A Study to Assess The Relative Bioavailability of New Tablet Formulations of GSK1265744 in Healthy Adult Subjects
Status: | Completed |
---|---|
Conditions: | HIV / AIDS, HIV / AIDS, HIV / AIDS |
Therapuetic Areas: | Immunology / Infectious Diseases |
Healthy: | No |
Age Range: | 18 - 65 |
Updated: | 5/5/2014 |
Start Date: | February 2014 |
End Date: | June 2014 |
Contact: | US GSK Clinical Trials Call Center |
Email: | GSKClinicalSupportHD@gsk.com |
Phone: | 877-379-3718 |
A Two Part, Single-center, Randomized, Open-label, Crossover Study to Assess The Relative Bioavailability of New Tablet Formulations of GSK1265744 in Healthy Adult Subjects
This study will evaluate two new GSK1265744 sodium salt tablet formulations and provide data
for selection of one of these tablet formulations for use in Phase 3. This is a
single-center, randomized, two part, open-label, crossover study in healthy adult subjects.
Part A is a randomized, open-label, 3-way balanced cross-over design in 24 subjects to
assess the oral bioavailability of two GSK1265744 sodium salt tablet formulations relative
to the current GSK1265744 sodium salt formulation being used in the phase IIb studies under
fasting conditions. Part A treatment periods will be separated by a 14 day washout. After
completion of Part A, preliminary PK data will be analyzed and a decision will be made based
on pre-specified criteria, as to which formulation will be used to conduct Part B. Fifteen
subjects who will have participated in Part A will participate in Part B and receive the
selected formulation with a moderate fat meal. All treatments will be administered as
single 30 mg doses of GSK1265744. Safety evaluations and serial PK samples will be
collected during each treatment period. A follow-up visit will occur 10 - 14 days after the
last dose of study drug.
for selection of one of these tablet formulations for use in Phase 3. This is a
single-center, randomized, two part, open-label, crossover study in healthy adult subjects.
Part A is a randomized, open-label, 3-way balanced cross-over design in 24 subjects to
assess the oral bioavailability of two GSK1265744 sodium salt tablet formulations relative
to the current GSK1265744 sodium salt formulation being used in the phase IIb studies under
fasting conditions. Part A treatment periods will be separated by a 14 day washout. After
completion of Part A, preliminary PK data will be analyzed and a decision will be made based
on pre-specified criteria, as to which formulation will be used to conduct Part B. Fifteen
subjects who will have participated in Part A will participate in Part B and receive the
selected formulation with a moderate fat meal. All treatments will be administered as
single 30 mg doses of GSK1265744. Safety evaluations and serial PK samples will be
collected during each treatment period. A follow-up visit will occur 10 - 14 days after the
last dose of study drug.
Inclusion Criteria:
- Male and females aged between 18 and 65 years of age inclusive, at the time of
signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring.
- Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 18.5-31.0
kg/meter^2 (inclusive).
- A female subject is eligible to participate if she is of: non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy
[for this definition, "documented" refers to the outcome of the
investigator's/designee's review of the subject's medical history for study
eligibility, as obtained via a verbal interview with the subject or from the
subject's medical records]; or postmenopausal defined as 12 months of spontaneous
amenorrhea [in questionable cases a blood sample with simultaneous follicle
stimulating hormone (FSH) > 40 milli-international units per milliliter (MIU/mL) and
estradiol < 40 picogram (pg)/ml (<147 picomole per liter [pmol/L]) is confirmatory];
child-bearing potential with negative pregnancy test as determined by a serum or
urine human chorionic gonadotropin (hCG) test at screening or prior to dosing AND;
agrees to use one of the contraception methods for an appropriate period of time (as
determined by the product label or investigator) prior to the start of dosing to
sufficiently minimize the risk of pregnancy at that point. Female subjects must
agree to use contraception until the final study visit; OR has only same-sex
partners, when this is her preferred and usual lifestyle.
- 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 post-last dose of
study medication.
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5x upper
limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%).
Exclusion Criteria:
- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- 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 of alcohol: 12 ounces (360 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.
- A history of regular use of tobacco- or nicotine-containing products within 6 months
prior to screening.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- The subject's systolic blood pressure is outside the range of 90-140 millimeter of
mercury (mmHg), or diastolic blood pressure is outside the range of 45-90 mmHg.
- History of clinically significant cardiovascular disease including: exclusion
criteria for screening ECG (a single repeat is allowed for eligibility determination)
- Heart rate of <45 and >100 beats per minute for males and <50 and >100 beats per
minute for females; QRS duration >120 milliseconds (msec); QT duration corrected for
heart rate by Bazett's formula (QTc B) >450 milliseconds. Evidence of previous
myocardial infarction (pathologic Q waves, S-T segment changes (except early
repolarization); 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, AV block [2nd degree (type II) or higher], Wolf Parkinson White [WPW]
syndrome); 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. Non-sustained (>=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.
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