Switzerland-based biopharmaceutical company Actelion Ltd 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 data collected from the preclinical and Phase I clinical program, as well as a thorough understanding of the potential of DORA 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 central nervous system 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.
Actelion CEO Jean-Paul Clozel, MD, says in a release: “Insomnia is not a lifestyle complaint, but a medical condition that can affect our physical, mental, and social health. Actelion has a rich experience with dual orexin receptor antagonism, which has demonstrated how this mechanism can restore natural sleep. Actelion’s drug discovery efforts have now resulted in a compound that could deliver on the potential that this mechanism offers. Our new DORA is an excellent example of how our innovative drug discovery is creating significant potential.”
The Phase II program will consist 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 fourth quarter of 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 fourth quarter 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.
Guy Braunstein, MD, head of global clinical development, says: “In a little over one year, we have evaluated this very promising compound in a Phase I program, which provided us with a wealth of data. The pharmacokinetic and pharmacodynamic profiles suggest that our compound offers an optimal combination of the desired effect on sleep and a low potential to impact next-day performance. The Phase II program should provide the data required to design a Phase III program to differentiate this new product.”
Martine Clozel, MD, chief scientific officer, says: “With our understanding of the potential that a dual orexin receptor antagonist has to offer, we have been very motivated to continue our drug discovery efforts. Taking into account what we have learned from our research and from available clinical data, we were able to define the optimal profile of a new DORA. Importantly, we were looking for a highly potent compound with a fast onset, and a duration of action which would not exceed a normal night’s sleep. With our robust selection criteria in place we believe we have created and selected the optimal compound to transform the way sleep disorders are treated.”