Efficacy, Safety and Pharmacokinetics of Sugammadex (Org 25969; MK-8616) at 3 Different Time Points After 0.6 mg/kg Esmeron® in Male Participants (P05940; MK-8616-020).

March 19, 2019 updated by: Merck Sharp & Dohme LLC

A Multi-center, Randomized, Assessor-blinded, Placebo Controlled, Phase II, Parallel Dose-finding Trial in Male Subjects of ASA 1-2 to Assess the Efficacy, Safety and Pharmacokinetics of 5 Doses of Org 25969 When Administered After 0.6 mg.Kg-1 Esmeron® at 3, 5 or 15 Minutes

This study investigates the efficacy, safety, and pharmacokinetics of sugammadex (Org 25969; MK-8616) when administered for the reversal of neuromuscular blockade in male participants receiving surgery, classified as American Society of Anesthesiologists (ASA) class 1 (otherwise normal, healthy participant) to class 2 (participant with mild systemic disease). The primary objective of this study is to explore the dose-response relation of sugammadex given as a reversal agent at 3, 5, or 15 minutes following administration of 0.6 mg/kg Esmeron®.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Participants of ASA class 1 to 2.
  • Participants scheduled for surgical procedures with an anticipated duration of anesthesia of at least 75 minutes, without further need for muscle relaxation other than for intubation.

Exclusion Criteria:

  • Participants in whom a difficult intubation because of anatomical malformations is expected.
  • Participants known or suspected to have neuromuscular disorders and/or significant hepatic or 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, aminoglycosides, and Mg^2+.
  • Participants who have already participated in this trial.
  • Participants who have participated in another clinical trial, not pre-approved by NV Organon, within 30 days of entering into this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Arm A. Placebo; given 3 minutes after Esmeron®
Placebo (single intravenous (IV) bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Placebo
0.9% NaCl administered as a fast IV bolus dose (within 30 seconds).
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Experimental: Arm B. 1 mg/kg Sugammadex; given 3 minutes after Esmeron®
Sugammadex (1 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm C. 2 mg/kg Sugammadex; given 3 minutes after Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm D. 4 mg/kg Sugammadex; given 3 minutes after Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm E. 6 mg/kg Sugammadex; given 3 minutes after Esmeron®
Sugammadex (6 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm F. 8 mg/kg Sugammadex; given 3 minutes after Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Placebo Comparator: Arm G. Placebo; given 5 minutes after Esmeron®
Placebo (single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Placebo
0.9% NaCl administered as a fast IV bolus dose (within 30 seconds).
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Experimental: Arm H. 1 mg/kg Sugammadex; given 5 minutes after Esmeron®
Sugammadex (1 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm I. 2 mg/kg Sugammadex; given 5 minutes after Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm J. 4 mg/kg Sugammadex; given 5 minutes after Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm K. 6 mg/kg Sugammadex; given 5 minutes after Esmeron®
Sugammadex (6 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm L. 8 mg/kg Sugammadex; given 5 minutes after Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Placebo Comparator: Arm M. Placebo; given 15 minutes after Esmeron®
Placebo (single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Placebo
0.9% NaCl administered as a fast IV bolus dose (within 30 seconds).
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Experimental: Arm N. 1 mg/kg Sugammadex; given 15 minutes after Esmeron®
Sugammadex (1 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm O. 2 mg/kg Sugammadex; given 15 minutes after Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm P. 4 mg/kg Sugammadex; given 15 minutes after Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm Q. 6 mg/kg Sugammadex; given 15 minutes after Esmeron®
Sugammadex (6 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.
Experimental: Arm R. 8 mg/kg Sugammadex; given 15 minutes after Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Drug: Esmeron®
Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight.
Other Names:
  • Rocuronium bromide
Drug: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Names:
  • Org 25969; MK-8616; Bridion®.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9
Time Frame: Up to 70 minutes following administration of study treatment
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 70 minutes following administration of study treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Heart Rate at Baseline
Time Frame: Up to 45 minutes prior to study treatment administration
Mean heart rate at baseline was assessed. Baseline heart rate was defined as the heart rate measured under stable anesthesia prior to administration of study treatment.
Up to 45 minutes prior to study treatment administration
Mean Heart Rate at 2 Minutes Following Administration of Study Treatment
Time Frame: 2 minutes following administration of study treatment
Mean heart rate at 2 minutes following administration of study treatment was assessed.
2 minutes following administration of study treatment
Mean Heart Rate at 30 Minutes Following Administration of Study Treatment
Time Frame: 30 minutes following administration of study treatment
Mean heart rate at 30 minutes following administration of study treatment was assessed.
30 minutes following administration of study treatment
Mean Corrected QT Interval (QTc) at Baseline
Time Frame: Up to 45 minutes prior to study treatment administration
Mean QTc interval at baseline was assessed. Baseline QTc interval was defined as the QTc interval measured under stable anesthesia prior to administration of study treatment. The baseline QTc interval is corrected for participant heart rate at baseline prior to study treatment administration using Fridericia's correction, where QTc = QT interval/(RR interval)^(1/3). RR interval = 60/heart rate.
Up to 45 minutes prior to study treatment administration
Mean Corrected QT Interval (QTc) at 2 Minutes Following Administration of Study Treatment
Time Frame: 2 minutes following administration of study treatment
Mean QTc interval at 2 minutes following administration of study treatment was assessed. The QTc interval is corrected for participant heart rate at 2 minutes following study treatment administration using Fridericia's correction, where QTc = QT interval/(RR interval)^(1/3). RR interval = 60/heart rate.
2 minutes following administration of study treatment
Mean Corrected QT Interval (QTc) at 30 Minutes Following Administration of Study Treatment
Time Frame: 30 minutes following administration of study treatment
Mean QTc interval at 30 minutes following administration of study treatment was assessed. The QTc interval is corrected for participant heart rate at 30 minutes following study treatment administration using Fridericia's correction, where QTc = QT interval/(RR interval)^(1/3). RR interval = 60/heart rate.
30 minutes following administration of study treatment
Number of Participants Experiencing an Adverse Event
Time Frame: Up to 7 days following administration of study treatment
The number of participants experiencing an adverse event (AE) was assessed. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product.
Up to 7 days following administration of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2002

Primary Completion (Actual)

June 1, 2003

Study Completion (Actual)

June 1, 2003

Study Registration Dates

First Submitted

May 8, 2018

First Submitted That Met QC Criteria

May 8, 2018

First Posted (Actual)

May 9, 2018

Study Record Updates

Last Update Posted (Actual)

April 2, 2019

Last Update Submitted That Met QC Criteria

March 19, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P05940
  • MK-8616-020 (Other Identifier: Merck Protocol Number)
  • 19.4.202 (Other Identifier: Organon Protocol Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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