COVID-19
Conditions
Brief summary
This is a Phase 1 non-randomized, open-label, multiple dose, parallel-group study of ALG-097558 in subjects with moderate hepatic impairment and subjects without hepatic impairment, matched for age, body weight and, to the extent possible, for gender. The primary purpose of this study is to characterize the effect of hepatic impairment on the plasma pharmacokinetics of ALG-097558 following administration of multiple, twice daily (Q12H) oral (PO) doses.
Interventions
DRUGALG-097558
Multiple doses of ALG-097558 200 mg (2 x 100 mg tablets)
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Aligos Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is non-randomized, open-label, parallel group study. Cohort 1 will enroll moderately hepatically impaired subjects and Cohort 2 will enroll subjects without hepatic impairment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
for All Subjects: 1. Male and Female between 18 and 75 years old 2. BMI 17.5 to 40.0 kg/m\^2 and a total body weight \>50 kg (110 lb) 3 .Female subjects must either be not of childbearing potential or if they are a woman of childbearing potential, they are only eligible if they and any non-sterile, male sexual partners agree to use highly effective contraceptive therapy 4\. Female subjects must have a negative serum pregnancy test at screening Inclusion Criteria for Subjects with Normal Hepatic Function: 1. Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs and 12-lead electrocardiogram (ECG) assessment 2. Subjects must fit the demographic-matching criteria including body weight, age, and to the extent possible, gender 3. Normal hepatic function with no known or suspected hepatic impairment Inclusion Criteria for Subjects with Impaired Hepatic Function: 1. Subject satisfies the criteria for Class B of the Child-Pugh classification (Child Pugh Scores 7-9 points) within 28 days of study drug administration 2. A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, Fibroscan, computerized tomography scan, or magnetic resonance imaging (MRI) 3. Stable hepatic impairment for at least 3 months prior to screening or second screening visit to demonstrate stability 4. Stable concomitant medications for the management of an individual subject's medical history for at least 28 days prior to screening 5. Subjects must have a 12-lead ECG and vital signs assessment that meet 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. Subjects with a recent (within 1 year of randomization) history or current evidence of drug abuse or recreational drug use 5. Excessive use of alcohol defined as regular consumption of ≥14 units/ week for women and ≥21 units/week for men 6. Unwilling to abstain from alcohol use for 48 hours prior to start of the study through end of study follow up 7. Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection. Subejcts with Hepatitis B infection may be eligible for moderate impairment cohort provided provided they met stable treatment criteria. Subjects with HIV infection may be eligible for moderate impairment cohort provided they met stable treatment criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration [Cmax] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma |
| Area under the concentration time curve [AUC] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma |
| Time to maximum plasma concentration [Tmax] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma |
| Half-life [t1/2] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma |
| Minimum plasma concentration [Cmin] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma |
| C0 [predose] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 20 Days | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 |
Countries
United States
Outcome results
None listed