Neurim Pharmaceuticals Ltd released positive results from a multiple ascending dose (MAD), safety, pharmacokinetics, and pharmacodynamics phase Ib study of its new investigational insomnia drug Neu-P11.

A first-in-human (FIH), single ascending dose study completed in June 2010 demonstrated the safety tolerability, pharmacokinetics, and pharmacodynamics of Neu-P11 in 32 healthy male volunteers. Ascending single Neu-P11 doses of 5 mg, 20 mg, 50 mg, and 200 mg were found to be safe and well tolerated in subjects. Sleep promoting effects were also demonstrated. The most frequently reported adverse effect was headache of mild intensity and short duration.

The MAD study was a double-blind placebo-controlled crossover multiple ascending dose study of Neu-P11 tolerability, pharmacokinetics, and pharmacodynamics in 25 insomnia patients aged 18-80. Patients were treated by ascending doses of 2 mg, 5 mg, 20 mg, and 50 mg Neu-P11 and placebo nightly for 6 days with 1-month washout between treatments.

The study confirmed that Neu-P11 is generally safe and well tolerated with a pharmacokinetic profile typical of a short acting hypnotic drug (T1/2 1.2-2.9 hrs) with no evidence of accumulation. Despite the relatively small number of patients (6/group), the data demonstrated significant dose-dependent improvement in sleep continuity outcomes (fragmentation index and number of awakenings) with Neu-P11 compared to placebo. Sleep latency, subjective outcomes of sleepiness (Karolinska Sleepiness Scale), and sleep quality (National Sleep Foundation Sleep Diary) also tended to improve at the higher doses. Neu-P11 had no detrimental effects on memory consolidation or sleep structure.

Together with the preclinical findings, the results of this study make Neu-P11 a plausible candidate for the treatment of primary and comorbid insomnia.

“We are encouraged by these results” said Dr Moshe Laudon, director of drug discovery at Neurim. “These findings indicate that the compound was safe and well-tolerated across a broad dose range and provides a proof of principle of efficacy of this drug in insomnia.”

Dr Amnon Katz, manager of clinical trials at Neurim, said, “We’re moving rapidly toward the initiation of our Phase II insomnia trial with Neu-P11. We’ve built the groundwork for getting into Phase II quickly with solid pharmacodynamic results from our prior single ascending dose study in healthy volunteers and this multiple ascending dose study in patients.”