Sugammadex Hypersensitivity Study (Study P06042)

NCT00988065 | Completed Phase 1 Results DMC

• 2 other identifiers: P06042EUDRACT: 2009-012014-40
• Study Type: interventional
• Target: 448
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypersensitivity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo.

  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.

  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.

  Day 8, Day 36, and Day 78 of the study

Other Outcomes (1)

• 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).

  From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication.

Study Arms (3)

Sugammadex 4 mg/kg

EXPERIMENTAL

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; Drug: Sugammadex 4 mg/kg

Sugammadex 16 mg/kg

EXPERIMENTAL

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; Drug: Sugammadex 16 mg/kg

Placebo

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Placebo run-in dose DRUG

Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization

Placebo; Sugammadex 16 mg/kg; Sugammadex 4 mg/kg

Sugammadex 4 mg/kg DRUG

Sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study

Also known as: SCH 900616, Org 25969, Bridion®

Sugammadex 4 mg/kg

Sugammadex 16 mg/kg DRUG

Sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study

Also known as: SCH 900616, Org 25969, Bridion®

Sugammadex 16 mg/kg

Placebo DRUG

Placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 30236238 BACKGROUND

MeSH Terms

Conditions

Hypersensitivity

Interventions

Sugammadex

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates

Limitations and Caveats

Results from this study in healthy/conscious subjects may not be fully applicable to anesthetized patient settings.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2009
• First Posted: October 1, 2009
• Study Start: September 6, 2009
• Primary Completion: April 13, 2010
• Study Completion: April 13, 2010
• Last Updated: January 30, 2019
• Results First Posted: July 11, 2011

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share