A Study to Evaluate the Incidence of Hypersensitivity After Administration of Sugammadex in Healthy Participants (MK-8616-101)

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Incidence of Hypersensitivity After Repeated Single Dose Administration of Sugammadex (MK-8616) in Healthy Subjects

The purpose of this study is to assess the potential for hypersensitivity symptoms upon repeat exposure to sugammadex. Healthy participants will be randomized to one of three treatment arms: sugammadex 4 mg/kg, sugammadex 16 mg/kg or placebo. Participants will receive 3 single intravenous (IV) doses of their randomized treatment, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3. Participants will be confined at the study center from the day before each dose until completion of the 24-hour post dose assessments.

Study Overview

• Status: Completed
• Conditions: Hypersensitivity; Anaphylaxis
• Intervention / Treatment: Drug: Sugammadex; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 382
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant and non-breast feeding female
• Females of childbearing potential must have a serum β-human chorionic gonadotropin (β-hCG) level consistent with non-pregnant state and agree to use (and/or have their partner use) two acceptable methods of birth control beginning at screening, throughout the trial (including washout intervals between treatment periods) and until after the post-study follow-up visit
• Females not of childbearing potential must be either a) postmenopausal (have not had a menstrual period for at least 1 year and have a follicle stimulating hormone [FSH] value in the postmenopausal range) or b) surgically sterile (i.e., have had hysterectomy, oophorectomy or tubal ligation)
• In good health based on medical history, laboratory tests and other assessments
• Body Mass Index (BMI) ≥19 and ≤32 kg/m^2
• Non-smoker or smokes ≤10 cigarettes/day or equivalent (2 pipes/day, 1 cigar/day) and agrees not to smoke while confined at the study center

Exclusion Criteria:

• Mentally or legally incapacitated, has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
• History of cancer (malignancy)
• History of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
• Has had major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
• Has participated in another investigational trial within 4 weeks prior to screening
• Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial (including washout intervals between treatment periods), until the post-study follow-up visit
• Has received subcutaneous or sublingual immunotherapy within the past 1 year
• Consumes >3 glasses of alcoholic beverages per day
• Consumes excessive amounts, defined as >6 servings of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
• Currently a regular user (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months
• Has a recollection of previously receiving sugammadex, Bridion™, SCH 900616, ORG 25969, or MK-8616
• History of chronic urticaria or angioedema
• Is or has an immediate family member (spouse or children) who is a member of investigational site or sponsor staff directly involved with this trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex 4 mg/kg; Administration of 3 single IV doses of sugammadex 4 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3	Drug: Sugammadex; Sugammadex 4 mg/kg or 16 mg/kg administered as a single IV bolus over 10 seconds
Experimental: Sugammadex 16 mg/kg; Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3	Drug: Sugammadex; Sugammadex 4 mg/kg or 16 mg/kg administered as a single IV bolus over 10 seconds
Placebo Comparator: Placebo; Administration of 3 single IV doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3	Drug: Placebo; Placebo administered as a single IV bolus over 10 seconds

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adjudicated Symptoms of Hypersensitivity	The investigator or designated clinician performed a targeted hypersensitivity assessment (THA) in each participant at 0.5, 4 and 24 hours after each dose for each dosing period. The THA could also be performed at other times if possible hypersensitivity signs were observed. The THA included elicitation of symptoms as well as examination of the participant, covering neurologic, pulmonary, cardiovascular, gastrointestinal and dermatologic domains. Each potential hypersensitivity case identified by the presence of any sign or symptom in a pre-defined list of hypersensitivity signs and symptoms that were found through the THA was reviewed by an independent, blinded adjudication committee, which determined whether the referred case was a case of hypersensitivity (yes/no). In addition, all adverse events (AEs) occurring in study were reviewed for terms associated with hypersensitivity or anaphylaxis, and could also result in referral to the adjudication committee for evaluation.	Up to approximately 28 days after last dose (approximately 14 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adjudicated Anaphylaxis	The investigator or designated clinician performed a THA in each participant at 0.5, 4 and 24 hours after each dose. The THA could also be performed at other times if possible hypersensitivity signs were observed. Each potential hypersensitivity case identified by presence of any sign or symptom in a pre-defined list of hypersensitivity signs and symptoms that were found through the THA was reviewed by an independent, blinded adjudication committee, which determined whether the referred case was a case of anaphylaxis (yes/no) using Sampson Criterion 1 - Acute onset of an illness with involvement of the skin, mucosal tissue or both, and at least one of the following: a) respiratory compromise, b) reduced blood pressure or associated symptoms of end-organ dysfunction (J Allergy Clin Immunol 2006;117:391-397). All AEs occurring in study were reviewed for terms associated with hypersensitivity or anaphylaxis, and could also result in referral to the adjudication committee for evaluation.	Up to approximately 28 days after last dose (approximately 14 weeks)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Min KC, Bondiskey P, Schulz V, Woo T, Assaid C, Yu W, Reynders T, Declercq R, McCrea J, Dennie J, Adkinson F, Shepherd G, Gutstein DE. Hypersensitivity incidence after sugammadex administration in healthy subjects: a randomised controlled trial. Br J Anaesth. 2018 Oct;121(4):749-757. doi: 10.1016/j.bja.2018.05.056. Epub 2018 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 3, 2014
• First Submitted That Met QC Criteria: January 3, 2014
• First Posted (Estimate): January 6, 2014

Study Record Updates

• Last Update Posted (Actual): April 3, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: reversal of neuromuscular blockade
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Anaphylaxis
• Other Study ID Numbers: 8616-101; 2013-004640-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis