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

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.

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00552929
Enrollment
102
Registered
2007-11-02
Start date
2005-10-04
Completion date
2006-09-15
Last updated
2019-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anesthesia, General

Brief summary

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

Interventions

DRUGSugammadex

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.

Sponsors

Merck Sharp & Dohme LLC
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) StimulationUp to 131:40 (min:sec)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.

Secondary

MeasureTime frameDescription
Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.7Up to 96:24 (min:sec)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.
Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.8Up to 102:25 (min:sec)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.
Number of Participants With An Adverse Event (AE)From Screening to 7 post-operative daysThe 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.

Participant flow

Recruitment details

The trial was conducted in seven centers in Europe: one center in Belgium, one center in Denmark, three centers in France, and two centers in The Netherlands.

Participants by arm

ArmCount
Sugammadex 0.5 mg/kg (Rocuronium)
Sugammadex 0.5 mg/kg administered as a single-bolus intravenous (IV) dose at 1-2 posttetanic count (PTC) after 0.9 mg/kg rocuronium (single-bolus IV dose) for intubation, followed by maintenance doses of rocuronium 0.1-0.2 mg/kg if necessary
9
Sugammadex 1.0 mg/kg (Rocuronium)
Sugammadex 1.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.9 mg/kg rocuronium (single-bolus IV dose) for intubation, followed by maintenance doses of rocuronium 0.1-0.2 mg/kg if necessary
10
Sugammadex 2.0 mg/kg (Rocuronium)
Sugammadex 2.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.9 mg/kg rocuronium (single-bolus IV dose) for intubation, followed by maintenance doses of rocuronium 0.1-0.2 mg/kg if necessary
10
Sugammadex 4.0 mg/kg (Rocuronium)
Sugammadex 4.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.9 mg/kg rocuronium (single-bolus IV dose) for intubation, followed by maintenance doses of rocuronium 0.1-0.2 mg/kg if necessary
11
Sugammadex 8.0 mg/kg (Rocuronium)
Sugammadex 8.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.9 mg/kg rocuronium (single-bolus IV dose) for intubation, followed by maintenance doses of rocuronium 0.1-0.2 mg/kg if necessary
10
Sugammadex 0.5 mg/kg (Vecuronium)
Sugammadex 0.5 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.1 mg/kg vecuronium (single-bolus IV dose) for intubation, followed by maintenance doses of vecuronium 0.02-0.3 mg/kg if necessary.
9
Sugammadex 1.0 mg/kg (Vecuronium)
Sugammadex 1.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.1 mg/kg vecuronium (single-bolus IV dose) for intubation, followed by maintenance doses of vecuronium 0.02-0.3 mg/kg if necessary
10
Sugammadex 2.0 mg/kg (Vecuronium)
Sugammadex 2.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.1 mg/kg vecuronium (single-bolus IV dose) for intubation, followed by maintenance doses of vecuronium 0.02-0.3 mg/kg if necessary
11
Sugammadex 4.0 mg/kg (Vecuronium)
Sugammadex 4.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.1 mg/kg vecuronium (single-bolus IV dose) for intubation, followed by maintenance doses of vecuronium 0.02-0.3 mg/kg if necessary
10
Sugammadex 8.0 mg/kg (Vecuronium)
Sugammadex 8.0 mg/kg administered as a single-bolus IV dose at 1-2 PTC after 0.1 mg/kg vecuronium (single-bolus IV dose) for intubation, followed by maintenance doses of vecuronium 0.02-0.3 mg/kg if necessary
11
Total101

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008FG009
Overall StudyLost to Follow-up0000000010
Overall StudyNot Eligible0000010000

Baseline characteristics

CharacteristicTotalSugammadex 8.0 mg/kg (Vecuronium)Sugammadex 4.0 mg/kg (Vecuronium)Sugammadex 2.0 mg/kg (Vecuronium)Sugammadex 1.0 mg/kg (Vecuronium)Sugammadex 0.5 mg/kg (Vecuronium)Sugammadex 8.0 mg/kg (Rocuronium)Sugammadex 4.0 mg/kg (Rocuronium)Sugammadex 2.0 mg/kg (Rocuronium)Sugammadex 1.0 mg/kg (Rocuronium)Sugammadex 0.5 mg/kg (Rocuronium)
Age, Continuous48 years
STANDARD_DEVIATION 11
50 years
STANDARD_DEVIATION 9
40 years
STANDARD_DEVIATION 11
54 years
STANDARD_DEVIATION 6
50 years
STANDARD_DEVIATION 14
44 years
STANDARD_DEVIATION 14
52 years
STANDARD_DEVIATION 9
51 years
STANDARD_DEVIATION 13
49 years
STANDARD_DEVIATION 6
42 years
STANDARD_DEVIATION 9
49 years
STANDARD_DEVIATION 7
American Society of Anaesthesiologists (ASA) Class
ASA Class 1
61 Participants6 Participants9 Participants7 Participants8 Participants7 Participants5 Participants6 Participants2 Participants5 Participants6 Participants
American Society of Anaesthesiologists (ASA) Class
ASA Class 2
39 Participants5 Participants1 Participants4 Participants2 Participants2 Participants5 Participants5 Participants7 Participants5 Participants3 Participants
American Society of Anaesthesiologists (ASA) Class
ASA Class 3
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
99 Participants11 Participants10 Participants11 Participants9 Participants9 Participants10 Participants11 Participants10 Participants9 Participants9 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Female
44 Participants5 Participants3 Participants4 Participants6 Participants4 Participants5 Participants6 Participants5 Participants2 Participants4 Participants
Sex: Female, Male
Male
57 Participants6 Participants7 Participants7 Participants4 Participants5 Participants5 Participants5 Participants5 Participants8 Participants5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
deaths
Total, all-cause mortality
0 / 90 / 100 / 100 / 110 / 100 / 90 / 100 / 110 / 100 / 11
other
Total, other adverse events
6 / 98 / 108 / 1010 / 118 / 106 / 96 / 107 / 116 / 108 / 11
serious
Total, serious adverse events
1 / 90 / 101 / 101 / 110 / 100 / 90 / 100 / 110 / 101 / 11

Outcome results

Primary

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.

Time frame: Up to 131:40 (min:sec)

Population: The analysis population consisted of all randomized and treated participants who had at least one post-baseline efficacy measurement, without any major or multiple minor protocol violations.

ArmMeasureValue (MEAN)Dispersion
Sugammadex 0.5 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation79.78 MinutesStandard Deviation 33.02
Sugammadex 1.0 mg/kg (Rocuroniium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation28.00 MinutesStandard Deviation 43.73
Sugammadex 2.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation3.17 MinutesStandard Deviation 1.52
Sugammadex 4.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation1.65 MinutesStandard Deviation 0.65
Sugammadex 8.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation1.13 MinutesStandard Deviation 0.33
Sugammadex 0.5 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation68.40 MinutesStandard Deviation 31.93
Sugammadex 1.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation25.12 MinutesStandard Deviation 24.87
Sugammadex 2.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation9.08 MinutesStandard Deviation 20.55
Sugammadex 4.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation3.30 MinutesStandard Deviation 3.45
Sugammadex 8.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to Recovery of the Neuromuscular Response to a Ratio of 0.9 for Train-Of-Four (TOF) Stimulation1.65 MinutesStandard Deviation 0.75
Secondary

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.

Time frame: From Screening to 7 post-operative days

Population: All randomized participants who received at least one dose of study treatment and had follow-up.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Sugammadex 0.5 mg/kg (Rocuronium)Number of Participants With An Adverse Event (AE)6 Participants
Sugammadex 1.0 mg/kg (Rocuroniium)Number of Participants With An Adverse Event (AE)8 Participants
Sugammadex 2.0 mg/kg (Rocuronium)Number of Participants With An Adverse Event (AE)8 Participants
Sugammadex 4.0 mg/kg (Rocuronium)Number of Participants With An Adverse Event (AE)10 Participants
Sugammadex 8.0 mg/kg (Rocuronium)Number of Participants With An Adverse Event (AE)8 Participants
Sugammadex 0.5 mg/kg (Vecuronium)Number of Participants With An Adverse Event (AE)6 Participants
Sugammadex 1.0 mg/kg (Vecuronium)Number of Participants With An Adverse Event (AE)6 Participants
Sugammadex 2.0 mg/kg (Vecuronium)Number of Participants With An Adverse Event (AE)7 Participants
Sugammadex 4.0 mg/kg (Vecuronium)Number of Participants With An Adverse Event (AE)6 Participants
Sugammadex 8.0 mg/kg (Vecuronium)Number of Participants With An Adverse Event (AE)8 Participants
Secondary

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.

Time frame: Up to 96:24 (min:sec)

Population: The analysis population consisted of all randomized and treated participants who had at least one post-baseline efficacy measurement, without any major protocol violation.

ArmMeasureValue (MEAN)Dispersion
Sugammadex 0.5 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.747.72 MinutesStandard Deviation 27.62
Sugammadex 1.0 mg/kg (Rocuroniium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.74.47 MinutesStandard Deviation 1.95
Sugammadex 2.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.72.17 MinutesStandard Deviation 0.97
Sugammadex 4.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.71.25 MinutesStandard Deviation 0.52
Sugammadex 8.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.70.93 MinutesStandard Deviation 0.25
Sugammadex 0.5 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.730.22 MinutesStandard Deviation 34.7
Sugammadex 1.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.74.07 MinutesStandard Deviation 2.02
Sugammadex 2.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.72.32 MinutesStandard Deviation 1.2
Sugammadex 4.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.71.65 MinutesStandard Deviation 0.67
Sugammadex 8.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.71.33 MinutesStandard Deviation 0.57
Secondary

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.

Time frame: Up to 102:25 (min:sec)

Population: The analysis population consisted of all randomized participants who were given at least one administration of sugammadex and had at least one post-baseline efficacy measurement, without any major protocol violation.

ArmMeasureValue (MEAN)Dispersion
Sugammadex 0.5 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.857.00 MinutesStandard Deviation 32.97
Sugammadex 1.0 mg/kg (Rocuroniium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.814.22 MinutesStandard Deviation 20.62
Sugammadex 2.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.82.45 MinutesStandard Deviation 1.12
Sugammadex 4.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.81.35 MinutesStandard Deviation 0.57
Sugammadex 8.0 mg/kg (Rocuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.80.98 MinutesStandard Deviation 0.32
Sugammadex 0.5 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.845.93 MinutesStandard Deviation 29.55
Sugammadex 1.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.85.10 MinutesStandard Deviation 2.7
Sugammadex 2.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.82.92 MinutesStandard Deviation 1.75
Sugammadex 4.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.82.87 MinutesStandard Deviation 3.25
Sugammadex 8.0 mg/kg (Vecuronium)Time From Start of Sugammadex Administration to a T4/T1 Recovery Ratio of 0.81.43 MinutesStandard Deviation 0.58

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026