LAI115428 is a Phase I, randomized, repeat dose escalation study to determine the safety, tolerability, and PK profile of intramuscular and subcutaneous injections of GSK1265744 in a long acting parenteral (LAP) formulation in healthy subjects. Subjects will be randomized to 3 monthly dosing cohorts and 1 quarterly dosing cohort with either intramuscular or subcutaneous dosing. In the monthly dosing cohorts subjects will receive GSK1265744 alone for 2 months and then in combination with TMC278 long acting parenteral (LA) for 2 months. For the quarterly dosing cohort, 2 quarterly intramuscular doses of GSK1265744 LAP will be given alone. Three dose levels of GSK1265744 will be evaluated partly in combination with TMC278 LA to adequately characterize the GSK1265744 LAP and TMC278 LA safety, tolerability, and PK profile. A total enrolment of approximately 40 healthy subjects is planned for this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
43
30mg tablet
800mg Loading dose given at month 1 dose
200mg maintenance dose give at months 2 - 4
200mg maintenance dose given at months 2 - 4
400mg maintenance dose given at month 2 - 4
1200mg Loading dose given at month 3
600mg Loading dose given at month 4
800mg dose given quarterly (once every) 12 weeks
GSK Investigational Site
Daytona Beach, Florida, United States
GSK Investigational Site
Overland Park, Kansas, United States
GSK1265744 LAP safety and tolerability parameters including the collection of adverse events
Time frame: approximately 25 weeks
GSK1265744 LAP safety and tolerability parameters including change from baseline in clinical laboratory safety assessments
Hematology, Clinical Chemistry and Urinalysis
Time frame: approximately 25 weeks
GSK1265744 LAP safety and tolerability parameters including change from baseline in electrocardiogram (ECG) measurements
Time frame: approximately 25 weeks
GSK1265744 LAP safety and tolerability parameters including change from baseline in vital sign measurements
Blood pressure and heart rate
Time frame: approximately 25 weeks
TMC278 LA safety and tolerability parameters including the collection of adverse events
Time frame: approximately 12 weeks
TMC278 LA safety and tolerability parameters including change from baseline in clinical laboratory safety assessments
Hematology, Clinical Chemistry and Urinalysis
Time frame: approximately 12 weeks
TMC278 LA safety and tolerability parameters including change from baseline in ECG measurements
Time frame: approximately 12 weeks
TMC278 LA safety and tolerability parameters including change from baseline in vital sign measurements
Blood pressure and heart rate
Time frame: approximately 12 weeks
Composite of PK parameters following single and repeat dose intramuscular or subcutaneous administration
Measurements include: area under the plasma concentration time curve over the dosing interval (AUC(0-t)), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration at the end of the dosing interval (Ct).
Time frame: approximately 25 weeks
Composite of GSK1265744 pharmacokinetic parameters following repeat dose oral administration
Measurements include: area under the plasma concentration time curve over the dosing interval (AUC(0-t)), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration at the end of the dosing interval (Ct).
Time frame: approximately 25 weeks
Composite of TMC278 LA pharmacokinetic parameters following single and repeat dose intramuscular administration
Measurements include: area under the plasma concentration time curve over the dosing interval (AUC(0-t)), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration at the end of the dosing interval (Ct).
Time frame: approximately 12 weeks
GSK1265744 LAP safety and tolerability parameters including change from baseline for clinical chemistry assessments (ALT, AST, ALP, Total and Direct Bilirubin).
Time frame: 52 weeks
GSK1265744 oral formulation safety and tolerability parameters including the collection of adverse events
Time frame: 21 days
GSK1265744 oral formulation safety and tolerability parameters including change from baseline in clinical laboratory safety assessments
Hematology, Clinical Chemistry and Urinalysis
Time frame: 21 days
GSK1265744 oral formulation safety and tolerability parameters including change from baseline in ECG measurements
Time frame: 21 days
GSK1265744 oral formulation safety and tolerability parameters including change from baseline in vital sign measurements
Blood pressure and heart rate
Time frame: 21 days
Composite of PK parameters of GSK1265744 LAP and TMC278 LA
Measurements include: apparent clearance (CL/FLAP) following single and repeat dose administration.
Time frame: approximately 12 weeks
Composite of PK parameters following each dose administration at different dose levels for the assessment of dose proportionality and relative exposure
Measurements include: GSK1265744 LAP AUC(0-t), Cmax, and Ct
Time frame: approximately 25 weeks
Composite of PK parameters for GSK1265744 LAP
Measurements include: apparent terminal phase half-life for LAP administration (t½), lambda z as a measure of absorption rate constant if data allow
Time frame: approximately 25 weeks
Composite of PK parameters of TMC278 LA
Measurements include: AUC(0-t), Cmax, and Ct in cohort 2 and 3
Time frame: approximately 12 weeks
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