Trial Outcomes & Findings for Sugammadex Hypersensitivity Study (Study P06042) (NCT NCT00988065)
NCT ID: NCT00988065
Last Updated: 2019-01-30
Results Overview
Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists \& allergists/immunologists) for blinded review and determination of adjudicated hypersensitivity \&/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity at any dose (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) were compared between the 3 treatment groups.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
448 participants
Primary outcome timeframe
Day 8, Day 36, and Day 78 of the study
Results posted on
2019-01-30
Participant Flow
A total of 480 participants received a single-blind placebo dose 7 days prior to randomization. Of these 480 participants, 448 were randomized to double-blind treatment.
Participant milestones
| Measure |
Sugammadex 4 mg/kg
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
148
|
150
|
150
|
|
Overall Study
Received First Randomized Dose
|
148
|
150
|
150
|
|
Overall Study
Received Second Randomized Dose
|
139
|
135
|
145
|
|
Overall Study
Received Third Randomized Dose
|
135
|
127
|
135
|
|
Overall Study
COMPLETED
|
135
|
127
|
135
|
|
Overall Study
NOT COMPLETED
|
13
|
23
|
15
|
Reasons for withdrawal
| Measure |
Sugammadex 4 mg/kg
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
10
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
2
|
|
Overall Study
Subject withdrew consent
|
3
|
5
|
2
|
|
Overall Study
Noncompliance with protocol
|
5
|
6
|
9
|
Baseline Characteristics
Sugammadex Hypersensitivity Study (Study P06042)
Baseline characteristics by cohort
| Measure |
Sugammadex 4 mg/kg
n=148 Participants
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 Participants
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 Participants
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Total
n=448 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
34.4 years
STANDARD_DEVIATION 10.6 • n=99 Participants
|
33.2 years
STANDARD_DEVIATION 10.2 • n=107 Participants
|
33.8 years
STANDARD_DEVIATION 10.8 • n=206 Participants
|
33.8 years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=99 Participants
|
73 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
218 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
78 Participants
n=99 Participants
|
77 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
230 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Day 8, Day 36, and Day 78 of the studyPopulation: All-Subjects as treated (i.e., who received at least one dose of randomized study medication).
Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists \& allergists/immunologists) for blinded review and determination of adjudicated hypersensitivity \&/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity at any dose (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) were compared between the 3 treatment groups.
Outcome measures
| Measure |
Sugammadex 4 mg/kg
n=148 Participants
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 Participants
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 Participants
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo.
|
0.7 percentage of participants
Interval 0.0 to 3.7
|
4.7 percentage of participants
Interval 1.9 to 9.4
|
0 percentage of participants
Interval 0.0 to 2.4
|
SECONDARY outcome
Timeframe: Day 8, Day 36, and Day 78 of the studyPopulation: All-Subjects as treated (i.e., who received at least one dose of randomized study medication).
The Adjudication Committee evaluated each case to determine whether the subject's hypersensitivity sign/symptoms fulfilled the definition of anaphylaxis according to the criteria defined by the Symposium on the Definition and Management of Anaphylaxis as described by Sampson et al. (J Allergy Clin Immunol 2006; 117:391-7). The percentages of subjects who had adjudicated anaphylaxis according to the Sampson Criteria at any dose (dose 1 \[\~Day 8\], dose 2 \[\~Day 36\], or dose 3 \[Day \~78\]) were compared between the 3 treatment groups.
Outcome measures
| Measure |
Sugammadex 4 mg/kg
n=148 Participants
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 Participants
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 Participants
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo.
|
0 percentage of participants
Interval 0.0 to 2.5
|
0.7 percentage of participants
Interval 0.0 to 3.7
|
0 percentage of participants
Interval 0.0 to 2.4
|
SECONDARY outcome
Timeframe: Day 8, Day 36, and Day 78 of the studyPopulation: All-Subjects as treated (i.e., who received at least one dose of randomized study medication).
The Adjudication Committee evaluated each case to determine anaphylaxis according to the criteria put forth by the guidelines of the Brighton Collaboration Anaphylaxis Working Group as described by Rüggeberg et al. (Vaccine 2007; 25:5675-5684). Level 1 represents the highest level of certainty of anaphylaxis and level 3 the lowest level of certainty. The percentages of subjects who had adjudicated anaphylaxis according to the Rüggeberg Criteria at any dose (dose 1 \[\~Day 8\], dose 2 \[\~Day 36\], or dose 3 \[Day \~78\]) were compared between the 3 treatment groups.
Outcome measures
| Measure |
Sugammadex 4 mg/kg
n=148 Participants
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 Participants
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 Participants
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
The Percentage of Participants With Each of the 3 Levels of Diagnostic Certainty of Adjudicated Anaphylaxis According to the Definition by Rüggeberg et al., for Each Sugammadex Dose Group and Placebo.
Level 1
|
0 percentage of participants
|
0.7 percentage of participants
|
0 percentage of participants
|
|
The Percentage of Participants With Each of the 3 Levels of Diagnostic Certainty of Adjudicated Anaphylaxis According to the Definition by Rüggeberg et al., for Each Sugammadex Dose Group and Placebo.
Level 2
|
0 percentage of participants
|
1.3 percentage of participants
|
0 percentage of participants
|
|
The Percentage of Participants With Each of the 3 Levels of Diagnostic Certainty of Adjudicated Anaphylaxis According to the Definition by Rüggeberg et al., for Each Sugammadex Dose Group and Placebo.
Level 3
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
The Percentage of Participants With Each of the 3 Levels of Diagnostic Certainty of Adjudicated Anaphylaxis According to the Definition by Rüggeberg et al., for Each Sugammadex Dose Group and Placebo.
Level 1 or Level 2
|
0 percentage of participants
|
2.0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 8, Day 36, and Day 78 of the studyPopulation: All-Subjects as treated, per dose (i.e. who received the corresponding dose of randomized study medication).
Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists \& allergists/immunologists) for blinded review \& determination of adjudicated hypersensitivity \&/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) are presented for each of the 3 treatment arms for each dose.
Outcome measures
| Measure |
Sugammadex 4 mg/kg
n=148 Participants
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 Participants
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 Participants
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo.
3rd randomized dose (n=135; n=127; n=135)
|
0 percentage of participants
|
0.8 percentage of participants
|
0 percentage of participants
|
|
The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo.
after any randomized dose
|
0.7 percentage of participants
|
4.7 percentage of participants
|
0 percentage of participants
|
|
The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo.
1st randomized dose
|
0.7 percentage of participants
|
4.0 percentage of participants
|
0 percentage of participants
|
|
The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo.
2nd randomized dose (n=139; n=135; n=145)
|
0.7 percentage of participants
|
1.5 percentage of participants
|
0 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication.Population: All-Subjects as treated (i.e., who received at least one dose of randomized study medication).
All adverse events from the study were reviewed for potential safety signals. The reported incidences suggestive of a dose-dependent trend and with a frequency threshold above 5% (including both serious and non-serious adverse events) are presented.
Outcome measures
| Measure |
Sugammadex 4 mg/kg
n=148 Participants
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 Participants
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 Participants
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
Percentage of Participants With an Adverse Event Suggestive of a Dose-dependent Trend That Also Exceeds a Frequency Threshold Above 5% in Any Treatment Arm (Including Both Serious and Non-serious Adverse Events).
Flushing
|
1.4 percentage of participants
|
5.3 percentage of participants
|
0.7 percentage of participants
|
|
Percentage of Participants With an Adverse Event Suggestive of a Dose-dependent Trend That Also Exceeds a Frequency Threshold Above 5% in Any Treatment Arm (Including Both Serious and Non-serious Adverse Events).
Nausea
|
5.4 percentage of participants
|
16.0 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With an Adverse Event Suggestive of a Dose-dependent Trend That Also Exceeds a Frequency Threshold Above 5% in Any Treatment Arm (Including Both Serious and Non-serious Adverse Events).
Dysgeusia
|
3.4 percentage of participants
|
21.3 percentage of participants
|
0 percentage of participants
|
Adverse Events
Sugammadex 4 mg/kg
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Sugammadex 16 mg/kg
Serious events: 2 serious events
Other events: 64 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sugammadex 4 mg/kg
n=148 participants at risk
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 participants at risk
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 participants at risk
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Immune system disorders
Anaphylactic shock
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Metabolism and nutrition disorders
Type 1 diabetes mellitus
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Vascular disorders
Flushing
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Vascular disorders
Hypotension
|
0.00%
0/148 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.67%
1/150 • Number of events 1 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
Other adverse events
| Measure |
Sugammadex 4 mg/kg
n=148 participants at risk
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Sugammadex 16 mg/kg
n=150 participants at risk
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
Placebo
n=150 participants at risk
Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.4%
8/148 • Number of events 11 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
16.0%
24/150 • Number of events 34 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
1.3%
2/150 • Number of events 3 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Infections and infestations
Nasopharyngitis
|
4.1%
6/148 • Number of events 6 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
6.7%
10/150 • Number of events 10 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
8.7%
13/150 • Number of events 15 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Nervous system disorders
Dysgeusia
|
3.4%
5/148 • Number of events 8 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
21.3%
32/150 • Number of events 43 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
0.00%
0/150 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Nervous system disorders
Headache
|
11.5%
17/148 • Number of events 20 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
12.7%
19/150 • Number of events 23 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
10.7%
16/150 • Number of events 16 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.0%
3/148 • Number of events 3 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
2.7%
4/150 • Number of events 4 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
6.0%
9/150 • Number of events 9 • Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Investigator may not publish/publicly present interim results without prior consent of Sponsor. Any materials that report results of the study must be sent to Sponsor 45 days prior to submission for publication/presentation. Sponsor has right to review and comment. In case of any disagreements concerning appropriateness of the materials, investigator and Sponsor must meet to make a good faith effort to discuss/resolve the issues or disagreement, prior to submission for publication/presentation.
- Publication restrictions are in place
Restriction type: OTHER