Circadin® is approved for marketing in the EU as a patent-protected 2 mg prolonged-release melatonin formulation. It mimics the physiological secretion profile of melatonin. Neurim's database has shown that elderly patients suffering from primary insomnia secrete significantly lower levels of melatonin than those with good sleep quality. Thus the rationale for the use of Circadin® is to reconstitute the decreased melatonin levels in this patient population. Consequently, patients are able to improve the quality of their sleep and subsequently improve day-time functioning. This treatment approach thus fundamentally differs from currently available CNS-depressant hypnotics that act through the GABA-A receptor.

The clinical development of Circadin® is based on the observation that it improves sleep quality in elderly insomnia patients as shown in controlled clinical studies by Garfinkel et al., Leger et al. and by Haimov et al. To date it has undergone a full preclinical and clinical development program including multicenter trials conducted by reputable CROs. Circadin® is extremely well tolerated and safe as reflected by the low rate of drop-outs in clinical trails and of adverse events in our clinical safety database. Circadin® was found effective in improving quality of sleep and sleep latency while also improving day time functioning. Circadin® was not associated with impairment of memory, vigilance, and driving performance as compared with placebo and other hypnotics as shown in studies by Paul et al and had no discernible withdrawal symptoms.

In exploratory studies, Circadin® also improves sleep quality in patients with chronic schizophrenia as shown in a randomised double-blind clinical trial by Shamir et al. as well as in patients with major depressive disorder as shown in a double-blind study by Dolberg et al. and an open-label study by Dalton et al. and children with sleep-wake cycle disorders as shown in a studies by Jan et al and De Leersnyder et al. In addition, Circadin® as add-on to antihypertensive therapy improved blood pressue control in patients with nocturnal hypertension as shown in a randomised double-blind placebo controlled study by Grossman et al.

The effects of Circadin® versus placebo treatment were assessed in a multi-center randomized placebo-controlled study. Circadin® is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older-suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation Lemoine et al.

Prolonged-release melatonin treatment results in significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency and quality of life in primary insomnia patients aged years and over as shown in double-blind study by   Wade et al.