Tobira Therapeutics, a clinical stage biotechnology company committed to research and product discovery for the treatment of life-threatening and life-altering infectious diseases, today announced pharmacokinetic data and results from two double-blind, placebo-controlled studies of TBR-652 in eighty-four healthy volunteers. The two studies, a single-ascending dose (SAD) study and the multiple-ascending dose (MAD) study, were undertaken to assess the pharmacokinetics, safety and tolerability of TBR-652 in two tablet formulations under fasted and fed conditions, respectively. In the SAD study 2 cohorts of 12 subjects were randomized per dose level; each subject received up to 3 single escalating doses of study drug. Dosing followed an overnight fast of at least 8 hours. In the MAD study, 5 dose groups of 12 subjects each were randomized to receive drug daily for 10 days. Doses were either in the same formulation as the SAD study (F1) or a newer formulation (F2). Doses were taken within 10 minutes after completion of a standard high-fat breakfast. Subjects in both studies were followed for 10 days after the last dose of TBR-652.
TBR-652 was readily absorbed in both tablet formulations achieving mean peak plasma concentrations in 4-6 hours. A 25 mg/day F1 or F2 tablet achieved plasma exposures greater than the target therapeutic level of 2ng/mL projected from in vitro studies of TBR-652. TBR-652 was eliminated from plasma with linear kinetics and similar half-lives (mean approximately 35-40 hours) across dose levels. This elimination half-life is sufficiently long to support once-daily dosing.
TBR-652 was well-tolerated at single daily doses up to 800 mg and once-daily doses of up to 200 mg for 10 days. Headache, diarrhea, abdominal pain and nausea were the most commonly encountered treatment-emergent events; all AEs resolved by the end of both studies. "The results from these two Phase II studies provide further basis for the continued development of TBR-652 for the treatment of HIV," said James Sapirstein, CEO. "Providing patients with well-tolerated, once-daily dosing options is a priority with our development programs. We look forward to the results from our on-going proof of concept trial of TBR-652."
These data were presented at the 12th( )European AIDS Conference (EACS), held November 11-14, 2009 in Cologne, Germany. The poster presentation can be viewed at www.tobiratherapeutics.com.
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