Dose-Finding Trial With Sugammadex Administered at 3 and 15 Minutes After 1.0 and 1.2 mg/kg Rocuronium Bromide in Participants of ASA Class 1-3 (P05944; MK-8616-024)

NCT00535743 | Completed Phase 2 Results

• 3 other identifiers: P0594419.4.206MK-8616-024
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this trial was to explore the dose-response relation of sugammadex (Org 25969; MK-8616) administered for the reversal of neuromuscular blockade (NMB) at 3 and 15 minutes following administration of 1.0 and 1.2 mg/kg of Esmeron® (rocuronium) in participants receiving surgery, classified as American Society of Anesthesiologists (ASA) class 1 (otherwise normal, healthy participant), class 2 (participant with mild systemic disease), or class 3 (participant with a severe systemic disease that limits activity, but is not incapacitating).

Conditions

Anesthesia, General

Outcome Measures

Primary Outcomes (1)

• Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9

  Mean time from start of study treatment administration to recovery of participant T4/T1 ratio to 0.9 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.9 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).

  Up to 240 minutes following administration of study treatment

Secondary Outcomes (3)

• Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.8

  Up to 200 minutes following administration of study treatment

• Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.7

  Up to 180 minutes following administration of study treatment

• Number of Participants Experiencing an Adverse Event

  Up to 7 days following administration of study treatment

Study Arms (24)

Arm A. Placebo; 3 min after 1 mg/kg Esmeron®

PLACEBO COMPARATOR

Placebo (single intravenous (IV) bolus) administered 3 minutes (min) after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Placebo; Drug: Esmeron®

Arm B. 2 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm C. 4 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm D. 8 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm E. 12 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm F. 16 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm G. Placebo; 15 min after 1 mg/kg Esmeron®

PLACEBO COMPARATOR

Placebo (single intravenous (IV) bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Placebo; Drug: Esmeron®

Arm H. 2 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm I. 4 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm J. 8 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm K. 12 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm L. 16 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm M. Placebo; 3 min after 1.2 mg/kg Esmeron®

PLACEBO COMPARATOR

Placebo (single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Placebo; Drug: Esmeron®

Arm N. 2 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm O. 4 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm P. 8 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm Q. 12 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm R. 16 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm S. Placebo; 15 min after 1.2 mg/kg Esmeron®

PLACEBO COMPARATOR

Placebo (single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Placebo; Drug: Esmeron®

Arm T. 2 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm U. 4 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm V. 8 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm W. 12 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Arm X. 16 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

EXPERIMENTAL

Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.

Drug: Sugammadex; Drug: Esmeron®

Interventions

Sugammadex DRUG

Sugammadex administered as a fast IV bolus dose (within 30 seconds) at 3 or 15 minutes following administration of Esmeron®, dosed at 2, 4, 8, 12 or 16 mg/kg according to participant actual body weight.

Also known as: Org 25969, MK-8616, BRIDION®

Arm B. 2 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm C. 4 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm D. 8 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm E. 12 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm F. 16 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm H. 2 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm I. 4 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm J. 8 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm K. 12 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm L. 16 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm N. 2 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm O. 4 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm P. 8 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm Q. 12 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm R. 16 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm T. 2 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm U. 4 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm V. 8 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm W. 12 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm X. 16 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

Placebo DRUG

0.9% NaCl administered as a fast IV bolus dose (within 30 seconds) at 3 or 15 minutes following administration of Esmeron®,

Also known as: NaCl 0.9%

Arm A. Placebo; 3 min after 1 mg/kg Esmeron®; Arm G. Placebo; 15 min after 1 mg/kg Esmeron®; Arm M. Placebo; 3 min after 1.2 mg/kg Esmeron®; Arm S. Placebo; 15 min after 1.2 mg/kg Esmeron®

Esmeron® DRUG

Esmeron® administered at 1 or 1.2 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.

Also known as: Zemuron®, Rocuronium bromide

Arm A. Placebo; 3 min after 1 mg/kg Esmeron®; Arm B. 2 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm C. 4 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm D. 8 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm E. 12 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm F. 16 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®; Arm G. Placebo; 15 min after 1 mg/kg Esmeron®; Arm H. 2 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm I. 4 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm J. 8 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm K. 12 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm L. 16 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®; Arm M. Placebo; 3 min after 1.2 mg/kg Esmeron®; Arm N. 2 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm O. 4 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm P. 8 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm Q. 12 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm R. 16 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®; Arm S. Placebo; 15 min after 1.2 mg/kg Esmeron®; Arm T. 2 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm U. 4 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm V. 8 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm W. 12 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®; Arm X. 16 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®

Eligibility Criteria

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

You may qualify if:

• Participants of ASA class 1 - 3, above or equal to the age of 18 years;
• Participants scheduled for surgical procedures with an anticipated duration of anesthesia of at least 120 minutes, without further need for muscle relaxation other than for intubation;
• Participants scheduled for surgical procedures in supine position;
• Participants who had given written informed consent.

You may not qualify if:

• Participants in whom a difficult intubation because of anatomical malformations was expected;
• Participants known or suspected to have neuromuscular disorders impairing neuromuscular blocking and/or significant renal dysfunction;
• Participants known or suspected to have a (family) history of malignant hyperthermia;
• Participants known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
• Participants receiving medication known to interfere with neuromuscular blocking agents, such as anticonvulsants and Mg\^2+;
• Participants who had already participated in this trial;
• Participants who had participated in another clinical trial, not pre-approved by the Sponsor, within 30 days of entering into this trial;
• Female participants who were pregnant: in females, pregnancy was to be excluded both from medical history and by a human chorionic gonadotropin (hCG) test within 24 hours before surgery except in females who were not of childbearing potential, i.e. at least 2 years menopausal or who had undergone tubal ligation or an hysterectomy;
• Female participants of childbearing potential not using any of the following methods of birth control (for one month): condom or diaphragm with spermicide, vasectomized partner (\>6 months), intrauterine device (IUD), abstinence;
• Female participants who were breast-feeding.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Puhringer FK, Rex C, Sielenkamper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology. 2008 Aug;109(2):188-97. doi: 10.1097/ALN.0b013e31817f5bc7.

  PMID: 18648227 DERIVED

MeSH Terms

Interventions

Sugammadex; Sodium Chloride; Rocuronium

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; 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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2007
• First Posted: September 26, 2007
• Study Start: March 4, 2004
• Primary Completion: July 20, 2004
• Study Completion: July 20, 2004
• Last Updated: February 11, 2019
• Results First Posted: February 11, 2019

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share