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

NCT02028065 | Completed Phase 1 Results

• 2 other identifiers: 8616-1012013-004640-37
• Study Type: interventional
• Target: 382
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hypersensitivity; Anaphylaxis

Keywords

reversal of neuromuscular blockade

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percentage of Participants With Adjudicated Anaphylaxis

  Up to approximately 28 days after last dose (approximately 14 weeks)

Study Arms (3)

Sugammadex 4 mg/kg

EXPERIMENTAL

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 16 mg/kg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Sugammadex DRUG

Sugammadex 4 mg/kg or 16 mg/kg administered as a single IV bolus over 10 seconds

Sugammadex 16 mg/kg; Sugammadex 4 mg/kg

Placebo DRUG

Placebo administered as a single IV bolus over 10 seconds

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 30236237 RESULT

MeSH Terms

Conditions

Hypersensitivity; Anaphylaxis

Interventions

Sugammadex

Condition Hierarchy (Ancestors)

Immune System Diseases; Hypersensitivity, Immediate

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 3, 2014
• First Posted: January 6, 2014
• Study Start: January 3, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 3, 2019
• Results First Posted: October 2, 2015

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share