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LAS VEGAS -- Remimazolam, a short-acting benzodiazepine anesthetic drug in development for colonoscopy sedation, was effective with rapid onset and also rapid recovery in a trial comparing it both to placebo and to midazolam, a researcher said here.
In a multi-center, prospective, double-blind randomized control trial, remimazolam helped prepare patients sooner for colonoscopies and allowed them to recover faster after the surgery than placebo, reported , of Indiana University School of Medicine in Indianapolis, at the . The novel agent also worked better than midazolam given on an open-label basis. All patients in the trial received fentanyl.
The study's primary endpoint was a combination of three criteria: completion of colonoscopy, no requirement for an alternative sedative, and no requirement for more than five doses of study medication within any 15-minute period (or three doses of midazolam in any 12-minute interval).
This was met by 91.3% of the remimazolam group, compared to 1.7% for placebo and 25.2% for midazolam (P<0.0001). Remimazolam was also significantly superior to the other treatments for adequate sedation per protocol (93.9% remimazolam versus 26.7% placebo versus 45.6% midazolam, respectively) and no rescue medicine needed (96.6% versus 5.0% versus 35.3%, respectively).
Remimazolam is rapidly metabolized to an inactive metabolite by tissue esterases, rather than by hepatic cytochrome P450 enzymes, giving it a terminal elimination half-life of 45 minutes, Rex said. Midazolam, in contrast, does require P450 enzymes for elimination and its half-life is 4.3 hours.
Presumably as a result, time from end of procedure to regaining full alertness was 7.1 minutes with remimazolam versus 21.3 minutes for placebo and 15.7 minutes with midazolam (P<0.0001 versus midazolam).
Session moderator , of Mount Sinai Hospital in New York City, told 鶹ý that this finding is the most significant aspect of remimazolam.
"The big improvement is with the recovery time," said Greenwald, who was not involved with the study. When it takes longer for the drug to wear off, he explained,"[patients] are groggier and take longer to move out of the endoscopy suite."
By the same token, Greenwald said, a faster recovery often means "less problems after the procedure."
Patients receiving remimazolam experienced adverse events at a slightly lower rate overall than both placebo and midazolam patients (73.2% versus 78.3% placebo versus 90.3% midazolam, respectively; P=0.003), with hypotension and hypertension the most common adverse events seen in all three study groups. But rates of hypotension were significantly lower with remimazolam than with midazolam (44.3% versus 67.3%, P=0.0003).
Median age of the 461 patients was 55, with three-quarters white and slightly more than half female.
Rex explained that the open-label midazolam arm had been requested by the FDA, which wanted an active comparator as well as the blinded placebo control.
Paion, the drug's British sponsor, has big plans for remimazolam, "focusing all its [U.S.] business and financial resources on successfully completing its ongoing clinical development program in procedural sedation," according to a . The firm said it has also been developing the drug for general anesthesia and intensive care unit sedation.
Remimazolam could indeed also be used in general anesthesia, Rex told 鶹ý.
Paion said the study's comparisons with midazolam "will not be part of the label claims. They will however serve as valuable data to plan future studies and perform pharmacoeconomic modelling."
John Gever contributed to this report