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 2CompletedNCT03519854

Merck Sharp & Dohme LLC99 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Neuromuscular Blockade

Interventions

Placebo

Eligibility

Sex: MALEMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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).

Time frame: Up to 70 minutes following administration of study treatment

Secondary Outcomes

Mean Heart Rate at Baseline

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.

Time frame: Up to 45 minutes prior to study treatment administration

Mean Heart Rate at 2 Minutes Following Administration of Study Treatment

Mean heart rate at 2 minutes following administration of study treatment was assessed.

Time frame: 2 minutes following administration of study treatment

Mean Heart Rate at 30 Minutes Following Administration of Study Treatment

Mean heart rate at 30 minutes following administration of study treatment was assessed.

Time frame: 30 minutes following administration of study treatment

Mean Corrected QT Interval (QTc) at Baseline

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.

Time frame: Up to 45 minutes prior to study treatment administration

Mean Corrected QT Interval (QTc) at 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.

Time frame: 2 minutes following administration of study treatment

Mean Corrected QT Interval (QTc) at 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.

Time frame: 30 minutes following administration of study treatment

Number of Participants Experiencing an Adverse Event

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.

Time frame: Up to 7 days following administration of study treatment