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)

NCT ID: NCT00535743

Last Updated: 2019-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-04
• Study Completion Date: 2004-07-20

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).

Detailed Description

In the United States, the highest dose recommended in the package insert of Zemuron® (i.e. the trade name for Esmeron® in the US) is 1.2 mg/kg whereas in Europe it is 1.0 mg/kg. For both doses, dose recommendations for reversal with sugammadex were to be found. Hence, the present trial was set up to explore the dose-response relation of sugammadex given as an NMB reversal agent at 3 and 15 minutes following administration of 1.0 and 1.2 mg/kg of Esmeron® in subjects of ASA 1 to 3. The sub-investigator who performed any subjective safety assessments after anesthesia was to be remained blinded.

Conditions

Anesthesia, General

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: 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.

Esmeron®

Intervention Type: 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.

Interventions

Sugammadex

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Esmeron®

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

Intervention Type: DRUG

Other Intervention Names

Org 25969; MK-8616; BRIDION®; NaCl 0.9%; Zemuron®; Rocuronium bromide

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 18648227 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

19.4.206

Identifier Type: OTHER

Identifier Source: secondary_id

MK-8616-024

Identifier Type: OTHER

Identifier Source: secondary_id

P05944

Identifier Type: -

Identifier Source: org_study_id