Dolutegravir (DTG) is an HIV-1 integrase inhibitor approved in the United States, Canada, Australia and EU. A dispersible tablet has been developed for pediatric use as an alternative to the granule formulation, already in development, and the approved film-coated tablet. This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of five dosing regimens: 20 mg DTG pediatric granules (Treatment A) and of DTG 20 mg dispersible tablets (DTG 20 mg DT) after dispersed in: low mineral content(LMC) water (Treatment B); dispersed in CONTREX™ mineral water (Treatment C); dispersed in low mineral content water and consumed after standing for 30 minutes (Treatment D) and dispersed in CONTREX mineral water and consumed after standing for 30 minutes (Treatment E). Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug. CONTREX is a trademark of Nestlé Waters Corporation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
15
Dolutegravir pediatric granules are supplied as 40 grams bulk bottles containing 0.4% weight by weight of dolutegravir to be reconstituted with 73 mL of purified water to yield a dolutegravir concentration of 1.6 milligram / millilitre. 12.5 mL of reconstituted granules contain 20 mg DTG
Dolutegravir is available as 5mg dispersible tablets and can be administered as 4 tablets dispersed in 12.5 mL LMC water and consumed immediately or 4 tablets dispersed in 12.5 mL CONTREX mineral water and consumed immediately or 4 tablets dispersed in 12.5 mL LMC water, allow to stand at room temperature for 30 mins, re-suspend mixture and consumed or 4 tablets dispersed in 12.5 mL CONTREX mineral water, allow to stand at room temperature for 30 mins, re-suspend mixture and consumed
GSK Investigational Site
Overland Park, Kansas, United States
Composite of pharmacokinetic (PK) parameters following single dose administration of DTG 20 mg DT dispersed in LMC water
PK parameters include area under the concentration-time curve from time zero extrapolated to infinite time (AUC \[0-infinity\]) Maximum observed concentration (Cmax) and apparent oral clearance (CL/F)
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in CONTREX mineral water
PK parameters include AUC (0-infinity), Cmax and CL/F
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water with 30-minute holding
PK parameters include AUC (0-infinity), Cmax and CL/F
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water
PK parameters include area under the plasma concentration-time curve from time of dose administration to time of last quantifiable post-dose sample \[AUC(0-t)\]; observed concentration at 24h post-dose (C24); terminal elimination phase half-life (t½); lag time for absorption (tlag); and time to maximum observed concentration (tmax)
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in CONTREX mineral water
PK parameters include AUC(0-t), C24; t½; tlag; and tmax will be evaluated for DTG 20 mg DT
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water with 30-minute holding
PK parameters include AUC(0-t), C24; t½; tlag; and tmax
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Composite of PK parameters following single dose administration of DTG 20 mg DT in CONTREX mineral water with 30-minute holding
PK parameters include AUC (0-infinity), Cmax, CL/F, AUC(0-t); C24; t½; tlag; and tmax
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
Palatability of DTG 20 mg DT
Palatability questionnaire containing 11 questions will be administered to each subject within 10 minutes following the dose of DTG (Period 1 only)
Time frame: Day 1 (Period 1 only)
Safety as assessed by number of subjects with adverse events, change from baseline in vital signs and as toxicity grading of clinical laboratory tests
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Vital signs include blood pressure and heart rate. Clinical laboratory parameters will include hematology and clinical chemistry
Time frame: Up to 14 weeks
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