Trial Outcomes & Findings for A Study to Evaluate the Incidence of Hypersensitivity After Administration of Sugammadex in Healthy Participants (MK-8616-101) (NCT NCT02028065)
NCT ID: NCT02028065
Last Updated: 2019-04-03
Results Overview
The investigator or designated clinician performed a targeted hypersensitivity assessment (THA) in each participant at 0.5, 4 and 24 hours after each dose for each dosing period. The THA could also be performed at other times if possible hypersensitivity signs were observed. The THA included elicitation of symptoms as well as examination of the participant, covering neurologic, pulmonary, cardiovascular, gastrointestinal and dermatologic domains. Each potential hypersensitivity case identified by the presence of any sign or symptom in a pre-defined list of hypersensitivity signs and symptoms that were found through the THA was reviewed by an independent, blinded adjudication committee, which determined whether the referred case was a case of hypersensitivity (yes/no). In addition, all adverse events (AEs) occurring in study were reviewed for terms associated with hypersensitivity or anaphylaxis, and could also result in referral to the adjudication committee for evaluation.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
382 participants
Primary outcome timeframe
Up to approximately 28 days after last dose (approximately 14 weeks)
Results posted on
2019-04-03
Participant Flow
One participant who was randomized to sugammadex 16 mg/kg instead received 3 doses of placebo and completed study. This participant appears in sugammadex 16 mg/kg column in Participant Flow period "Randomization through Start Treatment" and in placebo column in period "Treatment through Study Completion."
Participant milestones
| Measure |
Placebo
Administration of 3 single intravenous (IV) doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
|---|---|---|---|
|
Randomization Through Start Treatment
STARTED
|
76
|
154
|
152
|
|
Randomization Through Start Treatment
COMPLETED
|
75
|
151
|
149
|
|
Randomization Through Start Treatment
NOT COMPLETED
|
1
|
3
|
3
|
|
Treatment Through Study Completion
STARTED
|
76
|
151
|
148
|
|
Treatment Through Study Completion
Received First Dose
|
76
|
151
|
148
|
|
Treatment Through Study Completion
Received Second Dose
|
69
|
140
|
138
|
|
Treatment Through Study Completion
Received Third Dose
|
64
|
136
|
134
|
|
Treatment Through Study Completion
COMPLETED
|
64
|
136
|
134
|
|
Treatment Through Study Completion
NOT COMPLETED
|
12
|
15
|
14
|
Reasons for withdrawal
| Measure |
Placebo
Administration of 3 single intravenous (IV) doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
|---|---|---|---|
|
Randomization Through Start Treatment
Not treated
|
1
|
3
|
3
|
|
Treatment Through Study Completion
Lost to Follow-up
|
2
|
4
|
6
|
|
Treatment Through Study Completion
Physician Decision
|
1
|
0
|
0
|
|
Treatment Through Study Completion
Protocol Violation
|
1
|
4
|
0
|
|
Treatment Through Study Completion
Withdrawal by Subject
|
5
|
4
|
3
|
|
Treatment Through Study Completion
Adverse Event
|
3
|
3
|
5
|
Baseline Characteristics
A Study to Evaluate the Incidence of Hypersensitivity After Administration of Sugammadex in Healthy Participants (MK-8616-101)
Baseline characteristics by cohort
| Measure |
Placebo
n=76 Participants
Administration of 3 single IV doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
n=151 Participants
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
n=148 Participants
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Total
n=375 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
38 years
STANDARD_DEVIATION 10 • n=5 Participants
|
39 years
STANDARD_DEVIATION 11 • n=7 Participants
|
38 years
STANDARD_DEVIATION 11 • n=5 Participants
|
38 years
STANDARD_DEVIATION 11 • n=4 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=5 Participants
|
83 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
198 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
177 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 28 days after last dose (approximately 14 weeks)Population: APaT - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
The investigator or designated clinician performed a targeted hypersensitivity assessment (THA) in each participant at 0.5, 4 and 24 hours after each dose for each dosing period. The THA could also be performed at other times if possible hypersensitivity signs were observed. The THA included elicitation of symptoms as well as examination of the participant, covering neurologic, pulmonary, cardiovascular, gastrointestinal and dermatologic domains. Each potential hypersensitivity case identified by the presence of any sign or symptom in a pre-defined list of hypersensitivity signs and symptoms that were found through the THA was reviewed by an independent, blinded adjudication committee, which determined whether the referred case was a case of hypersensitivity (yes/no). In addition, all adverse events (AEs) occurring in study were reviewed for terms associated with hypersensitivity or anaphylaxis, and could also result in referral to the adjudication committee for evaluation.
Outcome measures
| Measure |
Placebo
n=76 Participants
Administration of 3 single IV doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
n=151 Participants
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
n=148 Participants
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
|---|---|---|---|
|
Percentage of Participants With Adjudicated Symptoms of Hypersensitivity
|
1.3 percentage of participants
Interval 0.0 to 7.1
|
6.6 percentage of participants
Interval 3.2 to 11.8
|
9.5 percentage of participants
Interval 5.3 to 15.4
|
SECONDARY outcome
Timeframe: Up to approximately 28 days after last dose (approximately 14 weeks)Population: APaT - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
The investigator or designated clinician performed a THA in each participant at 0.5, 4 and 24 hours after each dose. The THA could also be performed at other times if possible hypersensitivity signs were observed. Each potential hypersensitivity case identified by presence of any sign or symptom in a pre-defined list of hypersensitivity signs and symptoms that were found through the THA was reviewed by an independent, blinded adjudication committee, which determined whether the referred case was a case of anaphylaxis (yes/no) using Sampson Criterion 1 - Acute onset of an illness with involvement of the skin, mucosal tissue or both, and at least one of the following: a) respiratory compromise, b) reduced blood pressure or associated symptoms of end-organ dysfunction (J Allergy Clin Immunol 2006;117:391-397). All AEs occurring in study were reviewed for terms associated with hypersensitivity or anaphylaxis, and could also result in referral to the adjudication committee for evaluation.
Outcome measures
| Measure |
Placebo
n=76 Participants
Administration of 3 single IV doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
n=151 Participants
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
n=148 Participants
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
|---|---|---|---|
|
Percentage of Participants With Adjudicated Anaphylaxis
|
0.0 percentage of participants
Interval 0.0 to 4.7
|
0.0 percentage of participants
Interval 0.0 to 2.4
|
0.7 percentage of participants
Interval 0.0 to 3.7
|
Adverse Events
Placebo
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Sugammadex 4 mg/kg
Serious events: 2 serious events
Other events: 50 other events
Deaths: 0 deaths
Sugammadex 16 mg/kg
Serious events: 1 serious events
Other events: 75 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=76 participants at risk
Administration of 3 single IV doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
n=151 participants at risk
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
n=148 participants at risk
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
|---|---|---|---|
|
General disorders
Feeling hot
|
0.00%
0/76 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/151 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.68%
1/148 • Number of events 3 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Infections and infestations
Appendicitis
|
1.3%
1/76 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.66%
1/151 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/148 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Injury, poisoning and procedural complications
Brain contusion
|
1.3%
1/76 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/151 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/148 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/76 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.66%
1/151 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/148 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/76 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/151 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.68%
1/148 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Nervous system disorders
Headache
|
0.00%
0/76 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.00%
0/151 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
0.68%
1/148 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
Other adverse events
| Measure |
Placebo
n=76 participants at risk
Administration of 3 single IV doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 4 mg/kg
n=151 participants at risk
Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
Sugammadex 16 mg/kg
n=148 participants at risk
Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.3%
4/76 • Number of events 4 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
10.6%
16/151 • Number of events 21 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
13.5%
20/148 • Number of events 30 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Nervous system disorders
Dysgeusia
|
3.9%
3/76 • Number of events 3 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
7.3%
11/151 • Number of events 15 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
31.8%
47/148 • Number of events 80 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Nervous system disorders
Headache
|
13.2%
10/76 • Number of events 19 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
19.2%
29/151 • Number of events 45 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
20.3%
30/148 • Number of events 52 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.3%
4/76 • Number of events 4 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
1.3%
2/151 • Number of events 2 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
2.0%
3/148 • Number of events 3 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.3%
1/76 • Number of events 1 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
7.3%
11/151 • Number of events 16 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
5.4%
8/148 • Number of events 19 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/76 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
4.0%
6/151 • Number of events 11 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
6.8%
10/148 • Number of events 20 • Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER