Trial Outcomes & Findings for Comparison of 2.0 mg/kg Sugammadex and Neostigmine at Reappearance of T2 in Chinese and European Subjects (Study 19.4.324)(P05768AM1)(COMPLETED) (NCT NCT00825812)

Last Updated: 2015-11-02

Results Overview

Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation was to continue until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached \>= 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. The primary analysis was the comparison between sugammadex \& neostigmine among Chinese subjects; other comparisons were secondary.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

308 participants

Primary outcome timeframe

start of administration of sugammadex/neostigmine to recovery from neuromuscular blockade

Results posted on

2015-11-02

Participant Flow

308 participants were randomized

Participant milestones

Participant milestones
Measure	Sugammadex in Caucasian Subjects At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Caucasian Subjects At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.
Overall Study STARTED	29	32	126	121
Overall Study TREATED	29	31	120	111
Overall Study COMPLETED	29	31	120	111
Overall Study NOT COMPLETED	0	1	6	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Neostigmine in Caucasian Subjects At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.
Overall Study Never entered follow up	0	0	1
Overall Study Adverse Event	0	0	1
Overall Study Subject withdrew consent	0	3	2
Overall Study Non-compliance with protocol	0	0	1
Overall Study Administrative	1	3	5

Baseline Characteristics

Comparison of 2.0 mg/kg Sugammadex and Neostigmine at Reappearance of T2 in Chinese and European Subjects (Study 19.4.324)(P05768AM1)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sugammadex in Caucasian Subjects n=29 Participants At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Caucasian Subjects n=31 Participants At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects n=120 Participants At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects n=111 Participants At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Total n=291 Participants Total of all reporting groups
Age, Continuous	52.0 years FULL_RANGE 10.3 • n=99 Participants	51.9 years FULL_RANGE 7.3 • n=107 Participants	39.9 years FULL_RANGE 10.8 • n=206 Participants	39.4 years FULL_RANGE 10.8 • n=7 Participants	42.2 years n=31 Participants
Sex: Female, Male Female	25 Participants n=99 Participants	28 Participants n=107 Participants	78 Participants n=206 Participants	86 Participants n=7 Participants	217 Participants n=31 Participants
Sex: Female, Male Male	4 Participants n=99 Participants	3 Participants n=107 Participants	42 Participants n=206 Participants	25 Participants n=7 Participants	74 Participants n=31 Participants

PRIMARY outcome

Timeframe: start of administration of sugammadex/neostigmine to recovery from neuromuscular blockade

Population: The Full Analysis Set (FAS) population included all subjects who received randomized treatment and had at least one efficacy measurement. In the event of missing data, imputed data were used for analysis. 291 subjects received IMP, of whom two had no efficacy measurements at all. Hence the FAS consisted of 289 subjects.

Outcome measures

Outcome measures
Measure	Sugammadex in Caucasian Subjects n=29 Participants At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Caucasian Subjects n=30 Participants At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects n=119 Participants At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects n=111 Participants At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.
Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9.	1.4 minutes Interval 1.3 to 1.5	6.7 minutes Interval 5.5 to 8.0	1.6 minutes Interval 1.5 to 1.7	9.1 minutes Interval 8.0 to 10.3

SECONDARY outcome

Timeframe: start of administration of sugammadex/neostigmine to recovery from neuromuscular blockade

Population: The Full Analysis Set population included all subjects who received randomized treatment and had at least one efficacy measurement. In the event of missing data, imputed data were used for analysis.

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. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade.

Outcome measures

Outcome measures
Measure	Sugammadex in Caucasian Subjects n=29 Participants At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Caucasian Subjects n=30 Participants At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects n=119 Participants At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects n=111 Participants At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 and 0.8. Recovery of T4/T1 ratio to 0.8	1.2 minutes Interval 1.1 to 1.3	4.6 minutes Interval 4.0 to 5.4	1.3 minutes Interval 1.2 to 1.4	6.0 minutes Interval 5.4 to 6.7
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 and 0.8. Recovery of T4/T1 ratio to 0.7	1.0 minutes Interval 0.9 to 1.1	3.4 minutes Interval 3.0 to 3.8	1.1 minutes Interval 1.1 to 1.2	4.4 minutes Interval 4.0 to 4.9

Adverse Events

Sugammadex in Caucasian Subjects

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Neostigmine in Caucasian Subjects

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Sugammadex in Chinese Subjects

Serious events: 0 serious events

Other events: 73 other events

Deaths: 0 deaths

Neostigmine in Chinese Subjects

Serious events: 1 serious events

Other events: 84 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sugammadex in Caucasian Subjects n=29 participants at risk At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Caucasian Subjects n=31 participants at risk At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects n=120 participants at risk At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects n=111 participants at risk At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.
Infections and infestations Enterococcal bacteraemia	0.00% 0/29	3.2% 1/31 • Number of events 1	0.00% 0/120	0.00% 0/111
Injury, poisoning and procedural complications Anastomotic leak	0.00% 0/29	3.2% 1/31 • Number of events 1	0.00% 0/120	0.00% 0/111
Injury, poisoning and procedural complications Incision site haemorrhage	0.00% 0/29	0.00% 0/31	0.00% 0/120	0.90% 1/111 • Number of events 1

Other adverse events

Other adverse events
Measure	Sugammadex in Caucasian Subjects n=29 participants at risk At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Caucasian Subjects n=31 participants at risk At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Sugammadex in Chinese Subjects n=120 participants at risk At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Neostigmine in Chinese Subjects n=111 participants at risk At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.
Gastrointestinal disorders Abdominal pain	3.4% 1/29 • Number of events 2	3.2% 1/31 • Number of events 1	0.83% 1/120 • Number of events 1	5.4% 6/111 • Number of events 6
Gastrointestinal disorders Abdominal pain upper	0.00% 0/29	6.5% 2/31 • Number of events 2	5.0% 6/120 • Number of events 6	1.8% 2/111 • Number of events 2
Gastrointestinal disorders Nausea	13.8% 4/29 • Number of events 4	22.6% 7/31 • Number of events 9	8.3% 10/120 • Number of events 11	11.7% 13/111 • Number of events 13
Gastrointestinal disorders Vomiting	0.00% 0/29	0.00% 0/31	9.2% 11/120 • Number of events 11	9.9% 11/111 • Number of events 11
General disorders Fatigue	6.9% 2/29 • Number of events 2	0.00% 0/31	0.00% 0/120	0.00% 0/111
General disorders Pyrexia	6.9% 2/29 • Number of events 2	3.2% 1/31 • Number of events 1	13.3% 16/120 • Number of events 17	14.4% 16/111 • Number of events 16
General disorders Sensation of foreign body	0.00% 0/29	0.00% 0/31	6.7% 8/120 • Number of events 8	3.6% 4/111 • Number of events 4
Injury, poisoning and procedural complications Anaesthetic complication cardiac	0.00% 0/29	16.1% 5/31 • Number of events 5	0.83% 1/120 • Number of events 2	6.3% 7/111 • Number of events 7
Injury, poisoning and procedural complications Incision site pain	0.00% 0/29	0.00% 0/31	23.3% 28/120 • Number of events 28	23.4% 26/111 • Number of events 26
Injury, poisoning and procedural complications Procedural hypotension	20.7% 6/29 • Number of events 8	45.2% 14/31 • Number of events 20	0.83% 1/120 • Number of events 1	0.00% 0/111
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/29	0.00% 0/31	3.3% 4/120 • Number of events 4	6.3% 7/111 • Number of events 7
Injury, poisoning and procedural complications Procedural pain	44.8% 13/29 • Number of events 20	38.7% 12/31 • Number of events 15	8.3% 10/120 • Number of events 10	9.0% 10/111 • Number of events 10
Injury, poisoning and procedural complications Procedural vomiting	0.00% 0/29	0.00% 0/31	3.3% 4/120 • Number of events 4	6.3% 7/111 • Number of events 7
Injury, poisoning and procedural complications Wound complication	10.3% 3/29 • Number of events 3	9.7% 3/31 • Number of events 4	2.5% 3/120 • Number of events 3	1.8% 2/111 • Number of events 2
Nervous system disorders Dizziness	6.9% 2/29 • Number of events 2	0.00% 0/31	9.2% 11/120 • Number of events 11	19.8% 22/111 • Number of events 23
Nervous system disorders Headache	3.4% 1/29 • Number of events 1	6.5% 2/31 • Number of events 2	4.2% 5/120 • Number of events 5	5.4% 6/111 • Number of events 6
Psychiatric disorders Insomnia	6.9% 2/29 • Number of events 2	9.7% 3/31 • Number of events 3	1.7% 2/120 • Number of events 2	0.90% 1/111 • Number of events 1
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/29	0.00% 0/31	4.2% 5/120 • Number of events 5	8.1% 9/111 • Number of events 9
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.00% 0/29	0.00% 0/31	4.2% 5/120 • Number of events 5	9.0% 10/111 • Number of events 10
Surgical and medical procedures Hypotensive anaesthesia procedure	3.4% 1/29 • Number of events 1	6.5% 2/31 • Number of events 2	0.00% 0/120	0.00% 0/111

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI must not publish/publicly present any interim results without prior written consent of sponsor. The PI must provide copies of material for sponsor to review, 45 days prior to submission for publication/presentation. The sponsor may review/comment. If the parties disagree on the appropriateness of the data analysis and presentation, the PI must agree to meet prior to submission for publication/presentation to make good faith efforts to discuss and resolve any issues or disagreement.
Publication restrictions are in place

Restriction type: OTHER