Comparison of 4.0 mg/kg Sugammadex at 1-2 Post Tetanic Counts (PTC) in Renal or Control Patients (19.4.328)(P05769)

Phase 3

Completed

• Conditions: Anesthesia
• Interventions: Drug: sugammadex

• Registration Number: NCT00702715
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The current trial was designed to investigate the effects of 4.0 mg.kg-1 of sugammadex on efficacy, safety and pharmacokinetics in subjects with severe renal impairment in comparison to subjects with normal renal function.

Detailed Description

The results of previous trials showed that the safety profile of sugammadex

observed in subjects with impaired renal function are not appreciably different from subjects with normal renal function. Reoccurrence of neuromuscular blockade was not observed, and sugammadex was safe and generally well tolerated in subjects with severe renal impairment. In a previous trial, subjects (n=15) with severe renal impairment received a dose of 2.0 mg.kg-1 of sugammadex. The effects of the other proposed recommended dose for routine reversal, 4.0 mg.kg-1, on efficacy, safety and pharmacokinetics had not been studied thus far in subjects with severe renal impairment. The objectives of this trial were to assess equivalence with respect to the efficacy of sugammadex in subjects with normal renal function or severe renal impairment, to evaluate the safety of sugammadex in these subject groups and to compare the pharmacokinetic profiles.

Study Timeline

• Study First Submitted: 2008-06-19
• Study First Submitted QC: 2008-06-19
• Study First Posted: 2008-06-20
• Study Start: 2008-09-24
• Primary Completion: 2010-03-15
• Study Completion: 2010-03-15
• Results First Submitted: 2011-03-15
• Results First Submitted QC: 2011-03-15
• Results First Posted: 2011-04-11
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-12
• Last Update Posted: 2017-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

• At least 18 years of age
• ASA class 1-3
• Creatinine clearance (CLcr) < 30 mL/min and no anticipated clinical

indication for high flux hemodialysis during first 24 hours after

sugammadex administration (for renally impaired group) or CLcr >= 80

mL/min (for control group)

-Scheduled for a surgical procedure under general anesthesia with propofol

requiring neuromuscular relaxation with the use of rocuronium

• Scheduled for a surgical procedure in supine position
• Written informed consent

Exclusion Criteria

• Subjects known or suspected to have neuromuscular disorders impairing

neuromuscular blockade and/or significant hepatic dysfunction

• Subjects scheduled for renal transplant surgery
• Subjects known or suspected to have a (family) history of malignant

hyperthermia

-Subjects known or suspected to have an allergy to narcotics, muscle

relaxants or other medication used during general anesthesia

• Subjects receiving fusidic acid, toremifene and/or flucloxacillin
• Subjects who have already participated in a sugammadex trial
• Subjects who have participated in another clinical trial, not pre-approved

by the sponsor, within 30 days of entering into 19.4.328 (P05769)

• Female subjects who are pregnant
• Female subjects who are breast-feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Participants with severe renal impairment	sugammadex	Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.
Participants with normal renal function	sugammadex	Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.

Primary Outcome Measures

Name	Time	Method
Time to Recovery of the T4/T1 Ratio to 0.9.	start of administration of sugammadex to recovery from neuromuscular blockade	Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.

Secondary Outcome Measures

Name	Time	Method
Time to Recovery of the T4/T1 Ratio to 0.8	start of administration of sugammadex to recovery from neuromuscular blockade	Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.
Time to Recovery of T4/T1 Ratio to 0.7	start of administration of sugammadex to recovery from neuromuscular blockade	Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.