Clinical trial NCT00988065: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypersensitivity
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-10-01
Enrollment: 448
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo.
timeFrame: Day 8, Day 36, and Day 78 of the study
Secondary outcomes:
measure: The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo.
timeFrame: Day 8, Day 36, and Day 78 of the study
measure: 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.
timeFrame: Day 8, Day 36, and Day 78 of the study
measure: The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo.
timeFrame: Day 8, Day 36, and Day 78 of the study
Other outcomes:
measure: 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).
timeFrame: From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication.
Locations:
Study officials:
References:
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.