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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).

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ClinicalTrials.gov Identifier: NCT03519854
Recruitment Status : Completed
First Posted : May 9, 2018
Results First Posted : February 1, 2019
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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®.

Condition or disease Intervention/treatment Phase
Neuromuscular Blockade Drug: Placebo Drug: Sugammadex Drug: Esmeron® Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 1, 2002
Actual Primary Completion Date : June 1, 2003
Actual Study Completion Date : June 1, 2003

Resource links provided by the National Library of Medicine


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 Name: 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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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 Name: 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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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 Name: 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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide

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: Sugammadex
Sugammadex administered as a fast IV bolus dose (within 30 seconds), dosed according to participant actual body weight.
Other Name: Org 25969; MK-8616; Bridion®.

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 Name: Rocuronium bromide




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



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Layout table for eligibility information
Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03519854


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03519854     History of Changes
Other Study ID Numbers: P05940
MK-8616-020 ( Other Identifier: Merck Protocol Number )
19.4.202 ( Other Identifier: Organon Protocol Number )
First Posted: May 9, 2018    Key Record Dates
Results First Posted: February 1, 2019
Last Update Posted: April 2, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
Layout table for MeSH terms
Rocuronium
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs