A Bridging Trial Comparing Sugammadex (Org 25969) at Reappearance of T2 in Japanese and Caucasian Participants. Part B: Caucasian Participants (P05971)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00552617
Collaborator
(none)
100
10
11.3
Study Details
Study Description
Brief Summary
The objective of the trial was to establish the dose-response relation of sugammadex (Org 25969) given as a reversal agent of rocuronium or vecuronium at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control first twitch, T1) during sevoflurane anesthesia for Caucasian participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
For most surgical procedures a depth of neuromuscular block of 1-2 twitches after TOF-stimulation is sufficient to avoid unwanted muscular activity. At reappearance of T2, the anesthesiologist might decide to either give (another) maintenance dose of rocuronium or vecuronium when surgery continues, to await spontaneous recovery of neuromuscular block or to reverse the neuromuscular block. Sugammadex has been shown in previous trials to greatly reduce the time to full recovery when administered at reappearance of T2, both after rocuronium- and vecuronium induced neuromuscular blockade. The current trial P05971 was conducted in Europe and set up to establish the dose response relationship of sugammadex given during sevoflurane anesthesia at reappearance of T2 after rocuronium or vecuronium in Caucasian participants. In addition to recovery time, also pharmacokinetics and safety of sugammadex were to be evaluated.
Study Design
Study Type:
Interventional
Actual Enrollment
:
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multi-Center, Randomized, Open-Label, Prospective Bridging, Parallel Dose-Finding Trial Comparing Efficacy, Safety and Pharmacokinetics of 4 Doses of Org 25969 and Placebo Administered at Reappearance of T2 After Rocuronium or Vecuronium in Japanese and Caucasian Subjects. Part B: Caucasian Subjects
Actual Study Start Date
:
Sep 20, 2005
Actual Primary Completion Date
:
Aug 31, 2006
Actual Study Completion Date
:
Aug 31, 2006
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Rocuronium + Placebo After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. |
Drug: Placebo
After induction of anesthesia an intubation dose of NMBA was administered IV: either 0.9 mg/kg rocuronium (arm 1) or 0.1 mg/kg vecuronium (arm 6).
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 Placebo IV was administered
Drug: Rocuronium
After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.
Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.
|
| Experimental: Rocuronium + 0.5 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Rocuronium
After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.
Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.
|
| Experimental: Rocuronium + 1.0 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Rocuronium
After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.
Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.
|
| Experimental: Rocuronium + 2.0 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Rocuronium
After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.
Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.
|
| Experimental: Rocuronium + 4.0 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Rocuronium
After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.
Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.
|
| Placebo Comparator: Vecuronium + Placebo After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. |
Drug: Placebo
After induction of anesthesia an intubation dose of NMBA was administered IV: either 0.9 mg/kg rocuronium (arm 1) or 0.1 mg/kg vecuronium (arm 6).
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 Placebo IV was administered
Drug: Vecuronium
After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.
|
| Experimental: Vecuronium + 0.5 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Vecuronium
After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.
|
| Experimental: Vecuronium + 1.0 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Vecuronium
After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.
|
| Experimental: Vecuronium + 2.0 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Vecuronium
After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.
|
| Experimental: Vecuronium + 4.0 mg/kg Sugammadex After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
Drug: Sugammadex
After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.
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 4 mg/kg IV was administered
Other Names:
Drug: Vecuronium
After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.
|
Outcome Measures
Primary Outcome Measures
- Time From Start of Administration of Sugammadex or Placebo to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 [Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.9 (up to 24 hours)]
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 Outcome Measures
- Time From Start of Administration of Sugammadex or Placebo to Recovery of the T4/T1 Ratio to 0.7 [Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.7 (up to 24 hours)]
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 Administration of Sugammadex or Placebo to Recovery of the T4/T1 Ratio to 0.8 [Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.8 (up to 24 hours)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Is of American Society of Anesthesiologists (ASA) class 1 - 3;
-
Is at least 20 years but under 65 years of age;
-
Caucasian participants;
-
Is scheduled for elective surgery requiring muscle relaxation in supine position and under sevoflurane anesthesia with an anticipated duration of about 1.5-3 hours;
-
Has given written informed consent.
Exclusion criteria:
-
Participants in whom a difficult intubation because of anatomical malformations was expected;
-
Is known or suspected to have neuromuscular disorders impairing neuromuscular blocking (NMB) and/or significant renal dysfunction (for example a creatinine level > 1.6 mg/dl) and/or severe hepatic dysfunction.
-
Is known or suspected to have a (family) history of malignant hyperthermia;
-
Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
-
Is receiving medication expected to interfere with the rocuronium or vecuronium given in this trial, based on the dose and time of administration;
-
Females who were pregnant;
-
Females of childbearing potential not using birth control or using only oral contraception as birth control;
-
Was breast-feeding;
-
Has already participated in P05971, or in another trial with sugammadex;
-
Has participated in another clinical trial, not preapproved by the Sponsor, within 6 months of entering into P05971.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00552617
Other Study ID Numbers:
- P05971
- 19.4.208B
- MK-8616-035
- 2005-001133-15
First Posted:
Nov 2, 2007
Last Update Posted:
Nov 25, 2019
Last Verified:
Nov 1, 2019
Study Results
Participant Flow
| Recruitment Details | Caucasian participants who had a surgical procedure using a general anesthesia of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block were enrolled in this study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Period Title: Overall Study | ||||||||||
| STARTED | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Treated | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 9 |
| COMPLETED | 10 | 10 | 9 | 9 | 10 | 8 | 10 | 10 | 8 | 9 |
| NOT COMPLETED | 0 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | Total of all reporting groups |
| Overall Participants | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 9 | 98 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||||
| Mean (Standard Deviation) [Years] |
50
(7)
|
52
(7)
|
50
(9)
|
49
(8)
|
49
(13)
|
48
(10)
|
47
(9)
|
46
(9)
|
45
(10)
|
47
(10)
|
48
(9)
|
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
8
80%
|
8
80%
|
7
77.8%
|
5
50%
|
6
60%
|
8
80%
|
7
70%
|
7
70%
|
7
70%
|
7
77.8%
|
70
71.4%
|
| Male |
2
20%
|
2
20%
|
2
22.2%
|
5
50%
|
4
40%
|
2
20%
|
3
30%
|
3
30%
|
3
30%
|
2
22.2%
|
28
28.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
10
100%
|
10
100%
|
9
100%
|
10
100%
|
10
100%
|
10
100%
|
10
100%
|
10
100%
|
10
100%
|
9
100%
|
98
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Time From Start of Administration of Sugammadex or Placebo 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 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 | Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.9 (up to 24 hours) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received sugammadex or placebo; without any protocol violations, and who had at least one post baseline efficacy measurement, who had a TOF trace, had a reliable TOF trace, and where drug administration did not interfere with the effect of rocuronium or vecuronium. |
| Arm/Group Title | Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Measure Participants | 7 | 8 | 8 | 9 | 8 | 8 | 9 | 10 | 7 | 9 |
| Mean (Standard Deviation) [Minutes] |
96.30
(33.13)
|
16.30
(20.60)
|
4.62
(5.97)
|
1.43
(0.50)
|
1.50
(0.40)
|
79.02
(25.97)
|
35.50
(42.13)
|
5.07
(2.38)
|
3.42
(1.85)
|
3.03
(2.18)
|
| Title | Time From Start of Administration of Sugammadex or Placebo 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 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 | Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.7 (up to 24 hours) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received sugammadex or placebo; without any protocol violations, and who had at least one post baseline efficacy measurement, who had a TOF trace, had a reliable TOF trace, and where drug administration did not interfere with the effect of rocuronium or vecuronium. |
| Arm/Group Title | Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Measure Participants | 7 | 10 | 8 | 9 | 9 | 8 | 10 | 10 | 9 | 9 |
| Mean (Standard Deviation) [Minutes] |
65.67
(35.73)
|
3.08
(2.25)
|
2.08
(1.12)
|
1.12
(0.40)
|
1.02
(0.12)
|
58.12
(21.90)
|
12.57
(24.48)
|
2.35
(0.48)
|
2.00
(1.25)
|
1.70
(0.55)
|
| Title | Time From Start of Administration of Sugammadex or Placebo 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 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 | Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.8 (up to 24 hours) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received sugammadex or placebo; without any protocol violations, and who had at least one post baseline efficacy measurement, who had a TOF trace, had a reliable TOF trace, and where drug administration did not interfere with the effect of rocuronium or vecuronium. |
| Arm/Group Title | Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Measure Participants | 7 | 9 | 8 | 9 | 9 | 8 | 10 | 10 | 9 | 9 |
| Mean (Standard Deviation) [Minutes] |
75.85
(36.65)
|
6.25
(9.12)
|
2.62
(1.80)
|
1.28
(0.42)
|
1.15
(0.25)
|
64.33
(21.72)
|
25.65
(35.40)
|
3.10
(0.88)
|
5.83
(11.43)
|
2.12
(0.80)
|
Adverse Events
| Time Frame | Up to 7 days after sugammadex or placebo treatment | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All randomized participants who received study treatment | |||||||||||||||||||
| Arm/Group Title | Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex | ||||||||||
| Arm/Group Description | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/10 (10%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/10 (10%) | 0/10 (0%) | 0/10 (0%) | 2/10 (20%) | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Large intestine perforation | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||
| Bladder tamponade | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Urinary bladder haemorrhage | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Pulmonary embolism | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Rocuronium + Placebo | Rocuronium + 0.5 mg/kg Sugammadex | Rocuronium + 1.0 mg/kg Sugammadex | Rocuronium + 2.0 mg/kg Sugammadex | Rocuronium + 4.0 mg/kg Sugammadex | Vecuronium + Placebo | Vecuronium + 0.5 mg/kg Sugammadex | Vecuronium + 1.0 mg/kg Sugammadex | Vecuronium + 2.0 mg/kg Sugammadex | Vecuronium + 4.0 mg/kg Sugammadex | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/10 (90%) | 10/10 (100%) | 6/9 (66.7%) | 10/10 (100%) | 10/10 (100%) | 8/10 (80%) | 10/10 (100%) | 6/10 (60%) | 9/10 (90%) | 7/9 (77.8%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Coagulopathy | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Haemolysis | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||
| Vertigo | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 2/9 (22.2%) | 2 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal distension | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Abdominal pain | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/9 (11.1%) | 1 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Abdominal pain upper | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Constipation | 1/10 (10%) | 1 | 3/10 (30%) | 3 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Diarrhoea | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 1/9 (11.1%) | 1 |
| Dyspepsia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Eructation | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Flatulence | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Infrequent bowel movements | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Nausea | 3/10 (30%) | 3 | 5/10 (50%) | 5 | 3/9 (33.3%) | 3 | 6/10 (60%) | 7 | 4/10 (40%) | 4 | 3/10 (30%) | 3 | 4/10 (40%) | 5 | 1/10 (10%) | 1 | 2/10 (20%) | 2 | 4/9 (44.4%) | 4 |
| Paraesthesia oral | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Vomiting | 2/10 (20%) | 2 | 4/10 (40%) | 4 | 1/9 (11.1%) | 1 | 2/10 (20%) | 2 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 3/10 (30%) | 3 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 4/9 (44.4%) | 4 |
| General disorders | ||||||||||||||||||||
| Asthenia | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Catheter related complication | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Chills | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Feeling drunk | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hypothermia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Infusion site swelling | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Non-cardiac chest pain | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Oedema | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Pain | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Pyrexia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/9 (11.1%) | 1 |
| Infections and infestations | ||||||||||||||||||||
| Candidiasis | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Ureteritis | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Urinary tract infection | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Airway complication of anaesthesia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Anaesthetic complication | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Operative haemorrhage | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Post procedural complication | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Post procedural nausea | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 2/10 (20%) | 3 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Post procedural vomiting | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Postoperative constipation | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Procedural complication | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Procedural hypertension | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Procedural hypotension | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Procedural pain | 4/10 (40%) | 4 | 5/10 (50%) | 5 | 3/9 (33.3%) | 3 | 6/10 (60%) | 6 | 6/10 (60%) | 7 | 4/10 (40%) | 4 | 2/10 (20%) | 2 | 3/10 (30%) | 3 | 4/10 (40%) | 6 | 3/9 (33.3%) | 3 |
| Wound complication | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Wound secretion | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Investigations | ||||||||||||||||||||
| Beta 2 microglobulin increased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Beta 2 microglobulin urine increased | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Beta-N-acetyl-D-glucosaminidase increased | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Blood bilirubin increased | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Blood glucose increased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Body temperature increased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Haematocrit decreased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Haemoglobin decreased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Haptoglobin decreased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Heart rate increased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Lymphocyte count decreased | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Neutrophil count increased | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Oxygen saturation decreased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Protein total decreased | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Gout | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hyperglycaemia | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Hypoalbuminaemia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hypocalcaemia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Metabolic acidosis | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Back pain | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Muscle spasms | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Muscular weakness | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 2 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Musculoskeletal chest pain | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Neck pain | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Shoulder pain | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/9 (11.1%) | 1 |
| Nervous system disorders | ||||||||||||||||||||
| Dizziness postural | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Dysgeusia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Headache | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 3/10 (30%) | 4 | 2/10 (20%) | 2 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Migraine | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Paraesthesia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Paralysis | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||
| Agitation | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Breath holding | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Confusional state | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Initial insomnia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Insomnia | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Sleep disorder | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||
| Bladder spasm | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Bladder tamponade | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Haematuria | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Ketonuria | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Microalbuminuria | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Micturition urgency | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Oliguria | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Polyuria | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 |
| Urinary incontinence | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Urinary retention | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Urinary tract obstruction | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||
| Genital pruritus female | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Cough | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 |
| Dysphonia | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Dyspnoea | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hiccups | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hypoventilation | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Pharyngolaryngeal pain | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Hyperhidrosis | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Rash | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||
| Haemodynamic instability | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hypertension | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Hypotension | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
| Thrombophlebitis superficial | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 1/10 (10%) | 1 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Any scientific paper, presentation, or other communication concerning this clinical trial will first be submitted to the Sponsor, at least six weeks ahead of estimated publication or presentation, for written consent, which shall not be withheld unreasonably.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00552617
Other Study ID Numbers:
- P05971
- 19.4.208B
- MK-8616-035
- 2005-001133-15
First Posted:
Nov 2, 2007
Last Update Posted:
Nov 25, 2019
Last Verified:
Nov 1, 2019