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

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

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.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: AL-794; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alios Biopharma Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 3, 2018
• Primary Completion (ACTUAL): April 27, 2018
• Study Completion (ACTUAL): April 27, 2018

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 25, 2018
• First Posted (ACTUAL): January 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2018
• Last Update Submitted That Met QC Criteria: June 4, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: AL-794-806 (OTHER: Alios Biopharma Inc.); 2017-004193-34 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No