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).

Phase 2

Completed

• Conditions: Neuromuscular Blockade
• Interventions: Drug: Placebo; Drug: Sugammadex; Drug: Esmeron®

• Registration Number: NCT03519854
• Lead Sponsor: Merck Sharp & Dohme LLC

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®.

Detailed Description

Not available

Study Timeline

• Study Start: 2002-12-01
• Primary Completion: 2003-06-01
• Study Completion: 2003-06-01
• Study First Submitted: 2018-05-08
• Study First Submitted QC: 2018-05-08
• Study First Posted: 2018-05-09
• Results First Submitted: 2018-08-28
• Results First Submitted QC: 2018-08-28
• Results First Posted: 2019-02-01
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-19
• Last Update Posted: 2019-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 99

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm G. Placebo; given 5 minutes after Esmeron®	Placebo	Placebo (single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm G. Placebo; given 5 minutes after Esmeron®	Esmeron®	Placebo (single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm H. 1 mg/kg Sugammadex; given 5 minutes after Esmeron®	Esmeron®	Sugammadex (1 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm I. 2 mg/kg Sugammadex; given 5 minutes after Esmeron®	Sugammadex	Sugammadex (2 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm A. Placebo; given 3 minutes after Esmeron®	Placebo	Placebo (single intravenous (IV) bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm B. 1 mg/kg Sugammadex; given 3 minutes after Esmeron®	Sugammadex	Sugammadex (1 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm C. 2 mg/kg Sugammadex; given 3 minutes after Esmeron®	Sugammadex	Sugammadex (2 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm C. 2 mg/kg Sugammadex; given 3 minutes after Esmeron®	Esmeron®	Sugammadex (2 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm E. 6 mg/kg Sugammadex; given 3 minutes after Esmeron®	Sugammadex	Sugammadex (6 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm F. 8 mg/kg Sugammadex; given 3 minutes after Esmeron®	Sugammadex	Sugammadex (8 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm F. 8 mg/kg Sugammadex; given 3 minutes after Esmeron®	Esmeron®	Sugammadex (8 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm J. 4 mg/kg Sugammadex; given 5 minutes after Esmeron®	Esmeron®	Sugammadex (4 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm L. 8 mg/kg Sugammadex; given 5 minutes after Esmeron®	Esmeron®	Sugammadex (8 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm K. 6 mg/kg Sugammadex; given 5 minutes after Esmeron®	Sugammadex	Sugammadex (6 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm K. 6 mg/kg Sugammadex; given 5 minutes after Esmeron®	Esmeron®	Sugammadex (6 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm M. Placebo; given 15 minutes after Esmeron®	Placebo	Placebo (single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm M. Placebo; given 15 minutes after Esmeron®	Esmeron®	Placebo (single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm N. 1 mg/kg Sugammadex; given 15 minutes after Esmeron®	Sugammadex	Sugammadex (1 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm O. 2 mg/kg Sugammadex; given 15 minutes after Esmeron®	Sugammadex	Sugammadex (2 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm O. 2 mg/kg Sugammadex; given 15 minutes after Esmeron®	Esmeron®	Sugammadex (2 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm P. 4 mg/kg Sugammadex; given 15 minutes after Esmeron®	Sugammadex	Sugammadex (4 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm P. 4 mg/kg Sugammadex; given 15 minutes after Esmeron®	Esmeron®	Sugammadex (4 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm Q. 6 mg/kg Sugammadex; given 15 minutes after Esmeron®	Sugammadex	Sugammadex (6 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm Q. 6 mg/kg Sugammadex; given 15 minutes after Esmeron®	Esmeron®	Sugammadex (6 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm R. 8 mg/kg Sugammadex; given 15 minutes after Esmeron®	Esmeron®	Sugammadex (8 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm A. Placebo; given 3 minutes after Esmeron®	Esmeron®	Placebo (single intravenous (IV) bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm B. 1 mg/kg Sugammadex; given 3 minutes after Esmeron®	Esmeron®	Sugammadex (1 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm D. 4 mg/kg Sugammadex; given 3 minutes after Esmeron®	Esmeron®	Sugammadex (4 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm E. 6 mg/kg Sugammadex; given 3 minutes after Esmeron®	Esmeron®	Sugammadex (6 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm I. 2 mg/kg Sugammadex; given 5 minutes after Esmeron®	Esmeron®	Sugammadex (2 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm N. 1 mg/kg Sugammadex; given 15 minutes after Esmeron®	Esmeron®	Sugammadex (1 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm L. 8 mg/kg Sugammadex; given 5 minutes after Esmeron®	Sugammadex	Sugammadex (8 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm D. 4 mg/kg Sugammadex; given 3 minutes after Esmeron®	Sugammadex	Sugammadex (4 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm H. 1 mg/kg Sugammadex; given 5 minutes after Esmeron®	Sugammadex	Sugammadex (1 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm J. 4 mg/kg Sugammadex; given 5 minutes after Esmeron®	Sugammadex	Sugammadex (4 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.
Arm R. 8 mg/kg Sugammadex; given 15 minutes after Esmeron®	Sugammadex	Sugammadex (8 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®.

Primary Outcome Measures

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

Name	Time	Method
Mean Heart Rate at Baseline	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.
Mean Heart Rate at 2 Minutes Following Administration of Study Treatment	2 minutes following administration of study treatment	Mean heart rate at 2 minutes following administration of study treatment was assessed.
Mean Heart Rate at 30 Minutes Following Administration of Study Treatment	30 minutes following administration of study treatment	Mean heart rate at 30 minutes following administration of study treatment was assessed.
Mean Corrected QT Interval (QTc) at Baseline	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.
Mean Corrected QT Interval (QTc) at 2 Minutes Following Administration of Study Treatment	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.
Mean Corrected QT Interval (QTc) at 30 Minutes Following Administration of Study Treatment	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.
Number of Participants Experiencing an Adverse Event	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.