Date: 2016-07-07
Type of information: Initiation of development program
phase: 2
Announcement: initiation of development program
Company: Actelion (Switzerland)
Product: dual orexin receptor antagonist (DORA)
Action
mechanism: dual orexin receptor antagonist. As part of its drug discovery efforts on G-Protein Coupled Receptors, Actelion has built a library of potent dual oral orexin receptor antagonists (DORAs). These compounds are active on both OX1 and OX2, the receptors which mediate the actions of orexins. Orexins are neuropeptide modulators that act functionally at the interface of alertness, energy homeostasis and reward:aversion systems, essentially to regulate vigilance and alertness states. Defects of the orexin peptides, or their receptors, are associated with wakefulness and sleep disorders. The anatomical distribution of orexin receptors in the brain supports the essential role that orexin plays in promoting alertness and maintaining wakefulness under situations of high motivational relevance, e.g. circadian vigilance states, reward opportunities or exposure to threats. Orexins and their receptors are highly conserved across vertebrate species. Actelion's work with dual orexin receptor antagonism has demonstrated that blocking the activity of the orexin receptors offers the potential to restore normal physiological sleep. The company's new DORA is orally active, effectively crosses the blood-brain barrier and is currently evaluated as a treatment for insomnia.
Disease: insomnia
Therapeutic area: CNS diseases
Country:
Trial details:
Latest
news: * On July 7, 2016, Actelion announced that the company is initiating a Phase II program with its new dual orexin receptor antagonist (DORA) in patients with insomnia. The decision to move into a Phase II program is based on excellent data collected from the preclinical and Phase I clinical program, as well as a thorough understanding of the potential of dual orexin receptor antagonism on sleep efficacy and architecture. Information gathered on the optimal profile for a DORA has resulted in the discovery of a compound that demonstrates fast onset of CNS effects and natural physiologic sleep architecture in animal models. Data from an extensive Phase I program have confirmed the optimal pharmacokinetic and pharmacodynamic profile for a sleep medication, together with excellent safety and tolerability.
The Phase II program consists of two studies, one in adult and one in elderly patients. It is designed to evaluate the effect of Actelion's DORA versus placebo on sleep maintenance and sleep initiation, as well as next-day residual effect and next-day performance. The adult study will also include an active reference arm with zolpidem, as the most widely used insomnia treatment targeting GABA-A receptors. Both studies will also generate information on sleep architecture and sleep quality.
The first study is a multi-center, double-blind, randomized, placebo-controlled, active reference, parallel-group, dose-response study to evaluate the efficacy and safety of Actelion's DORA. The study is expected to commence enrollment in Q4 2016 and will recruit approximately 300 adult patients diagnosed with insomnia. The study will comprise 6 treatment arms: placebo; zolpidem; 5, 10, 25, and 50 mg of Actelion's DORA. Treatment duration is 4 weeks. The primary endpoint is wake-time after sleep onset (WASO) at day 1 & 2.
The second study is a multi-center, double-blind, randomized, placebo-controlled, crossover, dose-response study to evaluate the efficacy and safety of Actelion's DORA. The study is also expected to commence enrollment in Q4 2016 and will recruit approximately 50 elderly patients diagnosed with insomnia. The study has a 5-period crossover design with 5 treatment arms: placebo; 5, 10, 25 and 50 mg of Actelion's DORA. Treatment duration in each period is 2 days. The primary endpoint is WASO at day 1 & 2.
Secondary objectives of both studies include evaluation of Actelion's DORA versus placebo on latency to persistent sleep (LPS) as well as subjective latency to sleep onset (sLSO) and subjective WASO (sWASO). Safety and tolerability will also be evaluated.
