Healthy Volunteer
Conditions
Keywords
Healthy Volunteer, ALG-000184
Brief summary
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.
Interventions
DRUGCarbamazepine
Commercially available supply.
Commercially available supply.
DRUGALG-000184
Study Investigational Product
Sponsors
Aligos Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Open-label, fixed sequence, crossover study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration time curve [AUC] | Up to 24 days | Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1) |
| Half-life [t1/2] | Up to 24 days | Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1) |
| C0 [predose] | Up to 24 days | Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1) |
| Minimum plasma concentration [Cmin] | Up to 24 days | Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1) |
| Maximum plasma concentration [Cmax] | Up to 29 days | Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2) |
| Time to maximum plasma concentration [Tmax] | Up to 29 days | Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 24 days for Part 1 | The number and severity of treatment emergent adverse events in up to n=24 participants as assessed by DAIDS v2.1(July 2017) |
| Mean Change from Baseline QTc at different exposure levels | Up to 24 days for Part 1. | Evaluate the concentration-QT relationship of ALG-000175 and metabolite ALG-000302 to determine the QTc prolongation potential of ALG-000184. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration time curve [AUC] | 29 days | Pharmacokinetic parameters of Carbamazepine and applicable metabolite |
| Time to maximum plasma concentration [Tmax] | 24 Days | Pharmacokinetic parameters of Itraconazole and applicable metabolite |
| Half-life [t1/2] | 24 days | Pharmacokinetic parameters of Itraconazole and applicable metabolite |
| C0 [predose] | 24 days | Pharmacokinetic parameters of Itraconazole and applicable metabolite |
| Minimum plasma concentration [Cmin] | 24 days | Pharmacokinetic parameters of Itraconazole and applicable metabolite |
| Maximum plasma concentration [Cmax] | 24 days | Pharmacokinetic parameters of Itraconazole and applicable metabolite |
| Cholesterol | Up to 24 days in Part 1 | Intends to monitor plasma samples from baseline to measure 4-β-hydroxycholesterol, an induction marker of CYP450. |
Countries
United States
Outcome results
None listed