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APD125 is an oral drug candidate discovered by Arena that is beingevaluated for the treatment of insomnia in patients who have difficultymaintaining sleep after initial sleep onset. When compared to placebo in thePhase 2a clinical trial, patients treated with APD125 experiencedstatistically significant improvements in polysomnographic (PSG) measurementsof sleep maintenance, or the ability to maintain sleep during the night afterfalling asleep. These improvements were achieved without any next dayimpairment of cognition or coordination.
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"APD125 is a potential next generation treatment for improving sleepmaintenance that could meet the needs of many patients looking to achievebetter 'quality sleep'," stated Dr. Thomas Roth of Henry Ford Hospital, whointerpreted the PSG data for the Phase 2a trial. "In the trial, APD125 clearlydemonstrated robust sleep maintenance properties without any apparent patternof 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 PSGendpoints measuring improvements in sleep maintenance, including wake aftersleep onset (WASO) and wake time during sleep (WTDS). WASO, the primaryendpoint, 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 by51.7 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 by46.1 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 improvedsignificantly for both doses and time points (p<0.0001 at both N 1/2 and N 6/7at 10 mg and 40 mg for both variables). Changes in the number of awakeningswere 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 alsoevidenced by a significant reduction in wake time during the middle of thenight (hours three through six). APD125 also significantly increased the timespent in deep (Stage 3 and 4) sleep while decreasing the amount of time spentin the lighter stages of sleep (Stages 1 and 2), providing further evidencefor the sleep maintenance properties of APD125. Time in REM sleep was notmeaningfully affected.
Treatment with APD125 was well tolerated, with no reports of seriousadverse events and no emerging safety findings as compared to placebo. No nextday impairment of cognition or coordination was observed and there was noevidence 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 andefficacy of nighttime dosing in patients with primary insomnia. The trialevaluated standard PSG measurements of sleep, such as WASO, WTDS, number ofawakenings, number of arousals, total sleep time and latency to persistentsleep, and enrolled a total of 173 male and female patients, ages 18-64, in24 sleep research centers in the United States. To qualify for enrollment,patients were required to have
