An Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK1265744 Administered as a Single Oral Dose and a Study to Describe the Pharmacokinetics of a Supratherapeutic Dose of GSK1265744 in Healthy Adult Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01848340
• Date of registration: 02/05/2013
• Prospective Registration: No
• Primary sponsor: ViiV Healthcare
• Public title: An Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK1265744 Administered as a Single Oral Dose and a Study to Describe the Pharmacokinetics of a Supratherapeutic Dose of GSK1265744 in Healthy Adult Subjects
• Scientific title: An Open Label, Non-Randomized, Mass Balance Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK1265744 Administered as a Single Oral Dose and a Placebo-Controlled, Randomized Study to Describe the Pharmacokinetics of a Supratherapeutic Dose of GSK1265744 in Healthy Adult Subjects
• Date of first enrolment: May 2013
• Target sample size: 16
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01848340
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: ViiV Healthcare

Key inclusion & exclusion criteria

Inclusion Criteria:

- Healthy as determined by a responsible physician, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
monitoring.

- Part A: Male subjects between 30 and 55 years of age at the time of signing the
informed consent.

- Part B: Male or female between 18 and 60 years of age inclusive, at the time of
signing the informed consent.

- Parts A and B male subjects with female partners of child-bearing potential must
agree to use one of the contraception methods listed in protocol. This criterion must
be followed from the time of the first dose of study medication until 14 days after
the last dose of study medication.

- Part B: A female subject is eligible to participate if she is of: Non-childbearing
potential defined as pre-menopausal females with a documented tubal ligation,
bilateral salpingo-oophorectomy or hysterectomy; or postmenopausal defined as 12
months of spontaneous amenorrhea. Woman with child-bearing potential and is abstinent
or agrees to use one of the contraception methods listed in protocol for an
appropriate period of time prior to the start of dosing. Female subjects must agree
to use contraception until 14 days after the last dose of study medication

- Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin <= 1.5xUpper
limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%)

- Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 18.5-31.0
kg/meter square (m^2) (inclusive).

- Capable of giving written informed consent

- Part A only: Available to complete the study (maximum of 21 days confinement in the
clinical research unit).

- Part A only: A history of regular bowel movements (averaging one or more bowel
movements per day).

Exclusion Criteria:

- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome).

- 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.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or
GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.

- Part A only: Subjects who have received a total body radiation dose of greater than
5.0 mSv or exposure to significant radiation (e.g. serial X-ray or computerised
topography (CT) scans, barium meal etc.) in the 12 months prior to this study.

- Part A only: Any condition that could interfere with the accurate assessment and
recovery of radioactivity [14C].

- Part A only: Participation in a clinical trial involving administration of
14C-labelled compound(s) within the last 12 months.

- Part A only: Subjects with a pre-existing condition interfering with normal
gastrointestinal anatomy or motility, hepatic and/or renal function, that could
interfere with the absorption, metabolism, and/or excretion of the study drugs.
Subjects with a history of cholecystectomy must be excluded.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs
that will be screened for include amphetamines, barbiturates, cocaine, opiates,
cannabinoids and benzodiazepines.

- A positive test for human immunodeficiency virus (HIV) antibody.

- Part B only: Pregnant or lactating females as determined by positive serum or urine
Human Chorionic Gonadotropin (hCG) test at screening or prior to dosing.

- The subject's systolic blood pressure is outside the range of 90-140 millimetre of
mercury (mmHg), or diastolic blood pressure is outside the range of 45-90 mmHg.

- History of clinically significant cardiovascular disease including: Heart rate <45
and >100 beats per minute in males and <50 and >100 beats per minute in females. QRS
duration >120 milliseconds (msec) and corrected QT interval (QTc) interval B >450
msec in both males and females. Evidence of previous myocardial infarction,
history/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass
grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or
any clinically significant cardiac disease, any conduction abnormality [including but
not specific to left or right complete bundle branch block, atrioventricular (AV)
block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome) or sinus
pauses >3 seconds.

- Any significant arrhythmia which, in the opinion of the principal Investigator and
GSK Medical Monitor, will interfere with the safety for the individual subject.
Nonsustained (>=3 consecutive ventricular ectopic beats) or sustained ventricular
tachycardia

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer)

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day

- Unable to refrain from the use of prescription or non-prescription drugs, including
vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is
longer) prior to the first dose of study medication, unless in the opinion of the
Investigator and GSK Medical Monitor the medication will not interfere with the study
procedures or compromise subject safety.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Unable to refrain from consumption of red wine, seville oranges, grapefruit or
grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit
juices from 7 days prior to


Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

HIV-associated Lipodystrophy Syndrome

Intervention(s)

Drug: 150 mg GSK1265744B

Drug: GSK1265744B (sodium salt) containing 14C-GSK1265744B

Drug: Placebo

Primary Outcome(s)

Part B: Absolute values and changes over time of hematology as a measure of safety and tolerability. [Time Frame: Up to 14 days]

Part B: Absolute values and changes over time of vital signs as a measure of safety and tolerability. [Time Frame: Up to 14 days]

Part A: Percent recovery of total radioactive [14C] GSK1265744 in urine and feces. [Time Frame: Up to 21 days]

Part B: Number of participants with the use of concurrent medication as a measure of safety and tolerability [Time Frame: Up to 14 days]

Part B: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability. [Time Frame: Up to 14 days]

Part B: Absolute values and changes over time of urinalysis as a measure of safety and tolerability. [Time Frame: Up to 14 days]

Part B: Composite of plasma GSK1265744 PK parameters [Time Frame: Up to 14 days]

Part B: Number of participants with adverse events as a measure of safety and tolerability [Time Frame: Up to 14 days]

Part A: Composite of plasma GSK1265744 PK parameters to access total radioactivity in blood [Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 288, 312 and 336 hours post dose.]

Part B: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability. [Time Frame: Up to 14 days]

Secondary Outcome(s)

Part A: Blood: Plasma ratio of total drug-related material (radioactivity) [Time Frame: Up to 21 days]

Part A: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability. [Time Frame: Up to 21 days]

Part A: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability. [Time Frame: Up to 21 days]

Part A: Absolute values and changes over time of vital signs as a measure of safety and tolerability. [Time Frame: Up to 21 days]

Part A: Absolute values and changes over time of urinalysis as a measure of safety and tolerability. [Time Frame: Up to 21 days]

Part A: Percent of total radioactivity associated with red blood cells [Time Frame: Up to 21 days]

Part A: Absolute values and changes over time of hematology as a measure of safety and tolerability. [Time Frame: Up to 21 days]

Part A: Number of participants with adverse events as a measure of safety and tolerability [Time Frame: Up to 21 days]

Secondary ID(s)

117008

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline