The phase I clinical trial of Lorediplon, a drug for the treatment of insomnia, has been successfully completed with a best-in-class efficacy profile in terms of maintaining sleep and sleep quality compared with market leader zolpidem.
The trial involved 34 healthy adults, who participated in an advanced phase model of insomnia, in which they were administered with either a single oral administration of Lorediplon at 1mg, 5mg and 10mg doses, zolpidem 10mg and placebo before retiring to bed five hours earlier than usual and remaining in bed until early morning to evaluate the pharmacodynamic effects of Lorediplon.
The findings revealed that the dose related clinical benefits of Lorediplon in measured sleep parameters were either similar to or exceeded zolpidem with regard to the participants sleep duration and quality. Lorediplon proved safe and well tolerated, without any residual effects noted up to 14 hours following dosing. It was furthermore deemed safe and well tolerated in all 129 participants who took part in all Phase I clinical studies.
Antonio Guglietta, R&D director at Ferrer, the drug's manufacturer comments:
"Insomnia remains a common sleep disorder that has both a significant impact on an individual's quality of life and broader impact on society, in terms of reduced productivity and associated healthcare costs. Lorediplon is the first product to enter clinical trials from our CNS discovery program, the aim of which is to deliver differentiated products targeting underserved needs in insomnia and related sleep disorders. Having demonstrated the clinical benefits, safety and tolerability of Lorediplon, we are actively seeking partners to further the worldwide clinical development and commercialization of Lorediplon."
Lorediplon's transpiring clinical and preclinical profile advocates further development as a possible best-in-class non-benzodiazapine (BZD) therapy for sleep insomnia, regarding its efficacy in improved sleep maintenance and quality, tolerability and absence of next-day residual effects linked to other treatments in this class.
Lorediplon, taken orally, has several granted and pending patents. The drug is available for further development and global commercialization by Ferrer.
Insomnia is a common sleep disorder in which individuals experience either experience difficulty in falling or remaining asleep, or they sleep for abnormal durations or whose restorative quality of sleep is abnormal. The frequency of the disorder varies, with estimates of 80% of the population experiencing transient insomnia lasting less than two weeks per year to 15% of the population with chronic insomnia. Not being able to sleep through the night is substantially more frequent compared with sleep onset insomnia.
The disorder is often accompanied or caused by other co-morbid conditions and is linked to substantial night- and day-time symptoms, such as tiredness, difficulty in concentrating and being irritable, more frequent use of the healthcare system, reduced work productivity, lower quality of life, as well as impairments of memory, mood and cognitive function.
The major hypnotic drugs that are presently available on the market are gamma-Amino Butyric Acid A (GABAA) receptor modulators that potentiate GABA, the main inhibitory neurotransmitter in the brain, and enable people to fall asleep and sometimes maintain sleep throughout the night. However, their use is linked to changes in sleep structure, a decrease in psychomotor and cognitive functioning, dependency, withdrawal symptoms and a higher incidence of falls and apnea.
Lorediplon is a novel, longer acting non-BZD hypnotic drug, which balances the GABAA receptor. It is particularly potent at the alpha1-subunit, which is believed to be the most relevant target of the GABAA receptor for insomnia treatment. In preclinical and clinical studies Lorediplon has shown a potent hypnotic profile and extended systemic half-life that could offer possible clinical benefits in maintaining sleep and sleep structure in comparison to other non-BZD receptor agonists, such as zolpidem. Lorediplon has also displayed a good preclinical and clinical safety and tolerability profile, with no next-day residual effects and other side effects linked to other treatments available in this class. Lorediplon's favorable risk/benefit profile grants further development for the treatment of insomnia.
Written by Petra Rattue