Sugammadex Hypersensitivity Study (Study P06042)

January 11, 2019 updated by: Merck Sharp & Dohme LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

448

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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

What is the study measuring?

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.
Time Frame: Day 8, Day 36, and Day 78 of the study

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.
Time Frame: Day 8, Day 36, and Day 78 of the study

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.
Time Frame: Day 8, Day 36, and Day 78 of the study

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.
Time Frame: Day 8, Day 36, and Day 78 of the study

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 6, 2009

Primary Completion (Actual)

April 13, 2010

Study Completion (Actual)

April 13, 2010

Study Registration Dates

First Submitted

September 30, 2009

First Submitted That Met QC Criteria

September 30, 2009

First Posted (Estimate)

October 1, 2009

Study Record Updates

Last Update Posted (Actual)

January 30, 2019

Last Update Submitted That Met QC Criteria

January 11, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P06042
  • EUDRACT: 2009-012014-40

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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