APD125 Trial For Insomnia Treatment Shows Positive Results
Dr. Thomas Roth of Henry Ford Hospital presented data from Arena's positive Phase 2a clinical trial of APD125 for the treatment of insomnia in an oral presentation at the SLEEP 2008 22nd Annual Meeting of the Associated Professional Sleep Societies in Baltimore, Maryland.
APD125 is an oral drug candidate discovered by Arena that is being evaluated for the treatment of insomnia in patients who have difficulty maintaining sleep after initial sleep onset. When compared to placebo in the Phase 2a clinical trial, patients treated with APD125 experienced statistically significant improvements in polysomnographic (PSG) measurements of sleep maintenance, or the ability to maintain sleep during the night after falling asleep. These improvements were achieved without any next day impairment of cognition or coordination.
"APD125 is a potential next generation treatment for improving sleep maintenance that could meet the needs of many patients looking to achieve better 'quality sleep'," stated Dr. Thomas Roth of Henry Ford Hospital, who interpreted the PSG data for the Phase 2a trial. "In the trial, APD125 clearly demonstrated robust sleep maintenance properties without any apparent pattern of side effects associated with the drug."
Arena is currently evaluating the effects of APD125 on patients' subjective assessment of sleep in a Phase 2b study.
APD125 Phase 2a Study Results
In a Phase 2a clinical trial, APD125 significantly improved several PSG endpoints measuring improvements in sleep maintenance, including wake after sleep onset (WASO) and wake time during sleep (WTDS). WASO, the primary endpoint, decreased from baseline by 52.5 minutes (10 mg) and 53.5 minutes (40 mg) at nights one and two (N 1/2) (p<0.0001 for both vs. placebo) and by 51.7 minutes (p=0.01) and 48.0 minutes (p=0.2) at nights six and seven (N 6/7), respectively. WTDS decreased from baseline by 45.8 minutes (10 mg) and 46.6 minutes (40 mg) at N 1/2 (p<0.0001 for both vs. placebo) and by 46.1 minutes (10 mg) and 46.9 minutes (40 mg) at N 6/7 (p<0.001 for both vs. placebo).
Importantly, the number of awakenings and number of arousals improved significantly for both doses and time points (p<0.0001 at both N 1/2 and N 6/7 at 10 mg and 40 mg for both variables). Changes in the number of awakenings were 0.0, -2.5 and -3.1 at N 1/2 and -0.9, -2.3 and -2.5 at N 6/7 for placebo, 10 mg and 40 mg, respectively. Changes in the number of arousals were +3.8, -5.8 and -8.1 at N 1/2 and +2.5, -4.8 and -6.7 at N 6/7 for placebo, 10 mg and 40 mg, respectively. The beneficial effect of APD125 was also evidenced by a significant reduction in wake time during the middle of the night (hours three through six). APD125 also significantly increased the time spent in deep (Stage 3 and 4) sleep while decreasing the amount of time spent in the lighter stages of sleep (Stages 1 and 2), providing further evidence for the sleep maintenance properties of APD125. Time in REM sleep was not meaningfully affected.
Treatment with APD125 was well tolerated, with no reports of serious adverse events and no emerging safety findings as compared to placebo. No next day impairment of cognition or coordination was observed and there was no evidence of treatment withdrawal symptoms.
APD125 Phase 2a Study Design
The Phase 2a trial of APD125 was a randomized, double-blind, placebo-controlled, three-way crossover study evaluating the safety and efficacy of nighttime dosing in patients with primary insomnia. The trial evaluated standard PSG measurements of sleep, such as WASO, WTDS, number of awakenings, number of arousals, total sleep time and latency to persistent sleep, and enrolled a total of 173 male and female patients, ages 18-64, in 24 sleep research centers in the United States. To qualify for enrollment, patients were required to have paired screening PSGs that demonstrated an average WASO greater than or equal to 60 minutes, with neither PSG less than 45 minutes.
Every patient received both active doses of APD125 (10 mg and 40 mg) and placebo in random order for one week, separated by a seven to nine day washout period between each dosing period. Efficacy was measured objectively by averaging PSG values for N 1/2 and for N 6/7, versus baseline values obtained by averaging results from the screening PSGs.