Trial Outcomes & Findings for Comparing 4.0 mg.Kg-1 Sugammadex With Placebo in the Reversal of Profound Neuromuscular Blockade (P05767) (NCT NCT00758485)

Last Updated: 2015-08-21

Results Overview

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 (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB), with a higher ratio indicating a greater recovery from NMB. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>=0.9, the minimum acceptable ratio that indicated complete recovery from NMB. A shorter time to recovery of the T4/T1 Ratio \>=0.9 indicates a faster recovery from NMB.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

140 participants

Primary outcome timeframe

From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from ~2 minutes up to ~90 minutes)

Results posted on

2015-08-21

Participant Flow

Participants were recruited from 10 sites in Germany from November 2008 to May 2009.

Participant milestones

Participant milestones
Measure	Sugammadex Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of neuromuscular blockade (NMB) of 1-2 Post Tetanic Count (PTC) after the last dose of rocuronium	Placebo Participants receiving Placebo (0.9% sodium chloride\[NaCl\]) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Overall Study STARTED	70	70
Overall Study TREATED	69	68
Overall Study COMPLETED	69	67
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sugammadex Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of neuromuscular blockade (NMB) of 1-2 Post Tetanic Count (PTC) after the last dose of rocuronium	Placebo Participants receiving Placebo (0.9% sodium chloride\[NaCl\]) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Overall Study Lost to Follow-up	0	1
Overall Study Not Treated	1	2

Baseline Characteristics

Comparing 4.0 mg.Kg-1 Sugammadex With Placebo in the Reversal of Profound Neuromuscular Blockade (P05767)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sugammadex n=69 Participants Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of NMB of 1-2 PTC after the last dose of rocuronium.	Placebo n=68 Participants Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium.	Total n=137 Participants Total of all reporting groups
Age, Continuous	57 years STANDARD_DEVIATION 17 • n=5 Participants	57 years STANDARD_DEVIATION 14 • n=7 Participants	57 years STANDARD_DEVIATION 16 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	25 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	43 Participants n=7 Participants	91 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from ~2 minutes up to ~90 minutes)

Population: The Intent-to-Treat (ITT) Population consisted of all participants who received either Sugammadex or Placebo and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.

Outcome measures

Outcome measures
Measure	Sugammadex n=69 Participants Participants receiving 4.0 mg/kg-1 Sugammadex at a target depth of NMB of 1-2 Post Tetanic Count (PTC) after the last dose of rocuronium	Placebo n=65 Participants Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9	2.2 minutes Interval 1.9 to 2.5	89.8 minutes Interval 80.1 to 100.7

SECONDARY outcome

Timeframe: From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.7 (estimated from ~1 minute up to ~70 minutes)

Population: The ITT Population consisted of all participants who received either Sugammadex or Placebo and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.

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 (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB.

Outcome measures

Outcome measures
Measure	Sugammadex n=69 Participants Participants receiving 4.0 mg/kg-1 Sugammadex at a target depth of NMB of 1-2 Post Tetanic Count (PTC) after the last dose of rocuronium	Placebo n=65 Participants Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7	1.6 minutes Interval 1.4 to 1.8	70.1 minutes Interval 62.7 to 78.4

SECONDARY outcome

Timeframe: From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.8 (estimated from ~2 minutes up to ~80 minutes)

Outcome measures

Outcome measures
Measure	Sugammadex n=69 Participants Participants receiving 4.0 mg/kg-1 Sugammadex at a target depth of NMB of 1-2 Post Tetanic Count (PTC) after the last dose of rocuronium	Placebo n=65 Participants Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8	1.8 minutes Interval 1.6 to 2.0	78.8 minutes Interval 70.2 to 88.5

Adverse Events

Sugammadex

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sugammadex n=69 participants at risk Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of NMB of 1-2 PTC after the last dose of rocuronium	Placebo n=68 participants at risk Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Injury, poisoning and procedural complications Post Procedural Complication	1.4% 1/69 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	1.5% 1/68 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Psychiatric disorders Alcohol Withdrawal Syndrome	1.4% 1/69 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	0.00% 0/68 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Vascular disorders Lymphocele	1.4% 1/69 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	0.00% 0/68 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Injury, poisoning and procedural complications Post Procedural Haemorrhage	1.4% 1/69 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	1.5% 1/68 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Gastrointestinal disorders Diverticular Perforation	0.00% 0/69 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	1.5% 1/68 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Injury, poisoning and procedural complications Skin Laceration	0.00% 0/69 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	1.5% 1/68 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.

Other adverse events

Other adverse events
Measure	Sugammadex n=69 participants at risk Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of NMB of 1-2 PTC after the last dose of rocuronium	Placebo n=68 participants at risk Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium
Gastrointestinal disorders Constipation	8.7% 6/69 • Number of events 6 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	5.9% 4/68 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Gastrointestinal disorders Flatulence	5.8% 4/69 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	10.3% 7/68 • Number of events 7 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Gastrointestinal disorders Nausea	13.0% 9/69 • Number of events 9 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	16.2% 11/68 • Number of events 12 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Gastrointestinal disorders Vomiting	7.2% 5/69 • Number of events 5 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	7.4% 5/68 • Number of events 5 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
General disorders Pyrexia	5.8% 4/69 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	5.9% 4/68 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Injury, poisoning and procedural complications Procedural Nausea	4.3% 3/69 • Number of events 3 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	5.9% 4/68 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Injury, poisoning and procedural complications Procedural Pain	42.0% 29/69 • Number of events 30 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	47.1% 32/68 • Number of events 33 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Injury, poisoning and procedural complications Wound Complication	15.9% 11/69 • Number of events 13 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	14.7% 10/68 • Number of events 10 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Nervous system disorders Dizziness	1.4% 1/69 • Number of events 1 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	7.4% 5/68 • Number of events 5 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Nervous system disorders Headache	10.1% 7/69 • Number of events 7 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	7.4% 5/68 • Number of events 5 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.
Psychiatric disorders Sleep Disorder	5.8% 4/69 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.	5.9% 4/68 • Number of events 4 • Up to 7 days after administration of IMP The All Subjects Treated Population consisted of all randomized participants who received IMP.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place