Sugammadex Hypersensitivity Study (Study P06042)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00988065
First received: September 30, 2009
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Hypersensitivity
Drug: Placebo run-in dose
Drug: Sugammadex 4 mg/kg
Drug: Sugammadex 16 mg/kg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo. [ Time Frame: Day 8, Day 36, and Day 78 of the study ] [ Designated as safety issue: Yes ]

    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. [ Time Frame: Day 8, Day 36, and Day 78 of the study ] [ Designated as safety issue: Yes ]

    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. [ Time Frame: Day 8, Day 36, and Day 78 of the study ] [ Designated as safety issue: Yes ]

    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. [ Time Frame: Day 8, Day 36, and Day 78 of the study ] [ Designated as safety issue: Yes ]

    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.



Other Outcome Measures:
  • 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). [ Time Frame: From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 448
Study Start Date: September 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Placebo run-in dose
Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization
Drug: Sugammadex 4 mg/kg
Sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study
Other Name: SCH 900616, Org 25969, Bridion®
Experimental: 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.
Drug: Placebo run-in dose
Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization
Drug: Sugammadex 16 mg/kg
Sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study
Other Name: SCH 900616, Org 25969, Bridion®
Placebo Comparator: Placebo
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
Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization
Drug: Placebo
Placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00988065     History of Changes
Other Study ID Numbers: P06042, EUDRACT: 2009-012014-40
Study First Received: September 30, 2009
Results First Received: April 13, 2011
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014