Overview

Relative Bioavailability Study of Two New Dolutegravir/Abacavir/Lamivudine Fixed Dose Combination Tablets

Status:
Completed
Trial end date:
2011-07-01
Target enrollment:
0
Participant gender:
All
Summary
Dolutegravir (DTG, GSK1349572) is a next-generation integrase inhibitor (INI) currently in phase 3 clinical trials for human immunodeficiency virus (HIV). Fixed-dose combinations (FDCs) have greatly simplified the treatment of patients with HIV. While Atripla (an FDC of tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) has become the preferred first line regimen due in large part to its convenient presentation as a full treatment regimen in a single product, other options are needed. A fixed-dose combination of DTG/abacavir (ABC)/lamivudine (3TC) is one such opportunity. This is a single-center, randomized, open-label, 3-period crossover study in healthy adult subjects to evaluate the single-dose relative bioavailability of two experimental oral DTG 50 mg/ABC 600 mg/3TC 300 mg FDC tablet formulations compared to co-administration of the separate tablet formulations (DTG 50 mg tablet and EPZICOM), with each dose administered in the fasted state. Approximately 18 subjects will be enrolled and randomized to one of 6 different treatment sequences. There will be a screening visit within 30 days prior to the first dose of study drug and a follow up visit within 7-14 days after the last dose. There will be a 7 day washout between doses in each treatment period. The following PK parameters for DTG, ABC and 3TC will be measured: area under the concentration curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), Area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration (AUC (0-t)), maximum observed concentration (Cmax), lag time before observation of drug concentrations (tlag), time of occurrence of Cmax (tmax), terminal phase half-life (t½), apparent clearance following oral dosing (CL/F) and apparent terminal phase volume of distribution (Vz/F).
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
ViiV Healthcare
Collaborators:
GlaxoSmithKline
Shionogi
Treatments:
Abacavir
Dideoxynucleosides
Dolutegravir
Integrase Inhibitors
Lamivudine
Reverse Transcriptase Inhibitors
Criteria
Inclusion Criteria:

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

- Male or female between 18 and 65 years of age inclusive, at the time of signing the
informed consent.

- A female subject is eligible to participate if she is of: Non-childbearing potential
or child-bearing potential and agrees to use one of the contraception methods listed
in the protocol until the follow-up visit.

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods listed in the protocol until 84 days after the last dose of
study drug.

- Body weight greater than 50 kg for males and greater than 45 kg for females and BMI
within the range 18.5- 31.0 kg/m2 (inclusive).

- ALT, alkaline phosphatase and bilirubin less than 1.5xULN (isolated bilirubin >1.5xULN
is acceptable if bilirubin is fractionated and direct bilirubin <35%).

- A negative HLA-B*5701 allele screening assessment

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

Exclusion Criteria:

- 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.

- 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).

- 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.

- 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.

- If heparin is used during PK sampling, subjects with a history of sensitivity to
heparin or heparin-induced thrombocytopenia should not be enrolled.

- History of regular alcohol consumption within 6 months of the study defined as:An
average weekly intake of >14 drinks/week for men or >7 drinks/week for women. 7.
Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days
prior to the first dose of study medication.

- Pregnant females as determined by positive serum or urine human chorionic
gonadotrophin (hCG) test at screening or prior to dosing.

- Lactating females.

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

- 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, peptic ulceration, inflammatory bowel disease or pancreatitis
should be excluded.

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

- A positive test for HIV antibody.

- History of Gilbert's disease.

- 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's systolic blood pressure is outside the range of 90-140mmHg, or diastolic
blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of
50-100bpm for female subjects or 45-100 bpm for male subjects.

- Exclusion criteria for screening ECG outside of protocol limits.