Remimazolam – anaesthetic/sedative

Remimazolam (CNS 7056) is a new short-acting sedative and general anaesthetic that acts on GABAA receptors. The substance was added to PAION's portfolio by acquiring CeNeS who in turn had acquired the substance from GlaxoSmithKline. Remimazolam is a water-soluble, rapid and short-acting GABAA receptor modulator interacting with the benzodiazepine site. After intravenous administration to human volunteers and patients, Remimazolam rapidly induces sedation. Importantly the sedative effects rapidly disappear after cessation of administration. The rapid offset of effect of the compound is due to its metabolism by esterase enzymes that are widely distributed throughout the body. Therefore it is anticipated that Remimazolam can be clinically developed as a sedative agent for day case procedures, the induction and maintenance of anaesthesia and as a sedative for mechanical ventilation in the Intensive Care Unit (ICU).

In 2007 CeNeS completed a license agreement for Remimazolam with Ono Pharmaceuticals. Under this agreement, Ono will develop and commercialize Remimazolam for the Japanese territory.

Since the start of the clinical development of Remimazolam in September 2008, PAION has performed two Phase I studies and two Phase II study:

1) A Phase I study (single dose) with volunteers undergoing endoscopy of the upper gastrointestinal tract;

2) A Phase Ib study (multiple dose) with volunteers undergoing a colonoscopy;

3) A Phase IIa study (single dose) with patients undergoing endoscopy of the upper gastrointestinal tract,

4) A Phase IIb study (multiple dose) with patients undergoing a colonoscopy.

The aim of the Phase IIb study was to further refine the optimal dose regimen for Phase III with a multi-centre trial