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Sugammadex Hypersensitivity Study (Study P06042)

Primary Purpose

Hypersensitivity

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Placebo run-in dose
Sugammadex 4 mg/kg
Sugammadex 16 mg/kg
Placebo
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypersensitivity

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Sugammadex 4 mg/kg

    Sugammadex 16 mg/kg

    Placebo

    Arm Description

    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.

    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.

    Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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.

    Full Information

    First Posted
    September 30, 2009
    Last Updated
    January 11, 2019
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00988065
    Brief Title
    Sugammadex Hypersensitivity Study (Study P06042)
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    September 6, 2009 (Actual)
    Primary Completion Date
    April 13, 2010 (Actual)
    Study Completion Date
    April 13, 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hypersensitivity

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    448 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Sugammadex 4 mg/kg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Sugammadex 16 mg/kg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo run-in dose
    Intervention Description
    Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization
    Intervention Type
    Drug
    Intervention Name(s)
    Sugammadex 4 mg/kg
    Other Intervention Name(s)
    SCH 900616, Org 25969, Bridion®
    Intervention Description
    Sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study
    Intervention Type
    Drug
    Intervention Name(s)
    Sugammadex 16 mg/kg
    Other Intervention Name(s)
    SCH 900616, Org 25969, Bridion®
    Intervention Description
    Sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study
    Primary Outcome Measure Information:
    Title
    The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo.
    Description
    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.
    Time Frame
    Day 8, Day 36, and Day 78 of the study
    Secondary Outcome Measure Information:
    Title
    The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo.
    Description
    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.
    Time Frame
    Day 8, Day 36, and Day 78 of the study
    Title
    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.
    Description
    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.
    Time Frame
    Day 8, Day 36, and Day 78 of the study
    Title
    The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo.
    Description
    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.
    Time Frame
    Day 8, Day 36, and Day 78 of the study
    Other Pre-specified Outcome Measures:
    Title
    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).
    Description
    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.
    Time Frame
    From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    30236238
    Citation
    de Kam PJ, Nolte H, Good S, Yunan M, Williams-Herman DE, Burggraaf J, Kluft C, Adkinson NF, Cullen C, Skov PS, Levy JH, van den Dobbelsteen DJ, van Heumen ELGM, van Meel FCM, Glassner D, Woo T, Min KC, Peeters PAM. Sugammadex hypersensitivity and underlying mechanisms: a randomised study of healthy non-anaesthetised volunteers. Br J Anaesth. 2018 Oct;121(4):758-767. doi: 10.1016/j.bja.2018.05.057. Epub 2018 Jul 13.
    Results Reference
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    Sugammadex Hypersensitivity Study (Study P06042)

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