Sugammadex Hypersensitivity Study (Study P06042)

Study Overview
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Brief Summary
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This trial was conducted to study the potential for hypersensitivity symptoms at the time of initial exposure to sugammadex and upon repeat exposure, since it was unknown whether the frequency or severity of hypersensitivity symptoms may worsen at repeat exposure over a prolonged period. In total 450 participants (all healthy subjects) were to be randomized to receive one of three study treatments: three repeated doses of either sugammadex 4 mg/kg, sugammadex 16 mg/kg, or placebo. Participants were to receive one dose of study treatment on Day 8, Day 36, and Day 78 of the study in order to determine the safety of each treatment dose.

Detailed Description
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All subjects were to be admitted to the study center the day before each scheduled dose and were to leave the unit the morning of the day after each dose. In cases of suspected hypersensitivity symptoms, healthy subjects were to remain confined to the study center until all signs and symptoms regressed, the subject was stable, and the investigator considered it safe for the subject to leave the study center. Four sites participated in this trial.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Incidence of Hypersensitivity After Repeated Single Dose Administrations of Sugammadex (SCH 900616) in Healthy Subjects

Conditions
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Hypersensitivity

Intervention / Treatment
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* Drug: Placebo run-in dose
* Drug: Sugammadex 4 mg/kg
* Drug: Sugammadex 16 mg/kg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-55 years of age Serum tryptase <=11.4 mcg/L and fasting triglyceride levels within normal limits Safety laboratory tests and vital signs must have been within normal limits Screening electrocardiogram must have been clinically acceptable and parameters within normal limits Body Mass Index between 19 and 32 kg/m^2 Females must have agreed to use contraceptives Other certain administrative criteria as described in the protocol Exclusion Criteria: Females who were pregnant or intending to become pregnant Subjects who would not be able to participate optimally in the study, in the opinion of the investigator Certain surgical or medical conditions, recent infections, or mental instability Positive test for certain drugs or history of alcohol or drug abuse Positive test for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV) Blood donation in the past 60 days A history of unexplained reaction or hypersensitivity reaction during previous surgery and/or anesthesia History of anaphylaxis from any cause, suspected history of hypersensitivity to cyclodextrins, or multiple drug hypersensitivities Heavy smoker Received certain medications in the past History of allergy, hypersensitivity, or intolerance to epinephrine at greater risk of developing adverse reactions after epinephrine administration Other certain administrative criteria as described in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex 4 mg/kg<br>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. | Drug: Placebo run-in dose<br>* Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization<br>Drug: Sugammadex 4 mg/kg<br>* Sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study<br>* Other names: SCH 900616, Org 25969, Bridion®;|
| Experimental: Sugammadex 16 mg/kg<br>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. | Drug: Placebo run-in dose<br>* Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization<br>Drug: Sugammadex 16 mg/kg<br>* Sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study<br>* Other names: SCH 900616, Org 25969, Bridion®;|
| Placebo Comparator: Placebo<br>Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. | Drug: Placebo run-in dose<br>* Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization<br>Drug: Placebo<br>* Placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo. | 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. | Day 8, Day 36, and Day 78 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo. | 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. | 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. | 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. | 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. | 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. | Day 8, Day 36, and Day 78 of the study |