A Bridging Trial Comparing Sugammadex (Org 25969) at Reappearance of T2 in Japanese and Caucasian Participants. Part B: Caucasian Participants (P05971)

NCT00552617 | Completed Phase 2 Results

• 4 other identifiers: P0597119.4.208BMK-8616-0352005-001133-15
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of the trial was to establish the dose-response relation of sugammadex (Org 25969) given as a reversal agent of rocuronium or vecuronium at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control first twitch, T1) during sevoflurane anesthesia for Caucasian participants.

Conditions

Anesthesia, General

Outcome Measures

Primary Outcomes (1)

• Time From Start of Administration of Sugammadex or Placebo to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9

  Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB.

  Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.9 (up to 24 hours)

Secondary Outcomes (2)

• Time From Start of Administration of Sugammadex or Placebo to Recovery of the T4/T1 Ratio to 0.7

  Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.7 (up to 24 hours)

• Time From Start of Administration of Sugammadex or Placebo to Recovery of the T4/T1 Ratio to 0.8

  Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.8 (up to 24 hours)

Study Arms (10)

Rocuronium + Placebo

PLACEBO COMPARATOR

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Drug: Placebo; Drug: Rocuronium

Rocuronium + 0.5 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Rocuronium

Rocuronium + 1.0 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Rocuronium

Rocuronium + 2.0 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Rocuronium

Rocuronium + 4.0 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Rocuronium

Vecuronium + Placebo

PLACEBO COMPARATOR

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Drug: Placebo; Drug: Vecuronium

Vecuronium + 0.5 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Vecuronium

Vecuronium + 1.0 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Vecuronium

Vecuronium + 2.0 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Vecuronium

Vecuronium + 4.0 mg/kg Sugammadex

EXPERIMENTAL

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV.

Drug: Sugammadex; Drug: Vecuronium

Interventions

Sugammadex DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium. Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Also known as: Org 25969

Rocuronium + 0.5 mg/kg Sugammadex; Rocuronium + 1.0 mg/kg Sugammadex; Rocuronium + 2.0 mg/kg Sugammadex; Rocuronium + 4.0 mg/kg Sugammadex; Vecuronium + 0.5 mg/kg Sugammadex; Vecuronium + 1.0 mg/kg Sugammadex; Vecuronium + 2.0 mg/kg Sugammadex; Vecuronium + 4.0 mg/kg Sugammadex

Placebo DRUG

After induction of anesthesia an intubation dose of NMBA was administered IV: either 0.9 mg/kg rocuronium (arm 1) or 0.1 mg/kg vecuronium (arm 6). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of Placebo IV was administered

Rocuronium + Placebo; Vecuronium + Placebo

Rocuronium DRUG

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV. Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Rocuronium + 0.5 mg/kg Sugammadex; Rocuronium + 1.0 mg/kg Sugammadex; Rocuronium + 2.0 mg/kg Sugammadex; Rocuronium + 4.0 mg/kg Sugammadex; Rocuronium + Placebo

Vecuronium DRUG

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Vecuronium + 0.5 mg/kg Sugammadex; Vecuronium + 1.0 mg/kg Sugammadex; Vecuronium + 2.0 mg/kg Sugammadex; Vecuronium + 4.0 mg/kg Sugammadex; Vecuronium + Placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is of American Society of Anesthesiologists (ASA) class 1 - 3;
• Is at least 20 years but under 65 years of age;
• Caucasian participants;
• Is scheduled for elective surgery requiring muscle relaxation in supine position and under sevoflurane anesthesia with an anticipated duration of about 1.5-3 hours;
• Has given written informed consent.

You may not qualify if:

• Participants in whom a difficult intubation because of anatomical malformations was expected;
• Is known or suspected to have neuromuscular disorders impairing neuromuscular blocking (NMB) and/or significant renal dysfunction (for example a creatinine level \> 1.6 mg/dl) and/or severe hepatic dysfunction.
• Is known or suspected to have a (family) history of malignant hyperthermia;
• Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
• Is receiving medication expected to interfere with the rocuronium or vecuronium given in this trial, based on the dose and time of administration;
• Females who were pregnant;
• Females of childbearing potential not using birth control or using only oral contraception as birth control;
• Was breast-feeding;
• Has already participated in P05971, or in another trial with sugammadex;
• Has participated in another clinical trial, not preapproved by the Sponsor, within 6 months of entering into P05971.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Puhringer FK, Gordon M, Demeyer I, Sparr HJ, Ingimarsson J, Klarin B, van Duijnhoven W, Heeringa M. Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship. Br J Anaesth. 2010 Nov;105(5):610-9. doi: 10.1093/bja/aeq226. Epub 2010 Sep 28.

  PMID: 20876699 RESULT

Related Links

• Click here to access a synopsis of the study results.

MeSH Terms

Interventions

Sugammadex; Rocuronium; Vecuronium Bromide

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Androstanols; Androstanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2007
• First Posted: November 2, 2007
• Study Start: September 20, 2005
• Primary Completion: August 31, 2006
• Study Completion: August 31, 2006
• Last Updated: November 25, 2019
• Results First Posted: February 15, 2019

Record last verified: 2019-11