Overview

Study to Evaluate the Effect of GSK3640254 on the Pharmacokinetics of Tenofovir Alafenamide/Emtricitabine

Status:
Completed
Trial end date:
2019-04-30
Target enrollment:
0
Participant gender:
All
Summary
Human immunodeficiency virus (HIV) infection frequently involves combination drug therapy for its treatment; hence, it is important to understand their interactions and resulting changes in exposure which are associated with medications. This is a Phase-1, open-label, fixed-sequence 2-period, one-way drug interaction study to assess the pharmacokinetic (PK), safety, and tolerability of GSK3640254 and Tenofovir alafenamide/emtricitabine (TAF/FTC) when administered alone and in combination in healthy subjects. The study will consist of a screening period of 28 days before the first dose of study intervention followed by 2 sequential treatment periods. Subjects will be administered TAF/FTC 25/200 milligram (mg) once daily (QD) on Days 1 to 14 of Period 1 followed by co-administration of TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 to 7 of Period 2.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
ViiV Healthcare
Treatments:
Emtricitabine
Tenofovir
Criteria
Inclusion Criteria:

- Subject must be 18 to 55 years of age inclusive, at the time of signing the informed
consent.

- Subjects who are healthy as determined by the investigator or medically qualified
designee based on a medical evaluation including medical history, physical
examination, laboratory tests, and cardiac monitoring (history and ECG).

- Body weight >=50.0 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kilograms [kg]
(99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kilograms
per meter square (kg/m^2) (inclusive).

- Male or female; A female subject is eligible to participate if she is not pregnant,
not breastfeeding and not a woman of childbearing potential (WOCBP).

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

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).

- A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or
motility (e.g.,gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic
and/or renal function, that could interfere with the absorption, metabolism and/or
excretion of the study drugs or render the subject unable to take oral study
intervention.

- Any history of significant underlying psychiatric disorder including, but not limited
to, schizophrenia, bipolar disorder with or without psychotic symptoms, other
psychotic disorders, or schizotypal (personality) disorder.

- Any history of major depressive disorder with or without suicidal features or anxiety
disorders, that required medical intervention (pharmacologic or not) such as
hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient
treatment. Subjects with other conditions such as adjustment disorder or dysthymia
that have required shorter term medical therapy (<6 months) without inpatient
treatment and are currently well-controlled clinically or resolved may be considered
for entry after discussion and agreement with the ViiV Medical Monitor.

- Any pre-existing physical or other psychiatric condition (including alcohol or drug
abuse), which, in the opinion of the investigator (with or without psychiatric
evaluation), could interfere with the subject's ability to comply with the dosing
schedule and protocol evaluations or which might compromise the safety of the subject.

- Medical history of cardiac arrhythmias or cardiac disease or a family or personal
history of long QT syndrome.

- History of any kidney disease or current or chronic history of impaired renal function
as indicated by an estimated creatinine clearance <80 milliliters per minute (mL/min).
Creatinine clearance (CrCL) is estimated by either of the following methods: (a) The
Modification of Diet in Renal Disease (MDRD) equation: estimated glomerular filtration
rate (eGFR) (milliliter [mL]/minute [min]/1.73 meter square [m^2]) = 175 x
(SCr)^-1.154 x (Age)^-0.203 x 0.742 [if female] x 1.212 [if African American]
glomerular filtration rate (GFR) is expressed in mL/min/1.73 m^2, SCr is serum
creatinine expressed in milligrams per deciliter (mg/dL), and age is expressed in
years. (b)The Cockcroft-Gault equation: CrCL(mL/min) ={((l40-age) x weight)/(72xSCr)}x
0.85 (if female) CrCL is expressed in mL/min, age is expressed in years, weight is
expressed in kg, and SCr is serum creatinine expressed in mg/dL.

- Presence of Hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior
to starting study intervention.

- Positive Hepatitis C antibody test result at Screening or within 3 months prior to
starting study intervention AND positive on reflex to Hepatitis C ribonucleic acid
(RNA).

- Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.

- ALT >1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a
single screening period to determine eligibility.

- Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%).

- Any acute laboratory abnormality at Screening which, in the opinion of the
investigator, should preclude participation in the study of an investigational
compound.

- Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine
phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides,
etc), and ALT (described above), will exclude a subject from the study unless the
investigator can provide a compelling explanation for the laboratory result(s) and has
the assent of the sponsor. A single repeat of any laboratory abnormality is allowed
within a single screening period to determine eligibility.

- A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine
(indicating active current smoking) at Screening or before the first dose of study
intervention.

- 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 and for the duration of the study.

- Treatment with any vaccine within 30 days prior to receiving study intervention.

- Unwillingness to abstain from excessive consumption of any food or drink containing
grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their
fruit juices within 7 days prior to the first dose of study intervention(s) until the
end of the study.

- Participation in another concurrent clinical study or prior clinical study (with the
exception of imaging trials) 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 study
intervention (whichever is longer).

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

- Any positive (abnormal) response confirmed by the investigator on a screening
clinician- or qualified designee-administered Columbia-Suicide Severity Rating Scale
(C-SSRS).

- Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction,
sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the
opinion of the investigator or VH/GSK Medical Monitor, will interfere with the safety
for the individual subject.

- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility
determination): Heart rate for male: <45 or >100 beats per minute (bpm) and for
females: <50 or >100 bpm; PR interval: <120 or >200 milliseconds (msec); QRS duration:
<70 or >110 msec and QTcF interval for male: >450 msec and for female: >470 msec. A
heart rate from 100 to 110 bpm can be rechecked by ECG or vital signs within 30
minutes to verify eligibility.

- History of regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a
half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL)
measure of spirits.

- Regular use of tobacco- or nicotine-containing products within 3 months 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.