Date: 2017-06-28
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).
- Remimazolam is partnered in the U.S., Canada, China, Russia (CIS), Turkey, the MENA region, and South Korea with Cosmo Pharmaceuticals, Pharmascience (Pendopharm), Yichang Humanwell, R-Pharm, TR-Pharm, and Hana Pharm
respectively. For all other markets, remimazolam is available for licensing.
Disease: procedural sedation in patients undergoing bronchoscopy
Therapeutic
area: CNS diseases
Country: USA
Trial
details:
- This prospective, double-blind, randomized, placebo and active controlled, multi-center, parallel group study is comparing remimazolam to placebo, with an additional open label arm for midazolam, in patients undergoing a bronchoscopy. Patients will be randomized to receive Remimazolam, midazolam or placebo in addition to fentanyl to achieve moderate sedation. The primary endpoint is the successful completion of the bronchoscopy procedure with no requirement for an alternative sedative. (NCT02296892)
Latest
news:
- • On June 28, 2017, Paion announced that remimazolam met its primary efficacy endpoint in a pivotal U.S. Phase III
clinical trial in procedural sedation in patients undergoing bronchoscopy. This Phase III clinical trial has been conducted at 15 sites throughout the U.S. in 446 patients . In this trial 162 patients (37.6%) were ASA III patients (American Society of Anesthesiologists classification; ASA III: patients with severe systemic disease) and the average age of all patients was 62.3 years as compared to 6.6% ASA III patients and an average age of 54.9 years of all patients in the previously
reported pivotal Phase III colonoscopy trial. Patients were randomized to receive either remimazolam, midazolam, or placebo in combination with fentanyl for pain control in order to achieve adequate sedation to start and perform the procedure. In order to ensure the performance of the scheduled bronchoscopy, midazolam was available for all patients as rescue medication for non-responders. The primary outcome measure was a composite endpoint defined as: no need for rescue medication, completion of the procedure and no more than 5 doses within any 15-minute window for remimazolam/placebo and no more than 3 doses within any 12-minute window for midazolam. The primary endpoint was reached in 82.5% of the patients treated in the remimazolam arm and 3.4% in the placebo arm. Important secondary endpoints included median time from start of medication to start of procedure (5.0 minutes in the remimazolam arm versus 17.0 minutes for placebo) and median time from end of procedure to return to full alertness (remimazolam 6.0 minutes versus placebo 14.0 minutes).
Additionally, the patients’ subjective impression of time from last dose to “back to normal” was a median of 404 minutes for remimazolam versus 935 minutes for placebo.
- In the open label midazolam arm, procedural success was achieved in 34.8% of patients. Midazolam patients showed a median time from start of medication to start of procedure of 16.0 minutes and a median time from end of procedure to
return to full alertness of 12.0 minutes. Additionally, time from last dose to “back to normal” as reported by patients on midazolam was a median of 478.5 minutes.
- Overall adverse events, treatment-emergent adverse events and, in particular, incidents of hypotension and bradycardia occurred less frequently with remimazolam compared to midazolam. Hypotension was the most frequently reported adverse event occurring in 41.9% of patients treated with remimazolam, 62.7% with placebo and 49.3% with midazolam. Hypoxia occurred in 21.8% of patients given remimazolam, 20.3% in the placebo arm and 18.8% in the
midazolam arm. As expected, patients enrolled in this trial were of overall poorer health compared to those enrolled in the pivotal colonoscopy trial. Twenty-one patients across all treatment groups experienced a total of 26 treatment-emergent serious adverse events . Out of these 26 events, only two were considered related to treatment (remimazolam) and occurred in a single patient after administration of fentanyl at twice the dose allowed by the study protocol.
• On March 28, 2017, Paion announced the successful completion of patient recruitment in the pivotal U.S. Phase III clinical trial of remimazolam for procedural sedation in patients undergoing bronchoscopy. The trial is the second pivotal study of the remimazolam Phase III program
which was agreed upon between Paion and the FDA for the filing of remimazolam for market approval in the targeted indication procedural sedation. 446 patients undergoing bronchoscopy for diagnostic or therapeutic reasons have been included in this trial.
The randomized open-label midazolam study arm was added to generate data based on the labelled midazolam dose (U.S. label), including onset/offset times. It also served as an additional safety reference. Headline data are expected mid 2017.
- • On June 8, 2015, Paion announced the initiation of the second pivotal U.S. Phase III clinical trial of remimazolam for procedural sedation in patients undergoing bronchoscopy. The current trial forms the second pivotal study of the remimazolam Phase III program. Paion and the FDA have agreed on the remaining development program (indications, size of studies and design). This Phase III clinical trial is a prospective, double-blind, randomized, placeboand midazolam-controlled, U.S. multicenter study in 460 patients undergoing bronchoscopies. Patients will be randomized to receive Remimazolam, midazolam or placebo in addition to fentanyl to achieve moderate sedation. The primary endpoint is the successful completion of the bronchoscopy procedure with no requirement for an alternative sedative. The completion of patient recruitment is expected in 2016. Last March, Paion has already initiated a U.S. phase III clinical trial of remimazolam for procedural sedation in patients undergoing colonoscopy.
Is
general: Yes
