A Bridging Trial Comparing Sugammadex (Org 25969) at 1-2 Post-Tetanic Count (PTC) in Caucasian Participants. Part B (P05974)

Study Overview
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Brief Summary
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The objective of the trial was to establish the dose-response relation of sugammadex given as a reversal agent of rocuronium or vecuronium at 1-2 Post-Tetanic Count (PTC) during sevoflurane anesthesia for Caucasian participants

Official Title
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A Multi -Center, Randomized, Open -Label, Prospective Bridging, Parallel Dose-Finding Trial Comparing Efficacy, Safety and Pharmacokinetics of 5 Doses of Org 25969 Administered at 1-2 PTC After Rocuronium or Vecuronium in Japanese and Caucasian Subjects. Part B: Caucasian Subjects.

Conditions
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Anesthesia, General

Intervention / Treatment
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* Drug: Sugammadex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants of American Society of Anesthesiologists (ASA) class 1 - 3; Participants at least 20 years but under 65 years of age; Caucasian participants ; Participants scheduled for elective surgery requiring muscle relaxation in supine position and under sevoflurane anesthesia, in need of administration of a neuromuscular blocking agent (NMBA), with an anticipated duration of about 1.5- 3 hours; Participants who had given written informed consent. This was obtained before the investigator or the sub-investigator performed any procedures or assessments for the screening, and after the participant was informed about the nature and purpose of the study, the study procedures, and the risks and restrictions of the study. Exclusion criteria: Participants in whom a difficult intubation because of anatomical malformations was expected; Participants known or suspected to have neuromuscular disorders impairing neuromuscular blockade (NMB) and/or significant renal dysfunction (for example a creatinine level > 1.6 mg/dl) and/or severe hepatic 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 expected to interfere with the rocuronium or vecuronium given in this trial, based on the dose and time of administration; Female participants who were pregnant; Female participants of childbearing potential not using birth control or using only oral contraception as birth control; Participants who were breast-feeding; Participants who had already participated in CT 19.4.209B, or in another trial with sugammadex; Participants who had participated in another clinical trial, not preapproved by Organon, within 6 months of entering into CT 19.4.209B.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 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: Sugammadex 0.5 mg/kg (Rocuronium)<br>After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the second twitch (T2) response to Train-of-four (TOF) stimulation, a single dose of 0.5 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 1.0 mg/kg (Rocuronium)<br>After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 1.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 2.0 mg/kg (Rocuronium)<br>After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 2.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 4.0 mg/kg (Rocuronium)<br>After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 4.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 8.0 mg/kg (Rocuronium)<br>After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 8.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 0.5 mg/kg (Vecuronium)<br>After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 0.5 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 1.0 mg/kg (Vecuronium)<br>After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 1.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 2.0 mg/kg (Vecuronium)<br>After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 2.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 4.0 mg/kg (Vecuronium)<br>After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 4.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|
| Experimental: Sugammadex 8.0 mg/kg (Vecuronium)<br>After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 8.0 mg/kg sugammadex was administered IV. | Drug: Sugammadex<br>* After induction of anesthesia an intubation dose of a neuromuscular blocking agent (NMBA) was administered IV: either 0.9 mg/kg rocuronium (arms 1-5) or 0.1 mg/kg vecuronium (arms 6-10). Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary. At reappearance of T2 the randomized single dose of sugammadex (0.5 to 8.0 mg/kg) IV was administered.<br>* Other names: Bridion^TM;|

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 the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation | 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. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached >= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB. | Up to 131:40 (min:sec) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.7 | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB. | Up to 96:24 (min:sec) | 
| Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.8 | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB. | Up to 102:25 (min:sec) | 
| Number of Participants With An Adverse Event (AE) | The number of participants who had at least one AE during treatment and follow-up was assessed. An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | From Screening to 7 post-operative days |