Comparison of Sugammadex With Neostigmine During Laparoscopic Cholecystectomy or Appendectomy (P05699)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00724932
• Collaborator: (none)
• Enrollment: 140
• Arms: 2
• Actual Duration (Months): 9.6

Study Details

Study Description

Brief Summary

The current trial was designed to demonstrate faster recovery from a neuromuscular blockade (NMB) induced by rocuronium after reversal at 1-2 Post Tetanic Count (PTC) by 4.0 mg.kg-1 sugammadex compared to 50 µg.kg-1 neostigmine at reappearance of second twitch (T2) in participants undergoing laparoscopic cholecystectomy or appendectomy under propofol anesthesia, to compare safety and to evaluate operating room and Post Anesthetic Care Unit (PACU) length of stay.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia, General	Drug: Rocuronium; Drug: Sugammadex; Drug: Neostigmine; Drug: Atropine	Phase 3

Detailed Description

In those surgical procedures where a neuromuscular block is desired for intubation and/or avoid unwanted muscular activity, anesthesiologists may use a more profound NMB until the end of surgery, e.g. in open abdominal procedures or during laparoscopic procedures in order to improve surgical conditions. Reversal with sugammadex at a dose of 4.0 mg.kg-1 at 1-2 PTC after an intubation dose of 0.6 mg.kg-1 or maintenance dosing rocuronium has been found to be both safe and efficacious in previous clinical trials but has never been investigated exclusively in participants undergoing laparoscopic cholecystectomy or appendectomy.

With sugammadex profound muscle relaxation may now be provided right up to the end of the surgical procedure. This may lead to improved Patient Outcomes, such as improvement in the time from end of surgery to the discharge to the PACU. In this multi-center, randomized, parallel-group, active-controlled, safety-assessor blinded trial such benefits will be further investigated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Parallel-group, Comparative, Active-controlled, Safety-assessor Blinded Trial in Adult Subjects Comparing the Efficacy and Safety of Sugammadex (SCH 900616, ORG 25969) Administered at 1-2 PTC With Neostigmine Administered at Reappearance of T2 in Subjects Undergoing Laparoscopic Cholecystectomy or Appendectomy Under Propofol Anesthesia
• Actual Study Start Date: Jul 16, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: May 3, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sugammadex 4.0 mg.kg-1 sugammadex at 1-2 PTC	Drug: Rocuronium; Participants will receive an intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After this dose, maintenance doses of 0.1-0.2 mg.kg-1 rocuronium may be given.; Other Names: rocuronium bromide Esmeron® ; Drug: Sugammadex; After the last dose of rocuronium has been administered, participants will receive, according to the randomization, a single bolus dose of 4.0 mg.kg-1 sugammadex at 1-2 PTC.; Other Names: Org 25969 SCH 900616 MK-8616 Bridion®
Experimental: Neostigmine 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2	Drug: Rocuronium; Participants will receive an intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After this dose, maintenance doses of 0.1-0.2 mg.kg-1 rocuronium may be given.; Other Names: rocuronium bromide Esmeron® ; Drug: Neostigmine; After the last dose of rocuronium has been administered, participants will receive, according to the randomization, 50 μg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2.; Other Names: Prostigmin® ; Drug: Atropine; After the last dose of rocuronium has been administered, participants will receive, according to randomization, 10 μg.kg-1 atropine (with neostigmine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2.; Other Names: atropine sulfate

Outcome Measures

Primary Outcome Measures

1. Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 [From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes)]

   Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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.

Secondary Outcome Measures

1. Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 [From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes)]

   Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB.

2. Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 [From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes)]

   Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB.

3. Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs [From signing of informed consent to end of trial (7 days after surgery)]

   An SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect. Participants were monitored for occurrence SAEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.

4. Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs [From signing of informed consent to end of trial (7 days after surgery)]

   An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.

Other Outcome Measures

1. Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 [From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes)]

   Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). Faster times to recovery of the T4/T1 Ratios to 0.5 and 0.6 indicate faster recoveries from NMB.

2. Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 [From start of last dose of rocuronium to recovery of T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 (ranging from ~12 minutes to ~36 minutes)]

   Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). A faster time to recovery of the T4/T1 Ratio indicates a faster recovery from NMB.

3. Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group [From last dose of rocuronium to 1-2 PTC (up to ~9 minutes)]

   The time of 1-2 PTC refers to when 1-2 twitches are generated after tetanic stimulation. Time to 1-2 PTC is the time point of the last single twitch >0 or baseline (in case of noise or direct stimulation) within the sequence of a PTC measurement. 1-2 PTC was the target depth of NMB at which sugammadex was to be administered.

4. Time From Start of Administration of the Last Dose of Rocuronium to the Time of Reappearance of T2 in the 50 μg.Kg-1 Neostigmine Group [From last dose of rocuronium to reappearance of T2 (up to ~26 minutes)]

   The time of reappearance of T2 refers to when the second twitch reappears after TOF stimulation. Reappearance of T2 was the target depth of NMB at which neostigmine was to be administered.

5. Mean Systolic Blood Pressure [At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)]

   Systolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).

6. Mean Diastolic Blood Pressure [At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)]

   Diastolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).

7. Mean Heart Rate [At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)]

   Heart Rate was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).

8. Number of Participants Who Had Physical Examinations [At screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery)]

   Physical examinations were to be conducted at screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery).

9. Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events [From induction of anesthesia to recovery from NMB (up to ~3 hours)]

   Events were to be collected for the entire period of neuromuscular transmission monitoring and were defined as an occurrence that resulted or could have resulted in: death; a serious deterioration in the state of health of a user; an occurrence which might, if it recurred, lead to death or serious deterioration in health; inaccuracy as well as any inadequacy in the labeling or instructions which could cause misuse or incorrect maintenance or adjustment which might lead to a death or serious deterioration in health; an examination of the medical device or the information supplied with the medical device indicated some factor with the potential for an incident involving death or serious deterioration in health; malfunction or deterioration in characteristics and/or performance of a medical device, which might lead to death, or serious deterioration in health; technical/medical recalls involving risk of death or serious deterioration in the state of health of the user.

10. Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values) [Up to 30 minutes after IMP administration]

    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 magnitudes (heights) of the 1st and 4th twitches, respectively, after TOF stimulation. The T4/T1 Ratio is expressed as a decimal of up to 1.0. A higher ratio indicates greater recovery from NMB. A decline in the T4/T1 ratio from >=0.9 (indicating a recovery from NMB) to <0.8 for at least three consecutive TOF values was considered to be a reoccurrence of NMB.

11. Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement) [Up to 24 hours after IMP administration]

    Clinical evidence of reoccurrence of NMB or residual NMB was assessed by oxygen saturation (by pulse oximetry) and breath frequency measurements as per routine practice after anesthesia and neuromuscular monitoring.

12. Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium [Up to 7 days after IMP administration]

    Any evidence of events due to a possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium, was to be recorded.

13. Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites [Up to PACU discharge (up to ~4.5 hours)]

    The monitoring of clinical signs of recovery was to be conducted based on the routine anesthetic procedures at each site.

14. Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study [Up to 30 days after IMP administration]

    Thirty days after administration of IMP, female participants of childbearing potential were asked whether they became pregnant during the trial and male participants were asked whether their partner (if of childbearing potential) became pregnant during the trial.

15. Time From Operating Room Admission to Operating Room Discharge Ready [From Operating Room admission to Operating Room discharge ready (up to ~3 hours)]

    The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of ≥0.9 and the participant's wound dressing was in place.

16. Time From Operating Room Admission to Actual Operating Room Discharge [From Operating Room admission to actual Operating Room discharge (up to ~3 hours)]

    The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.

17. Time From Operating Room Discharge Ready to Actual Operating Room Discharge [From Operating Room discharge ready to actual Operating Room discharge (up to ~5 minutes)]

    The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.

18. Time From Start of IMP Administration to T4/T1 Ratio of <=0.60, >0.60 - <=0.70, >0.70 - <=0.80, >0.80 - <0.90 and >=0.90 [From start of IMP administration to recovery of the T4/T1 ratio to the designated value (ranging from ~1 minute to ~10 minutes)]

    The time of IMP administration was defined as the actual time at which IMP administration was started.

19. Time From Start of IMP Administration to Tracheal Extubation [From start of IMP administration to tracheal extubation (up to ~21 minutes)]

    The time of IMP administration was defined as the actual time at which IMP administration was started. The time of tracheal extubation was defined as the actual time at which the participant was extubated.

20. Time From Start of IMP Administration to Operating Room Discharge Ready [From start of IMP administration to Operating Room discharge ready (up to ~21 minutes)]

    The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place.

21. Time From Start of IMP Administration to Actual Operating Room Discharge [From start of IMP administration to actual Operating Room discharge (up to ~26 minutes)]

    The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.

22. Time From Tracheal Extubation to Operating Room Discharge Ready [From tracheal extubation to Operating Room discharge ready (up to ~1 minute)]

    The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place.

23. Time From Tracheal Extubation to Actual Operating Room Discharge [From tracheal extubation to actual OR discharge (up to ~5 minutes)]

    The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.

24. Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready [From Operating Room discharge ready to PACU discharge ready (up to ~33 minutes)]

    The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.

25. Time From Operating Room Discharge Ready to Actual PACU Discharge [From Operating Room discharge ready to actual PACU discharge (up to ~4.5 hours)]

    The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.

26. Time From Actual Operating Room Discharge to PACU Discharge Ready [From actual Operating Room discharge to PACU discharge ready (up to ~30 minutes)]

    The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.

27. Time From Actual Operating Room Discharge to Actual PACU Discharge [From actual Operating Room discharge to actual PACU discharge (up to ~4.4 hours)]

    The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.

28. Time From PACU Admit to PACU Discharge Ready [From PACU admit to PACU discharge ready (up to ~25 minutes)]

    The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.

29. Time From PACU Admit to Actual PACU Discharge [From PACU admit to actual PACU discharge (up to ~4.3 hours)]

    The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants of American Society of Anesthesiologists class 1-3

• Participants of age above or equal to the age of 18 years

• Participants who are scheduled to undergo a laparoscopic cholecystectomy or appendectomy under general anesthesia requiring neuromuscular relaxation with rocuronium, and if applicable, maintenance of neuromuscular blockade

• Participants who have given written informed consent

Exclusion Criteria:

• Participants in whom a difficult intubation because of anatomical malformations is expected

• Participants known or suspected to have neuromuscular disorders affecting NMB

• Participants known or suspected to have a significant renal dysfunction

• Participants known or suspected to have a severe hepatic dysfunction

• Participants known or suspected to have (family) history of malignant hyperthermia

• Participants known or suspected to have an allergy to opioids, muscle relaxants or other medication used during general anesthesia

• Participants in whom the use of neostigmine and/or atropine is contraindicated

• Female participants who are pregnant (pregnancy will be excluded for women both from medical history and by a human chorionic gonadotropin (hCG) test within 24h before surgery, except for women who are not of childbearing potential, i.e. at least 2 years menopausal or have undergone tubal ligation or a hysterectomy)

• Female participants who are breast-feeding

• Participants who participated in another clinical trial not pre-approved by the sponsor, within 30 days of entering into trial 19.4.318 (P05699)

• Participants who have already participated in a sugammadex trial

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg. 1970 Nov-Dec;49(6):924-34.
• Apfel CC, Kranke P, Eberhart LH, Roos A, Roewer N. Comparison of predictive models for postoperative nausea and vomiting. Br J Anaesth. 2002 Feb;88(2):234-40. Review.
• Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700.
• Caldwell JE. Reversal of residual neuromuscular block with neostigmine at one to four hours after a single intubating dose of vecuronium. Anesth Analg. 1995 Jun;80(6):1168-74.
• Irie T, Uekama K. Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J Pharm Sci. 1997 Feb;86(2):147-62. Review.
• Suresh D, Carter JA, Whitehead JP, Goldhill DR, Flynn PJ. Cardiovascular changes at antagonism of atracurium. Effects of different doses of premixed neostigmine and glycopyrronium in a ratio of 5:1. Anaesthesia. 1991 Oct;46(10):877-80.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00724932
• Other Study ID Numbers: P05699; 19.4.318; MK-8616-002; 2007-007951-14
• First Posted: Jul 30, 2008
• Last Update Posted: May 16, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Atropine; Bromides; Rocuronium; Neostigmine

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 10 sites in Germany, Russia, Finland and the United Kingdom between July 2008 and March 2009.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 Post Tetanic Count (PTC)	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine: atropine) at reappearance of the second twitch (T2)
Period Title: Overall Study
STARTED	70	70
COMPLETED	65	67
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Sugammadex	Neostigmine	Total
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2	Total of all reporting groups
Overall Participants	66	67	133
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (16)	51 (14)	51 (15)
Sex: Female, Male (Count of Participants)
Female	49 74.2%	43 64.2%	92 69.2%
Male	17 25.8%	24 35.8%	41 30.8%

Outcome Measures

1. Primary Outcome

Title	Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9
Description	Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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.
Time Frame	From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes)

Outcome Measure Data

Analysis Population Description

The Intent-To-Treat (ITT) Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Geometric Mean (95% Confidence Interval) [minutes]	2.4	8.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sugammadex, Neostigmine
	Comments	To evaluate the efficacy of sugammadex compared to neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.9 was calculated using a two-way analysis of variance (ANOVA) model adjusted for treatment group and trial site.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Testing was performed using a two-sided test at the 0.05 significance level. There was only one primary comparison, therefore no adjustment for multiplicity was required.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Final Values)
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; 2.8 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sugammadex is the numerator and neostigmine the denominator. The estimated value for the geometric mean ratio presents how many times the geometric mean time to recovery of the T4/T1 ratio to 0.9 was faster with sugammadex compared to neostigmine.

2. Secondary Outcome

Title	Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7
Description	Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB.
Time Frame	From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Imputed recovery times were used in cases of missing recovery times.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Geometric Mean (95% Confidence Interval) [minutes]	1.6	4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sugammadex, Neostigmine
	Comments	To evaluate the efficacy of sugammadex compared to neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.7 was calculated using a two-way ANOVA model adjusted for treatment group and trial site.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value is not adjusted for multiplicity.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Final Values)
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; 2.1 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sugammadex is the numerator and neostigmine the denominator. The estimated value for the geometric mean ratio presents how many times the geometric mean time to recovery of the T4/T1 ratio to 0.7 was faster with sugammadex compared to neostigmine.

3. Other Pre-specified Outcome

Title	Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6
Description	Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). Faster times to recovery of the T4/T1 Ratios to 0.5 and 0.6 indicate faster recoveries from NMB.
Time Frame	From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. No imputation was done for missing times to recovery of the T4/T1 ratio to 0.5 and 0.6.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Recovery of T4/T1 Ratio to 0.5	1.3	2.8
Recovery of T4/T1 Ratio to 0.6	1.5	3.4

4. Other Pre-specified Outcome

Title	Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9
Description	Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). A faster time to recovery of the T4/T1 Ratio indicates a faster recovery from NMB.
Time Frame	From start of last dose of rocuronium to recovery of T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 (ranging from ~12 minutes to ~36 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. No imputation was done for missing times from administration of last dose of rocuronium to recovery of the T4/T1 ratio to 0.5, 0.6, 0.7, 0.8 and 0.9.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Recovery of T4/T1 ratio to 0.5	11.7	30.0
Recovery of T4/T1 ratio to 0.6	11.9	30.7
Recovery of T4/T1 ratio to 0.7	12.1	31.6
Recovery of T4/T1 ratio to 0.8	12.5	33.2
Recovery of T4/T1 ratio to 0.9 (N=65, N=61)	13.3	35.2

5. Other Pre-specified Outcome

Title	Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group
Description	The time of 1-2 PTC refers to when 1-2 twitches are generated after tetanic stimulation. Time to 1-2 PTC is the time point of the last single twitch >0 or baseline (in case of noise or direct stimulation) within the sequence of a PTC measurement. 1-2 PTC was the target depth of NMB at which sugammadex was to be administered.
Time Frame	From last dose of rocuronium to 1-2 PTC (up to ~9 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received sugammadex and had at least one efficacy measurement. The participants who received neostigmine were not included in this analysis.

Arm/Group Title	Sugammadex Only
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC
Measure Participants	66
Geometric Mean (95% Confidence Interval) [minutes]	8.9

6. Other Pre-specified Outcome

Title	Time From Start of Administration of the Last Dose of Rocuronium to the Time of Reappearance of T2 in the 50 μg.Kg-1 Neostigmine Group
Description	The time of reappearance of T2 refers to when the second twitch reappears after TOF stimulation. Reappearance of T2 was the target depth of NMB at which neostigmine was to be administered.
Time Frame	From last dose of rocuronium to reappearance of T2 (up to ~26 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received neostigmine and had at least one efficacy measurement. The participants who received sugammadex were not included in this analysis.

Arm/Group Title	Neostigmine Only
Arm/Group Description	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	65
Geometric Mean (95% Confidence Interval) [minutes]	25.6

7. Other Pre-specified Outcome

Title	Mean Systolic Blood Pressure
Description	Systolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
Time Frame	At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Screening	132.7 (17.7)	133.9 (19.1)
Pre-rocuronium	98.2 (13.9)	101.6 (18.2)
Pre-IMP	122.1 (16.5)	121.3 (18.8)
2 minutes post-IMP (N=65, N=65)	122.5 (18.8)	122.5 (20.4)
5 minutes post-IMP	122.6 (17.7)	118.0 (22.3)
10 minutes post-IMP (N=66, N=66)	124.0 (17.8)	119.3 (23.7)
30 minutes post-IMP (N=65, N=66)	132.9 (17.4)	131.7 (23.0)
Post-anesthetic visit (N=66, N=66)	127.3 (16.6)	125.4 (17.1)

8. Other Pre-specified Outcome

Title	Mean Diastolic Blood Pressure
Description	Diastolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
Time Frame	At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Screening	80.9 (9.9)	82.8 (9.4)
Pre-rocuronium	58.2 (11.6)	58.3 (10.1)
Pre-IMP	72.8 (12.1)	72.5 (12.8)
2 minutes post-IMP (N=65, N=65)	73.4 (11.8)	72.6 (11.8)
5 minutes post-IMP	72.4 (11.4)	69.2 (13.5)
10 minutes post-IMP (N=66, N=66)	71.8 (12.8)	68.7 (14.9)
30 minutes post-IMP (N=65, N=66)	74.3 (10.9)	73.1 (13.5)
Post-anesthetic visit (N=66, N=66)	76.7 (9.4)	75.2 (10.8)

9. Other Pre-specified Outcome

Title	Mean Heart Rate
Description	Heart Rate was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
Time Frame	At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Screening	72.9 (11.0)	74.6 (11.4)
Pre-rocuronium	63.4 (13.4)	63.6 (12.4)
Pre-IMP	68.3 (11.0)	68.0 (12.3)
2 minutes post-IMP (N=65, N=65)	66.0 (12.4)	65.3 (12.4)
5 minutes post-IMP	64.9 (12.3)	57.1 (10.8)
10 minutes post-IMP (N=66, N=66)	67.3 (12.4)	56.3 (11.4)
30 minutes post-IMP (N=65, N=66)	73.1 (12.2)	65.1 (11.2)
Post-anesthetic visit (N=66, N=66)	72.7 (11.7)	71.9 (71.9)

10. Secondary Outcome

Title	Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8
Description	Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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). A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB.
Time Frame	From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Imputed recovery times were used in cases of missing recovery times.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Geometric Mean (95% Confidence Interval) [minutes]	1.9	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sugammadex, Neostigmine
	Comments	To evaluate the efficacy of sugammadex compared to neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.8 was calculated using a two-way ANOVA model adjusted for treatment group and trial site.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p-value is not adjusted for multiplicity.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Final Values)
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; 2.5 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sugammadex is the numerator and neostigmine the denominator. The estimated value for the geometric mean ratio presents how many times the geometric mean time to recovery of the T4/T1 ratio to 0.8 was faster with sugammadex compared to neostigmine.

11. Other Pre-specified Outcome

Title	Number of Participants Who Had Physical Examinations
Description	Physical examinations were to be conducted at screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery).
Time Frame	At screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP. As there was no specific physical examination case report form used in this study, data on whether or not a physical examination was conducted were not recorded.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	0	0

12. Other Pre-specified Outcome

Title	Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events
Description	Events were to be collected for the entire period of neuromuscular transmission monitoring and were defined as an occurrence that resulted or could have resulted in: death; a serious deterioration in the state of health of a user; an occurrence which might, if it recurred, lead to death or serious deterioration in health; inaccuracy as well as any inadequacy in the labeling or instructions which could cause misuse or incorrect maintenance or adjustment which might lead to a death or serious deterioration in health; an examination of the medical device or the information supplied with the medical device indicated some factor with the potential for an incident involving death or serious deterioration in health; malfunction or deterioration in characteristics and/or performance of a medical device, which might lead to death, or serious deterioration in health; technical/medical recalls involving risk of death or serious deterioration in the state of health of the user.
Time Frame	From induction of anesthesia to recovery from NMB (up to ~3 hours)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Number [participants]	0 0%	0 0%

13. Other Pre-specified Outcome

Title	Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values)
Description	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 magnitudes (heights) of the 1st and 4th twitches, respectively, after TOF stimulation. The T4/T1 Ratio is expressed as a decimal of up to 1.0. A higher ratio indicates greater recovery from NMB. A decline in the T4/T1 ratio from >=0.9 (indicating a recovery from NMB) to <0.8 for at least three consecutive TOF values was considered to be a reoccurrence of NMB.
Time Frame	Up to 30 minutes after IMP administration

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Number [participants]	0 0%	0 0%

14. Other Pre-specified Outcome

Title	Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement)
Description	Clinical evidence of reoccurrence of NMB or residual NMB was assessed by oxygen saturation (by pulse oximetry) and breath frequency measurements as per routine practice after anesthesia and neuromuscular monitoring.
Time Frame	Up to 24 hours after IMP administration

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Number [participants]	1 1.5%	0 0%

15. Other Pre-specified Outcome

Title	Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium
Description	Any evidence of events due to a possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium, was to be recorded.
Time Frame	Up to 7 days after IMP administration

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received sugammadex. Participants who received neostigmine were excluded from this analysis.

Arm/Group Title	Sugammadex Only
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC
Measure Participants	66
Number [participants]	0 0%

16. Other Pre-specified Outcome

Title	Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites
Description	The monitoring of clinical signs of recovery was to be conducted based on the routine anesthetic procedures at each site.
Time Frame	Up to PACU discharge (up to ~4.5 hours)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Number [participants]	NA NaN	NA NaN

17. Other Pre-specified Outcome

Title	Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study
Description	Thirty days after administration of IMP, female participants of childbearing potential were asked whether they became pregnant during the trial and male participants were asked whether their partner (if of childbearing potential) became pregnant during the trial.
Time Frame	Up to 30 days after IMP administration

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Number [participants]	0 0%	0 0%

18. Other Pre-specified Outcome

Title	Time From Operating Room Admission to Operating Room Discharge Ready
Description	The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of ≥0.9 and the participant's wound dressing was in place.
Time Frame	From Operating Room admission to Operating Room discharge ready (up to ~3 hours)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Mean (Standard Deviation) [minutes]	154 (46)	165 (55)

19. Other Pre-specified Outcome

Title	Time From Operating Room Admission to Actual Operating Room Discharge
Description	The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.
Time Frame	From Operating Room admission to actual Operating Room discharge (up to ~3 hours)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	158 (47)	169 (58)

20. Other Pre-specified Outcome

Title	Time From Operating Room Discharge Ready to Actual Operating Room Discharge
Description	The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.
Time Frame	From Operating Room discharge ready to actual Operating Room discharge (up to ~5 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	4 (5)	5 (6)

21. Other Pre-specified Outcome

Title	Time From Start of IMP Administration to T4/T1 Ratio of <=0.60, >0.60 - <=0.70, >0.70 - <=0.80, >0.80 - <0.90 and >=0.90
Description	The time of IMP administration was defined as the actual time at which IMP administration was started.
Time Frame	From start of IMP administration to recovery of the T4/T1 ratio to the designated value (ranging from ~1 minute to ~10 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Data not collected. In Protocol Amendment 2, this outcome measure was removed.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	0	0

22. Other Pre-specified Outcome

Title	Time From Start of IMP Administration to Tracheal Extubation
Description	The time of IMP administration was defined as the actual time at which IMP administration was started. The time of tracheal extubation was defined as the actual time at which the participant was extubated.
Time Frame	From start of IMP administration to tracheal extubation (up to ~21 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Mean (Standard Deviation) [minutes]	14 (8)	21 (11)

23. Other Pre-specified Outcome

Title	Time From Start of IMP Administration to Operating Room Discharge Ready
Description	The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place.
Time Frame	From start of IMP administration to Operating Room discharge ready (up to ~21 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Mean (Standard Deviation) [minutes]	15 (8)	21 (11)

24. Other Pre-specified Outcome

Title	Time From Start of IMP Administration to Actual Operating Room Discharge
Description	The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.
Time Frame	From start of IMP administration to actual Operating Room discharge (up to ~26 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	19 (9)	26 (13)

25. Other Pre-specified Outcome

Title	Time From Tracheal Extubation to Operating Room Discharge Ready
Description	The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place.
Time Frame	From tracheal extubation to Operating Room discharge ready (up to ~1 minute)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Mean (Standard Deviation) [minutes]	1 (6)	0 (6)

26. Other Pre-specified Outcome

Title	Time From Tracheal Extubation to Actual Operating Room Discharge
Description	The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.
Time Frame	From tracheal extubation to actual OR discharge (up to ~5 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	5 (7)	5 (6)

27. Other Pre-specified Outcome

Title	Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready
Description	The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
Time Frame	From Operating Room discharge ready to PACU discharge ready (up to ~33 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Mean (Standard Deviation) [minutes]	28 (27)	33 (40)

28. Other Pre-specified Outcome

Title	Time From Operating Room Discharge Ready to Actual PACU Discharge
Description	The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of >=0.9 and the participant's wound dressing was in place. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
Time Frame	From Operating Room discharge ready to actual PACU discharge (up to ~4.5 hours)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	65
Mean (Standard Deviation) [minutes]	268 (348)	210 (283)

29. Other Pre-specified Outcome

Title	Time From Actual Operating Room Discharge to PACU Discharge Ready
Description	The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
Time Frame	From actual Operating Room discharge to PACU discharge ready (up to ~30 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	24 (28)	29 (40)

30. Other Pre-specified Outcome

Title	Time From Actual Operating Room Discharge to Actual PACU Discharge
Description	The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
Time Frame	From actual Operating Room discharge to actual PACU discharge (up to ~4.4 hours)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	264 (347)	207 (284)

31. Other Pre-specified Outcome

Title	Time From PACU Admit to PACU Discharge Ready
Description	The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score >=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
Time Frame	From PACU admit to PACU discharge ready (up to ~25 minutes)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	20 (28)	25 (40)

32. Other Pre-specified Outcome

Title	Time From PACU Admit to Actual PACU Discharge
Description	The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
Time Frame	From PACU admit to actual PACU discharge (up to ~4.3 hours)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	64
Mean (Standard Deviation) [minutes]	260 (347)	203 (284)

33. Secondary Outcome

Title	Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs
Description	An SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect. Participants were monitored for occurrence SAEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.
Time Frame	From signing of informed consent to end of trial (7 days after surgery)

Outcome Measure Data

Analysis Population Description

The All-Subjects-Treated (AST) Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Pre-treatment SAE	1 1.5%	0 0%
Post-treatment SAE	4 6.1%	6 9%

34. Secondary Outcome

Title	Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs
Description	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.
Time Frame	From signing of informed consent to end of trial (7 days after surgery)

Outcome Measure Data

Analysis Population Description

The AST Population consisted of all randomized participants who received IMP.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC	Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Measure Participants	66	67
Pre-treatment non-serious AE	38 57.6%	34 50.7%
Post-treatment non-serious AE	65 98.5%	65 97%

Adverse Events

Time Frame	Up to 7 days after IMP administration
Adverse Event Reporting Description	The AST Population consisted of all randomized participants who received IMP. Serious Adverse Events (SAEs) include both pre-treatment (from signing of informed consent to start of IMP administration) and post-treatment (from start of IMP administration to 7 days after IMP administration) SAEs.
Arm/Group Title	Sugammadex		Neostigmine
Arm/Group Description	Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC		Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine: atropine) at reappearance of T2
All Cause Mortality
	Sugammadex		Neostigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sugammadex		Neostigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/66 (7.6%)		6/67 (9%)
Gastrointestinal disorders
Colitis	1/66 (1.5%)	1	0/67 (0%)	0
Pancreatitis acute	0/66 (0%)	0	1/67 (1.5%)	1
Injury, poisoning and procedural complications
Operative haemorrhage	0/66 (0%)	0	1/67 (1.5%)	1
Post procedural complication	1/66 (1.5%)	1	1/67 (1.5%)	1
Procedural nausea	1/66 (1.5%)	1	0/67 (0%)	0
Procedural pain	0/66 (0%)	0	1/67 (1.5%)	1
Procedural vomiting	1/66 (1.5%)	1	0/67 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle rigidity	1/66 (1.5%)	1	0/67 (0%)	0
Nervous system disorders
Sedation	0/66 (0%)	0	1/67 (1.5%)	1
Vascular disorders
Vascular calcification	1/66 (1.5%)	1	0/67 (0%)	0
Vascular thrombosis limb	0/66 (0%)	0	1/67 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Sugammadex		Neostigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/66 (97%)		63/67 (94%)
Gastrointestinal disorders
Abdominal Pain	5/66 (7.6%)	5	4/67 (6%)	4
Constipation	6/66 (9.1%)	6	3/67 (4.5%)	3
Dry mouth	0/66 (0%)	0	4/67 (6%)	4
Flatulence	2/66 (3%)	2	4/67 (6%)	4
Nausea	16/66 (24.2%)	17	12/67 (17.9%)	13
Vomiting	8/66 (12.1%)	8	7/67 (10.4%)	7
Injury, poisoning and procedural complications
Anaesthetic complication cardiac	1/66 (1.5%)	1	9/67 (13.4%)	9
Procedural nausea	3/66 (4.5%)	3	5/67 (7.5%)	5
Procedural pain	60/66 (90.9%)	70	60/67 (89.6%)	72
Procedural vomiting	3/66 (4.5%)	3	5/67 (7.5%)	5
Investigations
C-reactive protein increased	8/66 (12.1%)	8	6/67 (9%)	6
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	5/66 (7.6%)	5	3/67 (4.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.