A First-in-Human Multi-Part Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558

Aligos Therapeutics90 enrolled

Overview

A multi-part study of ALG-097558 to evaluate safety, tolerability, pharmacokinetics and drug-drug interaction potential after single and multiple doses in healthy volunteers

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

COVID-19

Interventions

ALG-097558DRUG

single or multiple doses of ALG-097558

PlaceboDRUG

single or multiple doses of placebo

MidazolamDRUG

Multiple doses of Midazolam

Itraconazole

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria for All Subjects: 1. Male and Female between 18 and 55 years old 2. BMI 18.0 to 32.0 kg/m\^2 3. Female subjects must have a negative serum pregnancy test at screening 4. Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria Exclusion Criteria for All Subjects: 1. Subjects with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation 2. Subjects with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT Syndrome) or history or clinical evidence at screening of significant or unstable cardiac disease etc. 3. Subjects with a history of clinically significant drug allergy 4. Excessive use of alcohol defined as regular consumption of ≥14 units/week 5. Unwilling to abstain from alcohol use for 1 week prior to start of the study through end of study follow up 6. Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection 7. Subjects with renal dysfunction (e.g., estimated creatinine clearance \<90 mL/min/1.73 m\^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula)

Locations (1)

Hammersmith Medicines Research

London, United Kingdom

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Time frame: Up to 11 days for Part 1

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Time frame: Up to 20 days for Part 2

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Time frame: Up to 20 days for Part 3

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Time frame: Up to 23 days for Part 4

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Time frame: Up to 28 days for Part 5

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Time frame: Up to 17 days for Part 6

Area under the concentration time curve [AUC]

Pharmacokinetic parameters of Midazolam and applicable metabolites

Time frame: Predose (-2 hours) up to 11 days

Time to maximum plasma concentration [Tmax]

Data from ClinicalTrials.gov

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Multiple doses of Itraconazole

CarbamazepineDRUG

Multiple doses of Carbamazepine

ALG-097558 in solution formulationDRUG

ALG-097558 in solution administered in fasted state

ALG-097558 in tablet formulationDRUG

ALG-097558 in tablet administered in fasted and fed state

Pharmacokinetic parameters of Midazolam and applicable metabolites

Time frame: Predose (-2 hours) up to 11 days

Maximum plasma concentration [Cmax]

Pharmacokinetic parameters of Midazolam and applicable metabolites

Time frame: Predose (-2 hours) up to 11 days

Minimum plasma concentration [Cmin]

Pharmacokinetic parameters of Midazolam and applicable metabolites

Time frame: Predose (-2 hours) up to 11 days

C0 [predose]

Pharmacokinetic parameters of Midazolam and applicable metabolites

Time frame: Predose (-2 hours) up to 11 days

Half-life [t1/2]

Pharmacokinetic parameters of Midazolam and applicable metabolites

Time frame: Predose (-2 hours) up to 11 days

Area under the concentration time curve [AUC]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine

Time frame: Predose (-0.75 hours) up to 19 days

Time to maximum plasma concentration [Tmax]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine

Time frame: Predose (-0.75 hours) up to 19 days

Maximum plasma concentration [Cmax]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine

Time frame: Predose (-0.75 hours) up to 19 days

Minimum plasma concentration [Cmin]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine

Time frame: Predose (-0.75 hours) up to 19 days

C0 [predose]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine

Time frame: Predose (-0.75 hours) up to 19 days

Half-life [t1/2]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine

Time frame: Predose (-0.75 hours) up to 19 days

Area under the concentration time curve [AUC]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet

Time frame: Predose (-0.75 hours) up to 9 days

Time to maximum plasma concentration [Tmax]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet

Time frame: Predose (-0.75 hours) up to 9 days

Maximum plasma concentration [Cmax]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet

Time frame: Predose (-0.75 hours) up to 9 days

Minimum plasma concentration [Cmin]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet

Time frame: Predose (-0.75 hours) up to 9 days

C0 [predose]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet

Time frame: Predose (-0.75 hours) up to 9 days

Half-life [t1/2]

Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet

Time frame: Predose (-0.75 hours) up to 9 days

Secondary Outcomes

Maximum plasma concentration [Cmax]

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days

Area under the concentration time curve [AUC]

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days

Time to maximum plasma concentration [Tmax]

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days

Minimum plasma concentration [Cmin]

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days

Half-life [t1/2]

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days

C0 [predose]

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days

Dose Proportionality

Pharmacokinetic parameters of ALG-097558 in plasma

Time frame: Predose (-0.75 hours) up to 19 days