Overview

Bioequivalence Study of a Fixed-dose Combination (FDC) of Dolutegravir (DTG) and Rilpivirine (RPV)

Status:
Completed
Trial end date:
2016-10-24
Target enrollment:
0
Participant gender:
All
Summary
The purpose of the study is to evaluate the bioequivalence between Fixed-dose Combination (FDC) tablet formulation of Dolutegravir (DTG) 50 milligrams (mg) and Rilpivirine (RPV) 25 mg versus co-administration of the separate tablet formulations of DTG 50 mg plus RPV 25 mg, in the fed state. This pivotal bioequivalence study, is to serve as a pharmacokinetic (PK) bridge to the ongoing Phase 3 trials with the separate agents. This study will be conducted under fed conditions to appropriately mimic the conditions in the Phase 3 trials. This is a single-center, randomized, open-label, 2-period, single-dose, crossover study. A minimum of 86 healthy adult subjects will be randomized such that a minimum of approximately 82 evaluable subjects complete the study. The total duration of participation of a subject in this study will be approximately 8 weeks which includes a screening visit within 30 days prior to the first dose of study drug, two treatment periods each with a single dose of study drug and a follow-up visit within 12-17 days after the last dose of study drug. There will be a washout of at least 21 days between each dose of study drug. A blinded (for treatment) review of DTG and RPV plasma concentration data for approximately the first 40 subjects will be conducted. If the within-subject coefficients of variation (CVw%) for either DTG or RPV maximal drug concentration (Cmax) values are >=31%; a sample size re-estimation will be employed and additional subjects (beyond the 86 planned) will be randomized for treatment in the study. Following the re-estimation, it is possible that up to approximately 154 healthy adult subjects (68 new subjects in addition to the planned 86 subjects above) will be randomized such that a maximum of approximately 146 evaluable subjects could complete the study.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
ViiV Healthcare
Collaborator:
GlaxoSmithKline
Treatments:
Dolutegravir
Rilpivirine
Criteria
Inclusion Criteria:

- Age: Between 18 and 55 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 evaluation (history, ECG).

- 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 in
consultation with the Medical Monitor if required agree and document that the finding
is unlikely to introduce additional risk factors and will not interfere with the study
procedures.

- Body weight >=50 kilograms (kg) (110 pounds [lbs]) for men and >=45 kg (99 lbs) for
women and body mass index (BMI) within the range 18.5-31.0 kg/square meter (m^2)
(inclusive)

- Male or Female.

Females: A female subject is eligible to participate if she is not pregnant (as confirmed
by a negative [serum or urine according to site standard procedure] human chorionic
gonadotrophin [hCG] test), not lactating, and at least one of the following conditions
applies:

- Non-reproductive potential defined as: Pre-menopausal females with one of the
following: Documented tubal ligation; Documented hysteroscopic tubal occlusion
procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy;
Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous
amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status
is in doubt will be required to use one of the highly effective contraception methods
if they wish to continue their HRT during the study. Otherwise, they must discontinue
HRT to allow confirmation of post-menopausal status prior to study enrollment.

- Reproductive potential and agrees to follow one of the options listed in the Modified
List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
Potential (FRP) from 30 days prior to the first dose of study medication and until (at
least five terminal half-lives OR until any continuing pharmacologic effect has ended,
whichever is longer) after the last dose of study medication and completion of the
follow-up visit.

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

Exclusion Criteria:

- ALT and bilirubin >1.5xupper 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, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- 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 GlaxoSmithKline (GSK) Medical Monitor the medication will not
interfere with the study procedures or compromise subject safety.

- 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 milliliters [mL]) of beer, 5
ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

- Positive results for drugs of abuse.

- Cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 30 days prior to screening.

- 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 Medical
Monitor, contraindicates their participation.

- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at screening or within 3 months prior to first dose of study treatment.

- A positive pre-study drug/alcohol screen.

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

- Where participation in the study would result in donation of blood or blood product in
excess of 500 mL within 56 days.

- 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.

- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility
determination): Heart rate <45 and >100 beats per minute (bpm) for males and <50 and
>100 bpm for females; PR Interval <120 and >220 milliseconds (msec); QRS Interval: <70
and >120 msec; and corrected QT (QTc) interval (Fridericia's) >450 msec.

Evidence of previous myocardial infarction (Does not include ST segment changes associated
with repolarization).

- Any conduction abnormality (including but not specific to left or right complete
bundle branch block, atrioventricular [AV] block [2nd degree or higher],
Wolff-Parkinson-White [WPW] syndrome).

- Sinus Pauses > 3 seconds.

- Any significant arrhythmia which, in the opinion of the principal investigator or ViiV
Healthcare (ViiV)/GSK medical monitor, will interfere with the safety for the
individual subject.

- Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular
ectopic beats).

- Employment with Janssen, ViiV, GSK, or with the Investigator or study site, with
direct involvement in the proposed study or other studies under the direction of
that Investigator or study site, as well as family members of the employees or
the Investigator.