Clinical Trials

Date: 2017-03-27

Type of information: Results

phase: 3

Announcement: results

Company: Paion (Germany)

Product: remimazolam

Action mechanism:

• benzodiazepine derivative. Remimazolam is a short-acting general anaesthetic/sedative. Sedatives are used, for example, in endoscopic procedures such as colonoscopies. After intravenous administration remimazolam rapidly induces the desired sedation. Importantly, this sedative effect quickly disappears. This rapid offset of the effect of the substance is due to its metabolism by tissue esterase enzymes that are widely distributed throughout the body. Remimazolam is being developed as a sedative agent for day case procedures (procedural sedation) as well as for the induction and maintenance of anaesthesia. It could also be used as a sedative for patients in the Intensive Care Unit (ICU).

Disease: procedural sedation in patients undergoing colonoscopy

Therapeutic area: CNS diseases

Country: USA

Trial details:

• This Phase III trial is part of the U.S. development program agreed upon between Paion and the FDA for the filing of remimazolam for market approval in the targeted indication procedural sedation. This prospective, double-blind, randomized, placebo- and active controlled, multicenter, parallel group study enrolled 79 high-risk patients (i.e. ASA III/IV) undergoing a colonoscopy into a remimazolam, midazolam or placebo (including midazolam ‘rescue’ sedation) treatment group. The disposition for ASA III and IV were equally distributed for the remimazolam and control patients. The primary objective was to assess the safety of multiple doses (initial dose and additional top-up doses) of remimazolam compared to placebo and midazolam, following administration of a standard dose of fentanyl. The fentanyl, remimazolam and midazolam doses were reduced compared to the pivotal U.S. Phase III trials as indicated in the label for midazolam which Paion is targeting for remimazolam.

Latest news:

• • On March 27, 2017 , Paion announced that remimazolam appeared safe in a study comparing remimazolam sedation to placebo with midazolam rescue in high risk (ASA III/IV) patients (American Society of Anesthesiologists classification; ASA III: patients with severe systemic disease, ASA IV: patients with severe systemic disease that is a constant threat to life) undergoing colonoscopy. In addition the efficacy and efficiency gains were comparable to the first pivotal U.S. Phase III trial in colonoscopy patients. As ASA III/IV patients can develop symptoms that require immediate stabilizing interventions, these patients are mostly treated in a hospital environment. The classification of the patients’ ASA status was checked by an external anesthesiologist who was not otherwise involved in the trial. Remimazolam demonstrated good respiratory and cardiovascular stability as compared to placebo with midazolam rescue. No adverse events of concern were observed in either group. There were several additional outcome measures included to assess efficacy: One such outcome was a composite endpoint, composed of success of the procedure, no need for rescue medication, and completion of the procedure with no more than 5 doses given within any 15-minute interval. This endpoint was achieved in 84.4% of the patients in the remimazolam arm and 0% in the placebo arm. Further relevant endpoints for remimazolam showed a median time from start of medication to start of procedure of 5.0 minutes (placebo 18.5 minutes) and a median time from end of procedure to return to full alertness of 3.0 minutes (placebo 5.0 minutes).
• This study also included an open label arm in which midazolam was dosed according to U.S. label. Success of the procedure was achieved in 12.9% of the midazolam patients. Midazolam patients showed a median time from start of medication to start of procedure of 19.0 minutes and a median time from end of procedure to return to full alertness of 7.0 minutes.
• • On December 1, 2015, Paion announced the initiation of a smaller dedicated safety study of remimazolam in ASA III/IV patients (American Society of Anesthesiologists classification III to IV) undergoing colonoscopy as part of the U.S. Phase III program. This trial will run alongside the two ongoing pivotal U.S. Phase III trials in colonoscopy and bronchoscopy. The trial is part of the development program, which Paion and the FDA agreed upon for the filing of remimazolam in the targeted indication ‘procedural sedation’. This prospective, double-blind, randomized, placebo- and active controlled, multicenter, parallel group study involves about 75 high-risk patients (i.e. ASA III/IV) undergoing a colonoscopy with remimazolam compared to midazolam and placebo . Completion of patient recruitment is expected in 2016.

Is general: Yes