Safety and Efficacy of Sugammadex (Org 25969, MK-8616) in Participants With or Having a Past History of Pulmonary Disease (19.4.308) (P05932) (MK-8616-017)

Study Overview
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Brief Summary
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The purpose of the trial is to research the safety and to show faster recovery after administration of 2.0 mg/kg or 4.0 mg/kg sugammadex (Org 25969, MK-8616) given as a reversal agent for 0.6 mg/kg (0.15 mg/kg maintenance dose) rocuronium (Zemuron®) in participants diagnosed with or having a history of pulmonary disease. All drug administration will be via the intravenous (IV) route.

Official Title
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A Multicenter, Randomized, Parallel Group, Comparative, Safety-Assessor Blinded, Phase IIIa Trial in Adult Surgical Subjects Under General Anesthesia at Increased Risk for Pulmonary Complications

Conditions
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Anesthesia, General

Intervention / Treatment
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* Drug: Sugammadex
* Drug: Rocuronium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) Class 1 to 3; Has been diagnosed with or having a past history of pulmonary disease; Is scheduled for elective surgical procedure under general anesthesia requiring neuromuscular block with the use of rocuronium; Is scheduled for surgery in supine position; Has given written informed consent; Exclusion Criteria: Is expected to have a difficult intubation due to anatomical malformations; Has known or suspected of having neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction; Has known or suspected of having a (family) history of malignant hyperthermia; Has known or suspected of having an allergy to narcotics, muscle relaxants or other medications used during surgery; Is receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics and Mg2+; Is a female who is pregnant or breast-feeding; Is a female of childbearing potential not using an acceptable method of birth control [condom or diaphragm with spermicide, vasectomized partner (> 6 months), IUD, abstinence] or using only hormonal contraception as birth control; Has already participated in a sugammadex trial including Protocol 19.4.308; Has participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into Protocol 19.4.308.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rocuronium + Sugammadex 2.0 mg/kg<br>After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 2.0 mg/kg. | Drug: Sugammadex<br>* Sugammadex solution for injection.<br>* Other names: Org 25969, MK-8616, Bridion®;Drug: Rocuronium<br>* Rocuronium bromide solution for injection.<br>* Other names: Zemuron®;|
| Experimental: Rocuronium + Sugammadex 4.0 mg/kg<br>After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 4.0 mg/kg. | Drug: Sugammadex<br>* Sugammadex solution for injection.<br>* Other names: Org 25969, MK-8616, Bridion®;Drug: Rocuronium<br>* Rocuronium bromide solution for injection.<br>* Other names: Zemuron®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.9 in Participants With or Having a Past History of Pulmonary Disease | The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.9 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX. | Up to 90 minutes | 
| Percentage of Participants Experiencing ≥1 Adverse Event(s) (AE) | The percentage of participants experiencing ≥1 AE(s) was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | Up to 7 days | 
| Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event (AE) | The percentage of participants discontinuing from study treatment due to an AE was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | Up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.7 in Participants With or Having a Past History of Pulmonary Disease | The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.7 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX. | Up to 90 minutes | 
| Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.8 in Participants With or Having a Past History of Pulmonary Disease | The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.8 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX. | Up to 90 minutes | 
| Level of Consciousness Assessment 1: Prior to Transfer to the Recovery Room Following Extubation | The level of consciousness prior to transfer to the recovery room was determined by the clinician for each participant. Each participants was assigned 1 of 3 potential levels of consciousness: 1) awake and oriented; 2) arousable with minimal stimulation; or 3) responsive only to tactile stimulation. | Up to 6 hours (prior to transfer to the recovery room after extubation) | 
| Level of Consciousness Assessment 2: Prior to Discharge From the Recovery Room | The level of consciousness prior to discharge from the recovery room was determined by the clinician for each participant. Each participants was assigned 1 of 3 potential levels of consciousness: 1) awake and oriented; 2) arousable with minimal stimulation; or 3) responsive only to tactile stimulation. | Up to 6 hours (prior to discharge from the recovery room) | 
| Five-Second Head Lift Assessment 1: Prior to Transfer to the Recovery Room Following Extubation | The ability of each cooperative (based on clinician determination) participant to perform a 5-second head lift was determined by the clinician. Participants were rated as either able or not able to complete the head lift task. | Up to 6 hours (prior to transfer to the recovery room after extubation) | 
| Five-Second Head Lift Assessment 2: Prior to Discharge From the Recovery Room | The ability of each cooperative (based on clinician determination) participant to perform a 5-second head lift was determined by the clinician. Participants were rated as either able or not able to complete the head lift task. | Up to 6 hours (prior to discharge from the recovery room) | 
| General Muscle Weakness Assessment 1: Prior to Transfer to the Recovery Room Following Extubation | Each cooperative (based on clinician determination) participant was assessed by a clinician to determine if there was muscle weakness. Participants were rated as having or not having muscle weakness by the clinician. | Up to 6 hours (prior to transfer to the recovery room after extubation) | 
| General Muscle Weakness Assessment 2: Prior to Discharge From the Recovery Room | Each cooperative (based on clinician determination) participant was assessed by a clinician to determine if there was muscle weakness. Participants were rated as having or not having muscle weakness by the clinician. | Up to 6 hours (prior to discharge from the recovery room) |