A Study to Evaluate Pharmacokinetic (PK) and Safety of GSK1265744 in Subjects With Hepatic Impairment and Control Healthy Volunteers

Completed · Phase 1

Conditions studied: HIV Infections

In brief

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).

Key facts

Study ID

NCT02354950

Run by

ViiV Healthcare

People needed

16

Starts

2015-06-22

Expected to finish

2016-09-16

Last updated by the study team

2020-08-05

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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.

You may not qualify if…

• Exclusion Criteria for Hepatic Impaired Subjects (Cohort 1 and 3):
• Presence of Grade 3 or 4 elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin; corrected QT interval (QTc) > 480 milliseconds (msec);
• The subject's systolic BP is outside the range of 90-160 millimeter of mercury (mmHg), or diastolic BP is outside the range of 45-95mmHg or heart rate is outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects
• Evidence of previous myocardial infarction in the past 12 months or any clinically significant active cardiovascular disease that, in the opinion of the investigator, could interfere with the safety of the subject.
• Any clinically significant conduction abnormality
• Any significant arrhythmia.
• Non-sustained or sustained ventricular tachycardia.
• Evidence of recent infection with Hepatitis B and/or Hepatitis C within preceding 6 months. Subjects with chronic Hepatitis B or C (duration>6 months)
• Subjects with a pre-existing condition (except hepatic impairment) interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy and inflammatory bowel disease should be excluded.
• Subjects with a history of peptic ulceration or pancreatitis within the preceding 6 months of screening should be excluded.
• Subjects with previous gastrointestinal (GI) surgery (except appendectomy more than three months prior to study) should be excluded.
• Subjects with creatinine clearance (CLCR) <=60 milliliter per minute (mL/min) (calculated by the Modification of Diet in Renal Disease [MDRD] equation).
• Subjects with advanced ascites (Grade 3 or 4).
• Subjects with refractory encephalopathy as judged by the investigator or significant Central Nervous System (CNS) disease.
• History of gastric or esophageal variceal bleeding within the past 6 months;
• Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement;
• Presence of hepatopulmonary or hepatorenal syndrome;
• Presence of primarily cholestatic liver diseases;
• History of liver transplantation;
• Subjects with signs of active infection;
• Subjects with unstable cardiac function or subjects with hypertension whose blood pressure is not controlled;
• Diabetic subjects whose diabetes is not controlled;
• Subjects with any other medical condition (other than hepatic impairment) which, in the judgment of the investigator and medical monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject;
• Subjects requiring any concurrent prohibited medication listed in study protocol;
• Subjects receiving lactulose who are medically unable to halt lactulose administration from 8 hours before dosing with study drug to 4 hours after dosing with study drug;

Where it is running

• GSK Investigational Site — Lakewood, Colorado, United States
• GSK Investigational Site — Orlando, Florida, United States
• GSK Investigational Site — Minneapolis, Minnesota, United States

Full record on ClinicalTrials.gov

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