A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy

Mark T. Worthington, Laurie J. Antonik, D. Ronald Goldwater, James P. Lees, Karin Wilhelm-Ogunbiyi, Keith M. Borkett, Mack C. Mitchell

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

BACKGROUND: We performed the first multiple dose study of remimazolam designed to assess both the feasibility of maintaining suitable sedation during colonoscopy and reversing the sedative effects of remimazolam with flumazenil. METHODS: Healthy volunteers received fentanyl followed by remimazolam for sedation during colonoscopy. Three dose groups of 15 volunteers each received remimazolam in increasing initial doses, plus top-up doses to maintain sedation for a 30-minute period. In a separate double-blind crossover part of the trial, 6 volunteers were sedated with a single high dose of remimazolam, followed by flumazenil or placebo to reverse the sedation. RESULTS: Successful sedation that was adequate for colonoscopy was achieved in >70% of subjects. After the procedure, subjects rapidly recovered to fully alert, with a median of <10 minutes overall. Failures were due to the inability to sedate or adverse events, with 1 subject failing due to hypotension (arterial blood pressure 80/40) and low Spo2 (<90%). There were no serious adverse events reported, and no events that were unexpected with the combination of a benzodiazepine and fentanyl. The study also showed that sedation was rapidly reversible (1.0 minutes flumazenil vs 10.5 minutes placebo) without resedation. CONCLUSIONS: Remimazolam has the attributes of a sedative drug, with success rates comparable with recent studies of other drugs. Remimazolam provided adequate sedation in 33 of 44 subjects undergoing colonoscopy, and its sedative effects were easily reversed with flumazenil.

Original languageEnglish (US)
Pages (from-to)1093-1100
Number of pages8
JournalAnesthesia and analgesia
Volume117
Issue number5
DOIs
StatePublished - Nov 1 2013

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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    Worthington, M. T., Antonik, L. J., Goldwater, D. R., Lees, J. P., Wilhelm-Ogunbiyi, K., Borkett, K. M., & Mitchell, M. C. (2013). A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy. Anesthesia and analgesia, 117(5), 1093-1100. https://doi.org/10.1213/ANE.0b013e3182a705ae