Overview

Bioavailability Study of a Dolutegravir Dispersible Tablet and Effect of Different Types of Water on the Dispersible Tablet in Healthy Volunteers

Status:
Completed
Trial end date:
2014-09-01
Target enrollment:
0
Participant gender:
All
Summary
Dolutegravir (DTG) is an HIV-1 integrase inhibitor approved in the United States, Canada, Australia and EU. A dispersible tablet has been developed for pediatric use as an alternative to the granule formulation, already in development, and the approved film-coated tablet. This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of five dosing regimens: 20 mg DTG pediatric granules (Treatment A) and of DTG 20 mg dispersible tablets (DTG 20 mg DT) after dispersed in: low mineral content(LMC) water (Treatment B); dispersed in CONTREX™ mineral water (Treatment C); dispersed in low mineral content water and consumed after standing for 30 minutes (Treatment D) and dispersed in CONTREX mineral water and consumed after standing for 30 minutes (Treatment E). Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug. CONTREX is a trademark of Nestlé Waters Corporation.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
ViiV Healthcare
Collaborator:
GlaxoSmithKline
Treatments:
Dolutegravir
Criteria
Inclusion Criteria

- Males or 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. A subject with a clinical abnormality or laboratory parameter(s)
which is/are not specifically listed in the inclusion or exclusion criteria, outside
the reference range for the population being studied may be included only if the
Investigator agree and documents that the finding is unlikely to introduce additional
risk factors and will not interfere with the study procedures.

- Body weight +/- 50 kilogram (kg) for males and +/- 45 kg for females and body mass
index (BMI) within the range 18.5 - 31.0 kilogram/square meter (kg/m^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, bilateral
salpingectomy, bilateral oophorectomy 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 picograms per milliliter (pg/ml) (<147
picomole/liter [pmol/L]) is confirmatory. Child-bearing potential with negative
pregnancy test as determined by serum or urine human chorionic gonadotropin (hCG) test
at screening and 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 5 days post-last dose OR
have only same-sex partners, when this is her preferred and usual lifestyle.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Alanine transaminase (ALT), alkaline phosphatase and bilirubin <= 1.5x upper limit of
the normal range (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%). A single repeat from screening to period 1,
day -1 is allowed for eligibility determination.

- QT duration corrected for heart rate (QTc) < 450 millisecond (msec), using Bazett
Correction Formula, QT correction using Bazett Formula (QTcB). A single repeat from
screening to period 1, day -1 is allowed for eligibility determination.

Exclusion Criteria:

- A positive pre-study drug/alcohol screen.

- A positive test for Human Immunodeficiency Virus (HIV) antibody.

- Pregnant females as determined by positive serum or urine hCG test at screening or
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 mL) of beer, 5 ounces (150 mL)
of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

- 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 GSK
Medical Monitor, contraindicates their participation.

- 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).

- Lactating females.

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

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

- Regular use of tobacco- or nicotine-containing products within 60 days prior to
screening.

- Unable to refrain from the use of prescription or non-prescription drugs, including
vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or
14 days if the drug is a potential enzyme inducer) 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.

- The subject's systolic blood pressure is outside the range of 90-140 millimeters of
mercury (mmHg), or diastolic pressure is outside the range of 45-90 mmHg, or heart
rate is outside the range of 50-100 beats per minute (bpm) for female subjects or
45-110 bpm for male subjects. A single repeat from screening to period 1, day -1 is
allowed for eligibility determination.

- Exclusion criteria for screening electrocardiogram (ECG) (a single repeat is allowed
for eligibility determination): Heart rate - For males <45 and >110 bpm and for
females <50 and >100 bpm, PR Interval <120 and >220 msec, QRS duration <70 and >120
msec, QTc interval (Bazett) >450 msec, evidence of previous myocardial infarction
(Does not include ST segment changes associated with repolarization), any clinically
significant arrhythmia which, in the opinion of the investigator and GSK Medical
Monitor, will interfere with the safety for the individual subject, or any conduction
abnormality with the exception of 1st degree atrioventricular block or incomplete
right bundle branch block