HIV Infections
Conditions
Keywords
GSK1265744, healthy controls, pharmacokinetic, Hepatic Impairment
Brief summary
This will be a Phase 1, open-label, parallel group, two-part, single-dose adaptive study in adults with moderate and mild (if needed) hepatic impairment and matched, healthy control subjects with normal hepatic function. In Part 1, healthy control subjects (n=8) matched to subjects with moderate (n=8) hepatic impairment will be enrolled. If the geometric mean total plasma area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-infinity\]) of GSK1265744 is increased by \>2-fold in moderately impaired subjects relative to matched controls, Part 2 will be conducted to evaluate GSK1265744 PK in subjects with mild hepatic impairment (n=8) and matched, control subjects (n=8). All subjects will receive a single 30 milligram (mg) oral dose of GSK1265744. The primary objective of the study is to compare plasma PK parameters of GSK1265744 in subjects with hepatic impairment to healthy controls matched in gender, age, and body mass index (BMI).
Interventions
DRUGGSK1265744 30mg
GSK1265744 30mg tablets are white to almost white coated oval tablets. All subjects will receive GSK1265744 30mg as a single oral dose in the fasted state followed by PK sampling.
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Hepatic Impaired Subjects (Cohort 1 and 3) * Between 18 and 70 years of age Part 1 subjects with Moderate Hepatic Impairment Only (Cohort 1): * Subject is considered to have moderate hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. Having moderate hepatic impairment with a Child-Pugh score of 7-9 and previous confirmation of liver cirrhosis. Part 2 subjects with Mild Hepatic Impairment Only (Cohort 3): * Subject is considered to have mild hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. Having mild hepatic impairment, with a Child-Pugh score of 5-6 and previous confirmation of chronic liver disease. * Supplemental inclusion criteria for all hepatically impaired subjects: Chronic (\>6 months), stable (no acute episodes of illness within the previous 1 month prior to screening due to deterioration in hepatic function) hepatic impairment due to any etiology. Subjects must also remain stable throughout the Screening period. - Body weight \>=50 kilogram (kg) and BMI within the range 19 - 41 kilogram per meter square (kg/m\^2) (inclusive). * Male or female: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and the protocol. Inclusion Criteria for Healthy Subjects (Cohorts 2 and 4): * Healthy control subjects will be matched for age +/-10 years to subjects in the respective hepatic impairment cohort but must also remain in the age range between 18 and 70 years inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee. Healthy control subjects will be matched for BMI +/-25 percent to subjects in the respective hepatic impairment cohort but must also remain in the range of: Body weight \>=50 kg and BMI within the range 19 - 41 kg/m\^2 (inclusive) * Male or female: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)] following a single oral dose of GSK1265744 | Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8) | Plasma PK samples (2 mL of blood per sample) will be collected to measure GSK1265744 at the following time points: pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose |
| Maximum observed concentration (Cmax) following a single oral dose of GSK1265744 | Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8) | Plasma PK samples (2 mL of blood per sample) will be collected to measure GSK1265744 at the following time points: pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) assessment | Up to Day 14 | An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product |
| Composite of Clinical laboratory parameters including hematology, and clinical chemistry | Up to Day 14 | Assessment of Laboratory parameters will include hematology, and clinical chemistry |
| Unbound concentration and unbound fraction in plasma of GSK1265744 at 2 and 24 hours post dose | Up to 24 hours post dose (Day 2) | Blood samples will be collected to measure bound and unbound plasma GSK1265744 concentrations at 2 and 24 hours post dose |
| Composite of Vital signs assessments will include measurement of temperature, systolic and diastolic blood pressure, heart rate and respiratory rate | Up to Day 14 | Vital signs will be measured in semi-supine position after 10 minutes rest and will include temperature, systolic and diastolic blood pressure (BP), heart rate (HR) and respiratory rate |
| Electrocardiogram (ECG) monitoring | Up to Day 2 | 12-lead ECGs will be performed with the subject in a semi-supine position having rested in this position for at least 10 minutes beforehand |
| Composite of PK parameters including AUC(0-t), %AUCex, C24, t1/2, CL/F, tlag, tmax, and Vz/F following a single oral dose of GSK1265744 | Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8) | PK parameters including plasma area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration \[AUC(0-t)\], percentage of AUC(0-infinity) obtained by extrapolation (%AUCex), concentration observed at 24-hours post dose (C24), apparent terminal phase half-life (t1/2), apparent clearance (CL/F), lag time before observation of drug concentrations (tlag), time of occurrence of Cmax (tmax) and apparent terminal phase volume of distribution (Vz/F) following a single oral dose of GSK1265744 |
Countries
United States
Outcome results
None listed