Date: 2014-02-11
Type of
information: Results
phase: 2
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: general anaesthesia in cardiovascular surgery
Therapeutic
area: CNS diseases - Cardiovascular diseases
Country: Germany
Trial
details:
- The Phase II study is a randomized, propofol and sevoflurane (standard treatment) controlled phase II study to evaluate the efficacy, safety and pharmacokinetics of remimazolam during general anaesthesia in cardiac surgery patients. After surgery a follow up sedation in the recovery room or the ICU for up to 24 h will take place. A total of 90 patients will be treated. The study is carried out at the Heart Center Leipzig. The study is designed to provide detailed information about the cardiovascular safety profile of remimazolam as an anaesthetic during general anaesthesia for cardiac surgery. Furthermore it is expected to deliver clear insights on early and predictable offset of its effect as well as easy titration of sedation in the postoperative phase.
Two doses of Remimazolam (6 mg/kg/h and 12 mg/kg/h) have been evaluated against each other and against propofol during induction of general anaesthesia. In the maintenance phase of anaesthesia Remimazolam was tested against the combination of propofol and sevoflurane. Furthermore data in the postoperative sedation phase in the postoperative care unit or ICU against Propofol were obtained and can be used for further exploration of the ICU sedation indication. The study was designed such that the data can complement the anaesthesia study data conducted by Ono in Japan and could then be used together with the Japanese studies for filing.
Latest
news:
- • On May 28, 2014, Paion announced positive headline data from the Phase II clinical trial in Germany with the short-acting anaesthetic/sedative remimazolam in the EU lead indication "general anaesthesia" in patients undergoing major cardiac surgery with extracorporeal circulation. The primary efficacy endpoint of effectiveness as a general anaesthetic (defined as successful anaesthesia not requiring rescue therapy) was achieved in 98% of patients in the two Remimazolam dose groups and 96% in the Propofol/Sevoflurane group. Therefore, an excellent efficacy rate across all treatment groups was shown. As expected, the onset and offset of action profile was comparable between all treatment groups, showing that Remimazolam indeed shares the fast-acting sedative profile of Propofol. The safety profile was generally very good in all treatment groups. One of the key targets of this trial was to assess the cardiostability during cardiac surgery with Remimazolam when compared to Propofol/Sevoflurane, both of which are known to cause cardiac depression. The study evaluated a substantial number of parameters to analyse these effects. Remimazolam already had shown excellent cardiostability in the ONO Phase III study. During cardiac surgery norepinephrine is routinely used to maintain blood pressure in the normal range and counteract pronounced blood pressure decreases. Norepinephrine and other adrenergic substances however are known to impair the microcirculation in vital organs and thus have a negative effect on short, mid and long-term outcomes. Therefore lowering the norepinephrine dose is of high medical relevance. The amount of norepinephrine required to counteract the cardio-depressive effects (e.g., drop in blood pressure) is a direct measure of the cardio-depressive effects in each group: a higher amount of norepinephrine would be used to counteract higher cardio-depressive effects. The use of norepinephrine was 36.7% lower in Remimazolam treated patients when compared to the Propofol/Sevoflurane group which can be regarded as a clinically meaningful differentiation. Dr Wolfgang Söhngen, CEO of Paion, commented: "This trial was designed to bridge the European anaesthesia program to the Japanese data set which has been successfully achieved. Within the next months, this will be complemented by the PK data, which is still work in progress. We are currently in advanced stages of preparing the EU Phase III program including the EMA advice meeting to fine-tune the development program on the basis of the scientific advice meeting with the BfArM in 2013l."
- • On February 11, 2014, Paion has announced the successful completion of the recruitment of the Phase II clinical trial with the short-acting anaesthetic/sedative remimazolam in the indication 'anaesthesia' in patients undergoing cardiac surgery. No drug-related Serious Adverse Event has been reported.The Phase II study was a randomized, propofol and sevoflurane (standard treatment) controlled Phase II study to evaluate the efficacy, tolerability and pharmacokinetics of remimazolam during general anaesthesia in patients undergoing cardiac surgery using a heart-lung machine. After surgery a follow up sedation in the recovery room or in the intensive care unit (ICU) for up to 24 h has taken place. A total of 90 patients have been treated. Results of the study are still expected in the first half of 2014. Dr. Wolfgang Söhngen, CEO of PAION, commented: ' We will now carefully analyze the data package in order to use the data obtained for the scientific advice meeting with the European regulatory authority (EMA) to prepare the European Phase III trial.
- • On September 9, 2013, Paion has announced the start of a Phase II clinical trial with the short-acting anaesthetic/sedative remimazolam in the indication 'anaesthesia' in patients undergoing cardiac surgery. Results of the study are expected in the first half of 2014. The aim of the concept is to restore the patient as quickly as possible i.e. a rapid weaning from mechanical ventilation (extubation) within 6 hours after surgery. This concept provides a significant clinical and health economic benefit through shortening extubation times after surgery leading to better patient outcomes, reduced stay on the ICU and in the hospital. The aim is to establish remimazolam as a key component of this approach. The study was designed such that the data can be compared with the anaesthesia study conducted by Ono in Japan.
- • On August 5, 2013, the German biopharmaceutical company Paion has announced that the BfArM, the German regulatory authority has granted approval for the Phase II clinical trial with the short-acting anaesthetic/sedative remimazolam in the indication 'anaesthesia' in cardiovascular surgery. Currently, final preparations for the official start of the study are ongoing.
- • On March 6, 2013, Paion has announced that it is about to initiate a late-stage European program with the short-acting anesthetic/sedative, remimazolam, in general anaesthesia. In May 2012, remimazolam has successfully completed a Phase II trial in general anaesthesia in Japan. A Phase II/III trial of remimazolam in general anesthesia was also started by Paion's collaboration partner, ONO, in November 2012. Paion has now announced that it is in advanced preparation to conduct a Phase II trial with remimazolam, in general anaesthesia in cardiovascular surgery in the 2nd half of 2013.
- In February 2013, the company held a formal scientific advice meeting with the German regulatory authority on the European clinical development program for remimazolam in general anaesthesia. Pending the outcome of the planned and ongoing trials, Paion assumes that a single Phase II and a single Phase III trial in general anaesthesia in addition to the Japanese Phase II/III trial will be sufficient for EU approval. In preparation for the European Phase III trial, further scientific advice meetings are planned with European regulatory authorities. Paion expects to conduct this trial in 2014.
- Remimazolam is available for licensing outside Japan and China, where the compound is partnered with Ono Pharmaceutical and Yichang Humanwell, respectively.
Is
general: Yes
