[WePe3.3C15] Pharmacokinetic interaction between the novel non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 and tenofovir disoproxil fumarate (TDF) in healthy volunteers

3rd International AIDS Society Conference on HIV Pathogenesis and Treatment

Rio de Janeiro - July 24 - 27, 2005

PHARMACOKINETIC INTERACTION BETWEEN THE NOVEL NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) TMC278 AND TENOFOVIR DISOPROXIL FUMARATE (TDF) IN HEALTHY VOLUNTEERS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.3C15

Hoetelmans R., Kestens D., Stevens M., Peeters M., Williams P., Bastiaanse L., Buffels R., Woodfall B.
Tibotec, Mechelen, Belgium

INTRODUCTION: TMC278 is a novel NNRTI with potent in vitro activity against wild-type HIV and with a high genetic barrier to development of resistance. TMC278 is administered at low dosages q.d. A study was conducted to evaluate the interaction between TMC278 and TDF.

METHODS: TMC278-C104 was an open-label, one-sequence, 2-way randomized crossover trial to investigate the steady-state interaction between TMC278 and TDF in 16 healthy volunteers. TMC278 was administered as a tablet. During Session I, TMC278 150 mg q.d. was administered from day 1 – 8. After a washout period of 14 days, Session II consisted of TDF 300 mg q.d. from day 1 – 16. TMC278 150 mg q.d. was co-administered from day 9 – 16 in 8 subjects randomized to Group 1 and from day 1 – 8 in 8 subjects randomized to Group 2. All doses were taken with food. Pharmacokinetic profiles of TMC278 and tenofovir were assessed during 24 hours.

RESULTS: 15 subjects completed the study. When combined with TDF, TMC278 AUC_24h was 102% (90% CI 88 – 119%) compared to administration of TMC278 alone. TMC278 C_max and C_min were 97% (90% CI 82 – 115%) and 100% (90% CI 84 – 118%), respectively. Tenofovir AUC_24h was 124% (90% CI 116 – 131%) when combined with TMC278 compared to administration of tenofovir alone. Tenofovir C_max and C_min were 121% (90% CI 108 – 136%) and 124% (90% CI 115 – 133%), respectively. TMC278 and TDF were generally safe and well tolerated.

CONCLUSIONS: The interaction study between TMC278 and TDF showed that the pharmacokinetics of TMC278 are not affected when combined with TDF. Exposure to tenofovir was statistically significantly increased by 24% when combined with TMC278. This interaction is not clinically relevant. The combination of TMC278 and TDF was generally safe and well tolerated. No dose adjustments are necessary when TMC278 and TDF are combined. TMC278 is currently being studied in Phase IIb with TDF and other NRTIs.

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050724
Clinical | WePe3.3C15 | Richard Hoetelmans
Drug Interactions

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