To Assess the Relative Bioavailability (BA) of TRIUMEQ® and Dolutegravir and Lamivudine (DTG/3TC) Pediatric Dispersible Tablet Formulations in Healthy Volunteers
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Treatment A; Treatment B; Treatment C; Treatment D; Treatment E; Treatment F
Intervention description: TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.; TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets; TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.; DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and
1 tablet 3TC (300 mg), orally as direct-to-mouth.; DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.; DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 2-part study with 3-TPs each. Part 1, compares relative BA of TRIUMEQ dispersible tablets for pediatric populations (DTG, 5 milligram [mg]/abacavir [ABC] 60 mg/3TC 30 mg), when administered as direct-to-mouth and when dispersed into purified water, with adult TRIUMEQ conventional tablet (DTG 50 mg/ABC 600 mg/3TC 300 mg), administered as direct-to-mouth (reference). Additionally, part 2 will compare relative BA of DTG/3TC (DTG 5 mg/3TC 30 mg), dispersible tablets for pediatric populations, when administered as direct-to mouth and when dispersed into purified water, with adult DTG (50 mg) and 3TC (300 mg) conventional tablets, when administered as direct-to-mouth (reference). Each TP, in Part 1 and 2 will have, wash-out period of 7-days (with minus 4 hours) between each single dose, for flexible dosing. During TPs, subjects will be admitted, to clinic on Day-1, following completion of last study procedure on Day 4, post which follow-up visit conducted, 7 to 10 days after last dose.
Masking: None (Open Label)
Masking description: This is an open-label study in healthy volunteers.
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pediatric dispersible tablets; Bioavailability

Summary:

      This is a 2-part, single-dose, open label, randomized 3-way cross-over study to compare BA of
      pediatric study drugs TRIUMEQ and (DTG/3TC) in healthy volunteers under fasted conditions.
      Study will be conducted in 2-parts. Each part 1 and part 2 will comprise of 3-treatment
      periods (TP) where Part 1, will assess BA, of pediatric TRIUMEQ dispersible tablets with an
      adult TRIUMEQ conventional tablet formulation and Part 2, will assess BA, of pediatric
      DTG/3TC dispersible tablets with adult DTG and 3TC conventional tablets formulation. Total
      duration of study is 9-weeks and will be conducted in approximately 36 subjects. The 2-parts,
      may be run in parallel as they are independent of each other. TRIUMEQ is a registered
      trademark of GlaxoSmithKline group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between 18 and 65 years of age, inclusive, at the time of signing the informed
             consent.

          -  Healthy subjects 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 and ECG).

          -  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 per square meter (kg/m^2) (inclusive).

          -  Male and female subjects where the male subjects must agree to use contraception
             during the TP and for at least 2 weeks plus an additional 90 days (a spermatogenesis
             cycle) after the last dose of study treatment and refrain from donating sperm during
             this period. For the female subjects, female subject is eligible to participate if she
             is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG]
             test), not lactating, and at least 1 of the following conditions applies: Female with
             non-reproductive potential, defined as Premenopausal females with one of the following
             like documented tubal ligation, documented hysteroscopic tubal occlusion procedure
             with follow-up confirmation of bilateral tubal occlusion, documented hysterectomy,
             documented bilateral oophorectomy, the Postmenopausal defined as 12 months of
             spontaneous amenorrhea [in questionable cases a blood sample with simultaneous
             follicle stimulating hormone and estradiol levels consistent with menopause. 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 enrolment; Females with
             reproductive potential and agrees to follow one of the options for avoiding pregnancy
             in females of reproductive potential, from 30 days prior to the first dose of study
             medication and until 2 weeks after dosing with study medication and completion of the
             follow-up visit; the investigator is responsible for ensuring that subjects understand
             how to properly use these methods of contraception; All female subjects participating
             in the study should be counselled on safer sexual practices including the use and
             benefit/risk of effective barrier methods (e.g., male condom) and on the risk of human
             immune virus (HIV) transmission to an uninfected partner.

          -  Subjects capable of giving signed informed consent.

          -  For participation in Part 1, documentation that the subject is negative for the human
             leukocyte antigen (HLA)-B*5701 allele.

        Exclusion Criteria:

          -  The medical conditions included where ALT and bilirubin >1.5 × upper limit of normal
             (ULN) (isolated bilirubin >1.5 × ULN 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).

          -  Exclusion criteria for screening ECG (a single repeat is allowed for eligibility
             determination) where the heart rate for the male subjects be <45 and >100 beats per
             minute (bpm) and that for females be < 50 and > 100 bpm; the PR interval for both be <
             120 and > 220 millisecond (msec); the QRS interval be < 70 and > 120 msec and the
             corrected Q-T interval (QTc) obtained using the Fridericia's formula (QTcF) be >450
             msec ; ECG with 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 block
             [2nd degree or higher], Wolf-Parkinson-White syndrome); Sinus pauses > 3 seconds; any
             significant arrhythmia which, in the opinion of the principal investigator or
             ViiV/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety of the
             individual subject; non-sustained or sustained ventricular tachycardia (3 consecutive
             ventricular ectopic beats).

          -  Subjects with use of prior or concomitant therapy who are unable to refrain from the
             use of prescription (e.g., dofetilide) 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 ViiV
             Healthcare 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 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces
             (150 mL) of wine, or 1.5 ounces (45 mL) of 80 proof distilled spirits.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 1 month prior to screening.

          -  Contraindications like 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. The subject has
             participated in a clinical trial and has received an investigational product (IP)
             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 IP
             (whichever is longer).

          -  The subject has participated in a clinical trial and has received an IP 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 IP (whichever is
             longer).

          -  Creatinine clearance (CrCL) < 90 mL per minute.

          -  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/cotinine screen.

          -  A positive test for HIV antibody.

          -  Where participation in the study would result in donation of blood or blood product in
             excess of 500 mL within 60 days.

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.