AACHEN, Germany--(BUSINESS WIRE)--PAION AG, a specialty pharma company (ISIN DE000A0B65S3; Frankfurt Stock Exchange Prime Standard: PA8) today announces that data on the clinical results of remimazolam's U.S. Phase III colonoscopy trial were presented in the Colon/Stomach oral session at the 2016 American College of Gastroenterology (ACG) Annual Scientific Meeting in Las Vegas. Remimazolam is an innovative, ultra-short-acting benzodiazepine anesthetic/sedative for which positive topline data from this trial were published in June 2016.
Douglas Rex, M.D., Indiana University, Indianapolis, IN, U.S., principal investigator of this Phase III trial, presented the results.
The Phase III trial enrolled a total of 461 patients at 13 U.S. sites and was designed to evaluate the efficacy and safety of remimazolam compared to placebo (with midazolam rescue) in patients undergoing proceduralist- administered sedation for colonoscopy.
The primary outcome measure was a composite endpoint defined as: no need for rescue medication, completion of the procedure and no more than 5 top- up doses within any 15-minute window. The primary endpoint was reached in 91.3% of the patients in the remimazolam arm and 1.7% in the placebo (including midazolam rescue) arm. Important secondary endpoints in the remimazolam arm showed a median time from start of medication to start of procedure of 4.0 minutes (placebo 19.5 minutes) and a mean time from end of procedure to return to full alertness of 7.2 minutes (placebo 21.3 minutes). Additionally, time to "back to normal" as reported by patients on remimazolam was 331 minutes (placebo 572 minutes).
There were no treatment-emergent serious adverse events in the trial. Hypotension was 44.3% with remimazolam and 47.5% with placebo and accounted for most of the adverse events in all study arms. Hypoxia occurred in 1.0% of patients given remimazolam, 3.4% in the placebo arm.
On the Hopkins Verbal Learning Test administered five minutes after reaching the fully alert status, the total raw score, delayed recall, memory retention, and recognition discrimination scores were all better with remimazolam compared to placebo.
Patient satisfaction was similar in all arms of the study.
In addition to the detailed analysis of the primary and secondary endpoints of the Phase III trial (comparison to placebo), Dr. Rex also presented data for the open label midazolam arm. These results will not be part of the label claims. They will however serve as valuable data to plan future studies and perform pharmacoeconomic modelling. Midazolam patients showed a median time from start of medication to start of procedure of 19.0 minutes and a mean time from end of procedure to return to full alertness of 15.7 minutes. Midazolam patients took 553 minutes to be back to normal.
Hypotension was 67.3% with midazolam and hypoxia occurred in 1.0% of patients given midazolam.
Overview procedural results:
|Use of rescue sedation||3.40%||95.00%||64.70%|
|Average fentanyl dose||88.9 mcg||121.3 mcg||106.9 mcg|
|Start of medication to start of procedure (median)||4.0 minutes||19.5 minutes||19.0 minutes|
End of procedure to fully alert (mean)
|7.2 minutes||21.3 minutes||15.7 minutes|
|Mean time 1st dose to discharge||58 minutes||86 minutes||75 minutes|
Dr. Rex concluded: "Remimazolam, given under supervision of an endoscopist, appears to be safe and effective for procedural sedation in colonoscopy based on the results from this Phase III study. We saw significant differences in onset and recovery times as well as restoration of cognitive function and fewer adverse events when compared to midazolam or placebo. In addition, the need for fentanyl was lowest in the remimazolam group. If these data could be translated into medical practice, this would result in a meaningful gain in efficiency and patient comfort, which are important to achieve our goal to increase the overall colonoscopy screening rate."
Remimazolam is an ultra-short-acting intravenous benzodiazepine sedative/anesthetic, currently in Phase III clinical development for procedural sedation in the U.S. The first of two pivotal Phase III studies was completed successfully and reached its primary endpoint. In the human body, remimazolam is rapidly metabolized to an inactive metabolite by tissue esterases and not metabolized by cytochrome-dependent hepatic pathways. Like other benzodiazepines, remimazolam can be reversed with flumazenil to rapidly terminate sedation and anesthesia if necessary.
In clinical studies, remimazolam demonstrated efficacy and safety in over 1,000 patients. Data so far indicate that remimazolam has a rapid onset and offset of action combined with a favorable cardio-respiratory safety profile.
A pediatric development plan has been agreed with the FDA and will be implemented by Cosmo following completion of current development of remimazolam for adult patients. A full clinical development program for general anesthesia has been completed in Japan, and a Phase II study in general anesthesia has been completed in the E.U. Based on the positive results of the Phase II study in Japan, development for ICU sedation beyond 24 hours is considered following successful completion of development in procedural sedation and general anesthesia.
Remimazolam is partnered in the U.S., Canada, China, Russia (CIS), Turkey, the MENA region, and South Korea with Cosmo, Pharmascience (Pendopharm), Yichang Humanwell, R-Pharm, TR-Pharm, and Hana Pharm, respectively. For all other markets, remimazolam is available for licensing.
PAION AG is a publicly listed specialty pharmaceutical company developing and aiming to commercialize innovative drugs to be used in out-patient and hospital-based sedation, anesthesia and critical care services. PAION's lead compound is remimazolam, an intravenous, ultra-short-acting and controllable benzodiazepine sedative/anesthetic drug candidate. Currently, remimazolam is in active Phase III clinical development for use in procedural sedation in the U.S., where PAION is focusing all its business and financial resources on successfully completing its ongoing clinical development program in procedural sedation. Outside the U.S., PAION has so far focused on the development of remimazolam in the indication general anesthesia. Development of remimazolam in the indication intensive care unit (ICU) sedation is also part of the longer term life-cycle plan for remimazolam.
PAION is headquartered in Aachen (Germany) with further sites in Cambridge (United Kingdom) and New Jersey (USA).
PAION's vision is to become an acknowledged "PAIONeer" in sedation and anesthesia.
This release contains certain forward-looking statements concerning the future business of PAION AG. These forward-looking statements contained herein are based on the current expectations, estimates and projections of PAION AG's management as of the date of this release. They are subject to a number of assumptions and involve known and unknown risks, uncertainties and other factors. Should actual conditions differ from the Company's assumptions, actual results and actions may differ materially from any future results and developments expressed or implied by such forward- looking statements. Considering the risks, uncertainties and other factors involved, recipients should not rely unreasonably upon these forward- looking statements. PAION AG has no obligation to periodically update any such forward-looking statements to reflect future events or developments.
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