A Study of AL-034 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses in Healthy Participants
- Registration Number
- NCT03285620
- Lead Sponsor
- Alios Biopharma Inc.
- Brief Summary
This is a Phase 1 first-in-human (FIH) study evaluating single and multiple dose administration of AL-034 in healthy adult participants. The aim is to examine the safety (including pharmacodynamic \[PD\] biomarker assessments), tolerability, and pharmacokinetics (PK) of increasing single ascending doses (SADs) (Part 1) and multiple ascending doses (MADs) (Part 2) of AL-034. The potential food effect will be investigated in healthy adult participants at one or optionally 2 single dose level(s).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Single Ascending Dose (SAD) Placebo Participants will receive single oral dose of AL-034 (oral solution) (the starting dose in Cohort 1 of Part 1 will be 0.2 milligram \[mg\]) or matching placebo under fasted condition (Cohorts 1 to 5 or optional Cohort 7) on Day 1. Participants may receive AL-034 in a fed state (Cohort 6) to evaluate the effect of food on the pharmacokinetics (PK) of AL-034. Part 2: Multiple-Dose Administration (MAD) Placebo Participants will receive multiple oral doses of AL-034 or matching placebo for 4 consecutive weeks either once weekly (Qwk - for 4 doses) or every two weeks (Q2wk - for 3 doses) under fed or fasted conditions. The starting dose for Part 2 will be determined based on the initial PK and safety/tolerability data from Part 1. Part 1: Single Ascending Dose (SAD) AL-034 Participants will receive single oral dose of AL-034 (oral solution) (the starting dose in Cohort 1 of Part 1 will be 0.2 milligram \[mg\]) or matching placebo under fasted condition (Cohorts 1 to 5 or optional Cohort 7) on Day 1. Participants may receive AL-034 in a fed state (Cohort 6) to evaluate the effect of food on the pharmacokinetics (PK) of AL-034. Part 2: Multiple-Dose Administration (MAD) AL-034 Participants will receive multiple oral doses of AL-034 or matching placebo for 4 consecutive weeks either once weekly (Qwk - for 4 doses) or every two weeks (Q2wk - for 3 doses) under fed or fasted conditions. The starting dose for Part 2 will be determined based on the initial PK and safety/tolerability data from Part 1.
- Primary Outcome Measures
Name Time Method Part 2: Number of Participants With AEs by Severity Approximately up to 12 weeks Severity of AEs will be graded according to the Division of AIDS (DAIDS) Toxicity Grading Scale as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening); and Grade 5 (death related to the AE).
Part 1: Number of Participants with Holter Monitoring Abnormalities Approximately up to 9 weeks Number of participants with Holter monitoring abnormalities (related to heart's activity such as rate and rhythm) will be reported.
Part 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Approximately up to 9 weeks An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Part 1: Number of Participants With AEs by Severity Approximately up to 9 weeks Severity of AEs will be graded according to the Division of Acquired Immune Deficiency Syndrome (DAIDS) Toxicity Grading Scale as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening); and Grade 5 (death related to the AE).
Part 2: Number of Participants with Vital Sign Abnormalities Approximately up to 12 weeks Number of participants with vital signs abnormalities (vital signs includes body temperature, pulse rate, respiratory rate, oxygen saturation \[SaO2\] and blood pressure) will be reported.
Part 2: Number of Participants with Laboratory Abnormalities Approximately up to 12 weeks Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported.
Part 1: Number of Participants with Electrocardiogram (ECG) Abnormalities Approximately up to 9 weeks Number of participants with electrocardiogram (ECG) abnormalities will be reported.
Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities Approximately up to 12 weeks Number of participants with electrocardiogram (ECG) abnormalities will be reported.
Part 1: Number of Participants with Vital Sign Abnormalities Approximately up to 9 weeks Number of participants with vital signs abnormalities (vital signs includes body temperature, pulse rate, respiratory rate, oxygen saturation \[SaO2\] and blood pressure) will be reported.
Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Approximately up to 12 weeks An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Part 1: Number of Participants with Clinically Significant Changes in Physical Examination Approximately up to 9 weeks Number of participants with clinically significant changes in the physical examination (including height, body weight measurement, and skin examination) will be reported.
Part 1: Number of Participants with Cytokine Release Syndrome (CRS) by Severity Approximately up to 9 weeks Severity of CRS will be graded according to DAIDS as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); and Grade 4 (potentially life-threatening).
Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Repeated Dose Administration Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose AUC is the area under the plasma concentration time curve of AL-034 in plasma following MAD administration.
Part 2: Number of Participants with Clinically Significant Changes in Physical Examination Approximately up to 12 weeks Number of participants with clinically significant changes in the physical examination (including height, body weight measurement, and skin examination) will be reported.
Part 2: Number of Participants with Holter Monitoring Abnormalities Approximately up to 12 weeks Number of participants with Holter monitoring abnormalities (related to heart's activity such as rate and rhythm) will be reported.
Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fasted State Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose The Cmax is the maximum observed concentration of AL-034 in plasma following single ascending dose (SAD) administration.
Part 1: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fasted State Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose AUC is the area under the plasma concentration time curve of AL-034 in plasma following SAD administration.
Part 1: AL-034 Concentration in Urine Following a Single Dose Administration Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose Concentration in urine of AL-034 following a single dose administration will be determined.
Part 1: Number of Participants with Laboratory Abnormalities Approximately up to 9 weeks Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported.
Part 1: Number of Participants with Cytokine Release Syndrome (CRS) Approximately up to 9 weeks Number of participants with CRS will be reported. CRS is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.
Part 2: Number of Participants with Cytokine Release Syndrome (CRS) Approximately up to 12 weeks Number of participants with CRS will be reported. CRS is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.
Part 2: Number of Participants with Cytokine Release Syndrome (CRS) by Severity Approximately up to 12 weeks Severity of CRS will be graded according to DAIDS as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); and Grade 4 (potentially life-threatening).
Part 2: AL-034 Concentration in Urine Following Repeated Dose Administration Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose Concentration in urine of AL-034 following MAD administration will be determined.
Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Repeated Dose Administration Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose The Cmax is the maximum observed concentration of AL-034 in plasma following multiple ascending dose (MAD) administration.
- Secondary Outcome Measures
Name Time Method Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fed State Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose The Cmax is the maximum observed concentration of AL-034 in plasma following SAD administration.
Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fed State Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose AUC is the area under the plasma concentration time curve of AL-034 in plasma following SAD administration.
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Trial Locations
- Locations (1)
Auckland Clinical Studies, Ltd.
🇳🇿Auckland, New Zealand