Pharmacokinetics Study of GSK1265744 in Subjects With Severe Renal Impairment

Completed · Phase 1

Conditions studied: Infection, Human Immunodeficiency Virus, HIV Infections

In brief

GSK1265744 (744) is an integrase strand transfer inhibitor (INSTI) currently in development for both the treatment and prevention of human immunodeficiency virus (HIV) infection. Renal elimination of unchanged 744 is extremely low, with no parent 744 detected in the urine after a single 30 mg radiolabeled dose. Despite the minimal contribution of renal clearance on overall 744 elimination, renal impairment may potentially inhibit some pathways of hepatic and gut drug metabolism and transport, and as a result may impact 744 pharmacokinetics. The current Food and Drug Administration (FDA) draft guidance for renal impairment studies suggests that a pharmacokinetic (PK) study in patients with renal impairment be conducted even for those drugs primarily metabolized or secreted in bile. The study will be comprised of two cohorts (severe renal impairment and normal renal function) of 8 subjects each. Upon enrolment, each subject will be admitted to the study center and undergo serial PK sampling following a single dose of oral 744 30 milligrams (mg). Subjects will return to the clinic for follow-up evaluations 10-14 days after the 744 30 mg dose.

Key facts

Study ID

NCT02354937

Run by

ViiV Healthcare

People needed

16

Starts

2015-07-13

Expected to finish

2016-11-01

Last updated by the study team

2020-08-28

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• For Renally Impaired Subjects (Cohort 1)
• Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• Severe renal impairment, defined as individuals with a creatinine clearance of < 30 milliliter (mL)/minute (min) as determined by a 24-hour urine creatinine clearance done at screening.
• Renally impaired subjects must have clinical laboratory test results that are considered clinically stable in the opinion of the principal investigator. Subjects with laboratory parameters outside the reference range may be included if, in the opinion of the investigator and medical monitor, these findings will not interfere with the study or introduce additional safety risk to the subject.
• Body weight >= 50 kilograms (kg) and body mass index (BMI) within the range 19 - 38 kg/ meter (m)\^2 (inclusive)
• Male or female A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum hCG test), not lactating. Women of child-bearing potential must be willing to practice acceptable methods of birth control. Pre-menopausal females defined as 12 months of spontaneous amenorrhea with one of the following: Documented tubal ligation, hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Bilateral Oophorectomy. Postmenopausal
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
• For Healthy Subjects (Cohort 2)
• Healthy control subjects will be matched for age +/-10 years to subjects in the renal impairment cohort but must also remain in the age range:
• Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• Healthy subjects are defined as individuals with a creatinine clearance >= 90 mL/min as determined by a 24-hour urine creatinine clearance done at screening.
• Healthy control subjects will be matched for BMI +/- 25% to subjects in the renal impairment cohort but must also remain in the range of:
• Body weight >=50 kg and BMI within the range 19 - 38 kg/m\^2 (inclusive)
• Male or female A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum hCG test), not lactating. Women of child-bearing potential must be willing to practice acceptable methods of birth control. Pre-menopausal females defined as 12 months of spontaneous amenorrhea with one of the following: Documented tubal ligation, hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Bilateral Oophorectomy. Postmenopausal
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

You may not qualify if…

• For Renally Impaired Subjects (Cohort 1)
• Alanine aminotransferase (ALT) and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Current or chronic history of liver disease (including acute or chronic hepatitis B and C), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Corrected QT Interval (QTc) > 480 millisecond (msec)
• NOTES:
• The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF) machine-read or manually over-read.
• For purposes of data analysis, QT interval corrected for heart rate according to Bazette's formula (QTcB), QTcF, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
• Systolic blood pressure outside the range of 90-160mmHg, or diastolic blood pressure outside the range of 45-95 millimeter of mercury (mmHg), or heart rate outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects in the presence (or absence) of stabilized antihypertensive treatment.
• 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 (not including left or right complete bundle branch block) such as atrioventricular (AV) block [Mobitz type 2 second degree or higher AV block], Wolf Parkinson White [WPW] syndrome or other aberrant pathways.
• Sinus Pauses >3 seconds.
• Any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.
• Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).
• Signs of active infection that in the opinion of the investigator would interfere with the completion of study procedures or the safety of the subject.
• Fluctuating or rapidly deteriorating renal function, or currently receiving hemodialysis, peritoneal dialysis, or any other renal replacement therapy or other medical procedure that serves as a surrogate for renal function. Assessment of the stability of the subject's renal function will be determined by the investigator.
• History of renal transplant.
• History of inflammatory bowel disease.
• History of cholecystectomy or other gastrointestinal surgery (except appendectomy more than three months prior to study).
• History of peptic ulceration or pancreatitis within the preceding 6 months of screening.
• Any other medical condition (except renal 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. This includes but is not limited to any pre-existing condition that interferes with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drug.
• The use of any concurrent prohibited medications
• Subjects with a change in dose regimen of medically required medication within the 2 weeks prior to dosing.
• History of regular alcohol consumption within 6 months of the study defined as:
• An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Inability or unwillingness to comply with lifestyle and/or dietary restrictions

Where it is running

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

Full record on ClinicalTrials.gov

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