ARENA ANNOUNCES PHASE I CLINICAL TRIAL RESULTS

Arena Pharmaceuticals announced top-line results from its Phase I clinical trials of APD125, Arena's orally administered, internally discovered drug candidate for the treatment of insomnia.

APD125 was well-tolerated at all doses investigated. The data demonstrated a robust and statistically significant increase in the amount of deep, or slow wave, sleep and a positive signal in other sleep maintenance parameters, which may distinguish APD125 from currently available sleep therapeutics. APD125 may have extended sleep onset latency in normal volunteers. APD125 is a novel and highly selective inverse agonist of the 5-HT2A serotonin receptor.

The Phase I program consisted of three clinical trials, APD125-001, APD125-002 and APD125-003, designed to evaluate the single and multiple dose safety and pharmacokinetics of APD125 in normal volunteers. Additionally, it evaluated the pharmacodynamics of nighttime dosing using polysomnography to assess effects on sleep patterns in normal volunteers.

The APD125-001 trial enrolled 45 healthy male volunteers in a randomized, double-blinded, placebo-controlled study evaluating the safety, tolerability and pharmacokinetics of single escalating doses of APD125 in five cohorts of nine volunteers each. Six volunteers in each cohort received one daytime dose of APD125 while three volunteers received placebo. The first cohort was administered 10 mg of APD125, which was subsequently increased to 20 mg, 40 mg, 80 mg and 160 mg in each successive cohort after safety and pharmacokinetics were evaluated in the prior cohort. In addition to safety and pharmacokinetic evaluation, this trial included waking electroencephalographic (EEG) readings taken after dosing to examine brain wave activity to help guide dose selection in the 002 trial.

Top-line results demonstrated that APD125 was well-tolerated at all doses investigated. Pharmacokinetics were related to dose at the 10 mg, 20 mg and 40 mg doses, demonstrating good dose proportionality. At 40 mg, the maximum concentration in the body, or Cmax, of APD125 plateaued; there were no significant differences in Cmax among the 40 mg, 80 mg and 160 mg doses. At 80 mg, the total overall exposure, or AUC (0-inf), of APD125 also plateaued; the pharmacokinetics at the 160 mg dose were generally similar to the 80 mg dose. The maximum tolerated dose was not defined in the trial and higher doses were not tested because of the similar pharmacokinetics observed at the 80 mg and 160 mg doses. At the 40 mg dose the drug plasma half life was 10.8 hours and the mean residence time, or the average time the drug resided in the blood, was 6.8 hours.