PII‐2

AIM Evaluate the effect of buprenorphine transdermal system (BTDS) 10 mg and 2 × 20 mg on QT/QTc intervals in healthy subjects, compared with placebo and oral moxifloxacin 400 mg. METHODS Randomized, placebo‐ and positive‐controlled, parallel‐group, thorough QTc study in 132 healthy adults (18 to 55 years), BMI<30 kg/m 2 , normal cardiac conduction, and resting heart rate 50–85 bpm. Safety was assessed with adverse event reports, clinical laboratory results, vital signs and SpO 2 , physical examinations, ECGs, and telemetry. RESULTS BTDS 10 was not associated with a change in QTci. However, BTDS 2 × 20 (supratherapeutic dose) resulted in a prolongation comparable to moxifloxacin 400 mg (Day 13). Mean (90% CI) changes from baseline in QTci over 24 hours compared with placebo were 7.6 (5.4, 9.9) and 5.9 (3.3, 8.4) for single 400 mg moxifloxacin doses on Days 6 and 13 respectively, and 0.4 (−1.8, 2.6) and 5.9 (3.4, 8.4) for BTDS 10 and BTDS 2 × 20, respectively. No subjects had maximum QT/QTc intervals ≥480 msec, and no subject had increases in QTci ≥30 msec. Most common adverse events in BTDS group were nausea, headache, constipation, vomiting, and dizziness. No changes of potential clinical importance were observed in vital signs, ECGs (except QTc), or laboratory tests. CONCLUSIONS BTDS 10 does not increase QTci in healthy subjects. BTDS 2 × 20 increases the QTci in healthy subjects by an amount comparable to 400 mg moxifloxacin. Most BTDS subjects were successfully titrated to the supratherapeutic dose of 2 x BTDS‐20. Clinical Pharmacology & Therapeutics (2005) 79 , P35–P35; doi: 10.1016/j.clpt.2005.12.127