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

15 Citations (Scopus)

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 2013

Fingerprint

Colonoscopy
Volunteers
Flumazenil
Hypnotics and Sedatives
Fentanyl
Placebos
remimazolam
Benzodiazepines
Pharmaceutical Preparations
Hypotension
Cross-Over Studies
Healthy Volunteers
Arterial Pressure

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Medicine(all)

Cite this

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

A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy. / Worthington, Mark T.; Antonik, Laurie J.; Goldwater, D. Ronald; Lees, James P.; Wilhelm-Ogunbiyi, Karin; Borkett, Keith M.; Mitchell, Mack C.

In: Anesthesia and Analgesia, Vol. 117, No. 5, 11.2013, p. 1093-1100.

Research output: Contribution to journalArticle

Worthington, MT, Antonik, LJ, Goldwater, DR, Lees, JP, Wilhelm-Ogunbiyi, K, Borkett, KM & Mitchell, MC 2013, 'A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy', Anesthesia and Analgesia, vol. 117, no. 5, pp. 1093-1100. https://doi.org/10.1213/ANE.0b013e3182a705ae
Worthington MT, Antonik LJ, Goldwater DR, Lees JP, Wilhelm-Ogunbiyi K, Borkett KM et al. A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy. Anesthesia and Analgesia. 2013 Nov;117(5):1093-1100. https://doi.org/10.1213/ANE.0b013e3182a705ae
Worthington, Mark T. ; Antonik, Laurie J. ; Goldwater, D. Ronald ; Lees, James P. ; Wilhelm-Ogunbiyi, Karin ; Borkett, Keith M. ; Mitchell, Mack C. / A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy. In: Anesthesia and Analgesia. 2013 ; Vol. 117, No. 5. pp. 1093-1100.
@article{528f447213484451b5a55a7c3bb254af,
title = "A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy",
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.",
author = "Worthington, {Mark T.} and Antonik, {Laurie J.} and Goldwater, {D. Ronald} and Lees, {James P.} and Karin Wilhelm-Ogunbiyi and Borkett, {Keith M.} and Mitchell, {Mack C.}",
year = "2013",
month = "11",
doi = "10.1213/ANE.0b013e3182a705ae",
language = "English (US)",
volume = "117",
pages = "1093--1100",
journal = "Anesthesia and Analgesia",
issn = "0003-2999",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - A phase ib, dose-finding study of multiple doses of remimazolam (cns 7056) in volunteers undergoing colonoscopy

AU - Worthington, Mark T.

AU - Antonik, Laurie J.

AU - Goldwater, D. Ronald

AU - Lees, James P.

AU - Wilhelm-Ogunbiyi, Karin

AU - Borkett, Keith M.

AU - Mitchell, Mack C.

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84887070779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887070779&partnerID=8YFLogxK

U2 - 10.1213/ANE.0b013e3182a705ae

DO - 10.1213/ANE.0b013e3182a705ae

M3 - Article

C2 - 24108261

AN - SCOPUS:84887070779

VL - 117

SP - 1093

EP - 1100

JO - Anesthesia and Analgesia

JF - Anesthesia and Analgesia

SN - 0003-2999

IS - 5

ER -