Clinical trial NCT03441984: To Assess the Relative Bioavailability (BA) of TRIUMEQ® and Dolutegravir and Lamivudine (DTG/3TC) Pediatric Dispersible Tablet Formulations in Healthy Volunteers
Official title: A 2-Part, Phase I, Single-Dose, 3-Period Crossover Relative Bioavailability Study of a Pediatric TRIUMEQ Dispersible Tablet and Pediatric Dolutegravir and Lamivudine (DTG/3TC) Fixed Dose Combination Dispersible Tablet Formulations as Compared With Adult Tablets in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Pediatric dispersible tablets
Bioavailability
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
name: Pharmaceutical Product Development (PPD), Inc
First posted: 2018-02-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC From Time of Dose to Last Measurable Concentration (AUC[0-t]) in Part 1 of DTG
timeFrame: Pre-dose,15 and 30 minutes,1 ,1.5 ,2 ,2.5 ,3 ,4 ,5 ,6 ,8 ,12 ,16 ,24 ,48 and 72 hours post-dose of each treatment period
measure: Maximum Observed Concentration (Cmax) in Part 1 of DTG in Plasma
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-inf) in Part 1 of ABC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-t) in Part 1 of ABC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Cmax in Part 1 of ABC in Plasma
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-inf) in Part 1 of 3TC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC (0-t) in Part 1 of 3TC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Cmax in Part 1 of 3TC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-inf) in Part 2 of DTG in Plasma
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-t) in Part 2 of DTG
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Cmax in Part 2 of DTG in Plasma
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-inf) in Part 2 of 3TC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-t) in Part 2 of 3TC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Cmax in Part 2 of 3TC
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Secondary outcomes:
measure: AUC From Time of Dose to 24 Hours (AUC[0-24]) of DTG in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Time to Maximum Concentration (Tmax) of DTG in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Time of Last Quantifiable Concentration (Tlast) of DTG in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Apparent Oral Clearance (CL/F) of DTG in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Apparent Volume of Distribution (Vz/F) of DTG in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Observed Concentration at 24 Hours Postdose (C24) of DTG in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Last Observed Quantifiable Concentration (Ct) of DTG in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Terminal Elimination Phase Half-life (t½) of DTG in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Lag Time for Absorption (Tlag) of DTG in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-24) of ABC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Tmax of ABC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Tlast of ABC in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: CL/F of ABC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Vz/F of ABC in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: C24 of ABC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Ct of ABC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: T½ of ABC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC(0-24) of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Tmax of 3TC in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Tlast of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: CL/F of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Vz/F of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: C24 of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Ct of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: T½ of 3TC in Plasma in Part 1
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC (0-24) of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Tmax of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Tlast of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: CL/F of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Vz/F of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: C24 of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Ct of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: T½ of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Tlag of DTG in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: AUC (0-24) of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Tmax of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Tlast of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: CL/F of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Vz/F of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: C24 of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period
measure: Ct of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: T½ of 3TC in Plasma in Part 2
timeFrame: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Part 1
timeFrame: Up to Day 33
measure: Number of Participants With AEs and Serious Adverse Events SAEs in Part 2
timeFrame: Up to Day 33
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotranferase (AST) and Creatinine Phosphokinase (CPK)
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin
timeFrame: Day 2 of each treatment period
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: ALT, ALP, AST and CPK
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin
timeFrame: Baseline (Day -1) and Day 2
measure: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Erythrocytes in Part 1
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Hemocrit in Part 1
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Hemoglobin in Part 1
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Erythrocyte Mean Corpuscular Volume in Part 2
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Erythrocytes in Part 2
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Hemocrit in Part 2
timeFrame: Day 2 of each treatment period
measure: Absolute Values for Hemoglobin in Part 2
timeFrame: Day 2 of each treatment period
measure: Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 1
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Erythrocytes in Part 1
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Hemocrit in Part 1
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Hemoglobin in Part 1
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 2
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Erythrocytes in Part 2
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Hemocrit in Part 2
timeFrame: Baseline (Day -1) and Day 2
measure: Change From Baseline Values for Hemoglobin in Part 2
timeFrame: Baseline (Day -1) and Day 2
measure: Number of Participants With Abnormal Urinalysis Parameter in Part 1
timeFrame: Up to Day 33
measure: Number of Participants With Urine Potential of Hydrogen (pH)-Part 1
timeFrame: Up to Day 33
measure: Number of Participants With Abnormal Urinalysis Parameter in Part 2
timeFrame: Up to Day 33
measure: Number of Participants With Urine Potential of Hydrogen (pH)-Part 2
timeFrame: Up to Day 33
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Part 1
timeFrame: Baseline (Day -1)
measure: Number of Participants With Abnormal ECG Findings in Part 2
timeFrame: Baseline (Day -1)
measure: Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Part 1
timeFrame: Day 1 at 4 hours post intervention and Day 2 of each treatment period
measure: Absolute Values for Pulse Rate in Part 1
timeFrame: Day 1 at 4 hours post intervention and Day 2 of each treatment period
measure: Absolute Values for Temperature in Part 1
timeFrame: Day 1 at 4 hours post intervention dose and Day 2 of each treatment period
measure: Absolute Values for SBP and DBP of Part 2
timeFrame: Day 1 at 4 hours post intervention dose and Day 2 of each treatment period
measure: Absolute Values for Pulse Rate in Part 2
timeFrame: Day 1 at 4 hours post intervention dose and Day 2 of each treatment period
measure: Absolute Values for Temperature in Part 2
timeFrame: Day 1 at 4 hours post intervention dose and Day 2 of each treatment period
measure: Change From Baseline in SBP and DBP of Part 1
timeFrame: Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2
measure: Change From Baseline in Pulse Rate of Part 1
timeFrame: Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2
measure: Change From Baseline in Temperature of Part 1
timeFrame: Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2
measure: Change From Baseline in SBP and DBP of Part 2
timeFrame: Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2
measure: Change From Baseline in Pulse Rate in Part 2
timeFrame: Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2
measure: Change From Baseline in Temperature in Part 2
timeFrame: Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.