-033719 Plasma Concentrations [Predose up to Day 5]
Plasma concentration assessment will be done for ALS-033719 following multiple doses of AL-794.
- Part 1: ALS-033927 Plasma Concentrations [Predose up to Day 12]
Plasma concentration assessment will be done for ALS-033927 following multiple doses of AL-794.
- Part 2: ALS-033927 Plasma Concentrations [Predose up to Day 5]
Plasma concentration assessment will be done for ALS-033927 following multiple doses of AL-794.
Secondary Outcome Measures
- Part 1: ALS-033719 Plasma Concentrations in Healthy Women in Fasted and Fed Conditions [Predose up to Day 12]
Plasma concentration assessment will be done for ALS-033719, after repeated oral doses of AL-794, in healthy women under fasted and fed conditions.
- Part 1: ALS-033927 Plasma Concentrations in Healthy Women in Fasted and Fed Conditions [Predose up to Day 12]
Plasma concentration assessment will be done for ALS-033927, after repeated oral doses of AL-794, in healthy women under fasted and fed conditions.
- Part 1 and Part 2: Time-Matched Q-T Interval Corrected for Heart Rate Using Fridericia Method (QTcF) [Up to 40 days]
The QTcF will be measured by electrocardiogram (ECG).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant has provided written informed consent
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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
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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
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Body mass index (BMI) 18 - 32 kilogram per meter square (kg/m2), 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/m2
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Female participants must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening and on Day -1 (admission)
Exclusion Criteria:
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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
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Male whose female partner is pregnant or contemplating pregnancy from the date of screening until 90 days after their last dose of study drug
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Participant with one or more of the following laboratory abnormalities at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 1.2upper limit of normal (ULN); Alkaline phosphatase (ALP) >= 1.2ULN; Total bilirubin >= 1.2*ULN; Clinically significant laboratory abnormalities or abnormalities which are deemed to interfere with the ability to interpret study data
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Creatinine clearance less than (<) 90 milliliter per minute (mL/min) (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation)
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hammersmith Medicines Research | London | United Kingdom | NW10 7EW |
Sponsors and Collaborators
- Alios Biopharma Inc.
Investigators
- Principal Investigator: Adeep Puri, MD, Hammersmith Medicines Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AL-794-806
- AL-794-806
- 2017-004193-34