GSK1349572 Drug Interaction Study With Efavirenz
GSK1349572 is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment of HIV infection. As GSK1349572 development progresses, it may be dosed with non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) including efavirenz (EFV, Sustiva). Efavirenz is a known inducer of CYP3A4. GSK1349572 is primarily metabolized via UGT1A1, however it also has a CYP component to its metabolism, thus a drug interaction between GSK1349572 and EFV is likely. A previous study showed that another NNRTI, etravirine which is also a known inducer of CYP3A and UGT, reduced GSK1349572 exposure significantly. GSK1349572 is not an inhibitor or inducer of CYP3A and is not expected to have impact on pharmacokinetics (PK) of EFV.
This study will investigate the dose proportionality between single doses of 50mg and 100mg of GSK1349572 and will compare steady-state plasma PK, safety and tolerability of GSK1349572 50 mg every 24h (q24h) with and without efavirenz 600 mg q24h. Approximately 12 subjects will receive a single dose of GSK1349572 100 mg (Treatment A) in Period 1 followed by a washout of greater than or equal to 6 days. In Period 2 subjects will receive GSK1349572 50mg q24h for 5 days (Treatment B). Subjects will then be administered GSK1349572 50mg q24h in the morning in combination with EFV 600 mg q24h (Treatment C) in the evening for 14 days in Period 3. There will be no washout between Periods 2 and 3. Safety evaluations and serial PK samples for GSK1349572 will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug.
This study will be conducted at one center in the US, with healthy adult male and female subjects.
Infections, Human Immunodeficiency Virus and Herpesviridae
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open Label, Single Sequence, Three Period Study to Evaluate the Single Dose Pharmacokinetics of GSK1349572 100mg Versus 50mg and the Effect of Efavirenz 600mg Once Daily on the Pharmacokinetics, Safety and Tolerability of GSK1349572 50mg Once Daily in Healthy Adult Subjects (ING114005)|
- Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
- Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days. [ Time Frame: 19 days ] [ Designated as safety issue: No ]
- Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, ECG, and vital signs assessments. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Plasma GSK1349572 single dose PK parameters: tmax and tlag, following administration of GSK1349572 100mg and 50mg [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
- Plasma GSK1349572 steady-state PK parameters: tmax, tmin, CL/F, and t½, following 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days. [ Time Frame: 19 days ] [ Designated as safety issue: No ]
|Study Start Date:||March 2010|
|Study Completion Date:||May 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
Subjects will receive a single dose of GSK1349572 100 mg in Period 1 followed by a washout of at least 6 days. Subjects will then receive GSK1349572 50 mg once a day for 5 days in Period 2. Period 3 will begin immediately after Period 2. In Period 3 subjects will receive GSK1349572 50 mg once a day in the morning and Efavirenz 600 mg once a day at bedtime for 14 days. There will be a screening visit up to 30 days before Period 1 and a follow up visit 7-14 days after the end of Period 3.
GSK1349572 is an experimental drug under development for the treatment of HIV. It is in the class of integrase inhibitors.Drug: Efavirenz
Efavirenz is a drug that has been approved by the FDA for the treatment of HIV. It is in the class of non-nucleoside reverse trancriptase inhibitors.
Other Name: SUSTIVA. SUSTIVA is a registered trademark of Bristol-Myers Squibb
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01098526
|United States, New York|
|GSK Investigational Site|
|Buffalo, New York, United States, 14202|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|