A Multi-part Study of ALG-000184 to Evaluate Safety, Tolerability, Pharmacokinetics and Drug-drug Interaction Potential After Single and Multiple Doses in Healthy Volunteers

Phase 1Active Not RecruitingNCT06672900

Aligos Therapeutics24 enrolled

Overview

This Phase 1 study consists of two parts, all conducted in healthy volunteers (HVs). In Part 1, the drug-drug interaction (DDI) potential of ALG-000184 will be explored with Itraconazole; participants will be assigned to receive multiple doses of ALG-000184 and Itraconazole over a two week period. In Part 2, the drug-drug interaction (DDI) potential of ALG-000184 will be explored with Carbamazepine; participants will be assigned to receive multiple doses of ALG-000184 and ascending doses of Carbamazepine over an 18 day period. The 2 parts may be conducted in parallel.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Volunteer

Interventions

Carbamazepine

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria for All Participants: 1. Male or female between 18 and 55 years of age. 2. BMI 18.0 to 32.0 kg/m\^2 3. Female participants 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 Participants: 1. Participants 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. Participants 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. Participants with a history of clinically significant drug allergy. 4. Participants with excessive use of alcohol defined as regular consumption of ≥14 standard drinks/week (US CDC 2022) 5. Participants that are unwilling to abstain from alcohol use for 1 week prior to start of the study through end of study follow up. 6. Participants with positive results for urine drug screen, alcohol or cotinine test at screening and Day -1. 7. Participants with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection. 8. Participants with sensitivity to CYP3A4 or P-gp substrates, inhibitors/inducers. 9. Participants with clinically significant abnormal vital signs or physical examination. 10. Participants 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)

Outcomes

Primary Outcomes

Area under the concentration time curve [AUC]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)

Time frame: Up to 24 days

Area under the concentration time curve [AUC]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)

Time frame: Up to 29 days.

Time to maximum plasma concentration [Tmax]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)

Time frame: Up to 29 days

Time to maximum plasma concentration [Tmax]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Itraconazole (Part 1)

Time frame: Up to 24 days

Maximum plasma concentration [Cmax]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)

Time frame: Up to 29 days

Maximum plasma concentration [Cmax]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Itraconazole (Part 1)

Time frame: Up to 24 days

Minimum plasma concentration [Cmin]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)

Time frame: Up to 24 days

Minimum plasma concentration [Cmin]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)

Time frame: Up to 29 days

C0 [predose]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)

Time frame: Up to 24 days

C0 [predose]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)

Time frame: Up to 29 days

Half-life [t1/2]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)

Time frame: Up to 24 days

Half-life [t1/2]

Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)

Time frame: Up to 29 days

Secondary Outcomes

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

The number and severity of treatment emergent adverse events in up to n=24 participants as assessed by DAIDS v2.1(July 2017)

Time frame: Up to 24 days for Part 1

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

The number and severity of treatment emergent adverse events in up to n=24 participants as assessed by DAIDS v2.1(July 2017)

Time frame: Up to 29 days for Part 2

Mean Change from Baseline QTc at different exposure levels

Evaluate the concentration-QT relationship of ALG-000175 and metabolite ALG-000302 to determine the QTc prolongation potential of ALG-000184.

Time frame: Up to 24 days for Part 1.

Mean Change from Baseline QTc at different exposure levels

Evaluate the concentration-QT relationship of ALG-000175 and metabolite ALG-000302 to determine the QTc prolongation potential of ALG-000184.

Time frame: Up to 29 days for Part 2.

A Multi-part Study of ALG-000184 to Evaluate Safety, Tolerability, Pharmacokinetics and Drug-drug Interaction Potential After Single and Multiple Doses in Healthy Volunteers

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes