3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

THE PHARMACOKINETICS OF SCH 417690 WHEN ADMINISTERED ALONE AND IN COMBINATION WITH LAMIVUDINE/ZIDOVUDINE

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No.

Guillaume M.¹, Kraan M.², Keung A.², Caceres M.², Sansone A.^2
1Aster Cephac, Paris, France, ²Schering Plough Research Institute, Kenilworth, New Jersey, United States of America

INTRODUCTION: SCH 417690, a novel CCR5 receptor antagonist, is under development for use with other antiretroviral agents. This study evaluated the pharmacokinetics of SCH 417690 together with a fixed-dose combination of lamivudine and zidovudine (Combivir®).

METHODS: Adult healthy volunteers were randomized into open-label treatment groups: (1) SCH 417690 50 mg Q12h, (2) lamivudine/zidovudine (1 tablet, 150 mg/300 mg) Q12h, or (3) SCH 417690 50 mg + lamivudine/zidovudine Q12h. Blood samples for pharmacokinetic analyses were collected on Days 1 and 7 before dosing and up to 96h after dosing. Log-transformed C_max and AUC_0-12 values were analyzed by ANOVA with 90% confidence intervals (CI). Safety was assessed using adverse events (AE), vital signs, electrocardiograms, and laboratory values.

RESULTS: Of 36 subjects enrolled (50% men, 89% Caucasian, median age, 26 y), 35 completed the study. Overall SCH 417690 exposure was not affected by coadministration of lamivudine/zidovudine (C_max, 92% [CI, 77%–110%]; AUC_0-12, 91% [CI, 77%–109%]). Similarly, exposure to zidovudine was not affected by coadministration with SCH 417690 (C_max, 92% [CI, 68%–125%]; AUC_0-12, 93% [CI, 76%–114%]). For lamivudine, AUC was also unaffected when administered in combination with SCH 417690 (AUC_0-12, 96% [CI, 81%–113%]). Lamivudine C_max values were slightly lower when coadministered with SCH 417690 (C_max, 85% [CI, 69%–105%]) but this difference was not considered clinically relevant. Eleven subjects (2 in Group 1, 6 in Group 2, and 3 in Group 3) reported ≥1 AE. The most commonly reported AEs were mild to moderate in intensity and included headache, nausea, and abdominal pain. Vital sign measurements, electrocardiograms, or clinical laboratory values were unremarkable.

CONCLUSIONS: The combination of SCH 417690 50 mg with lamivudine/zidovudine (150 mg/300 mg) was well tolerated, and does not result in a significant drug interaction when given to healthy volunteers for 7 days.

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Basic | TuPe3.1B03 | Angela Sansone
PK and pharmacodynamics

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