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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Sugammadex

Placebo

About this trial

This is an interventional treatment trial for Hypersensitivity focused on measuring reversal of neuromuscular blockade

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Sugammadex 4 mg/kg

Sugammadex 16 mg/kg

Placebo

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02028065

First Posted

January 3, 2014

Last Updated

March 25, 2019

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02028065

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

January 3, 2014 (Actual)

Primary Completion Date

July 1, 2014 (Actual)

Study Completion Date

July 1, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypersensitivity, Anaphylaxis

Keywords

reversal of neuromuscular blockade

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

382 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sugammadex 4 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sugammadex 16 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sugammadex

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo administered as a single IV bolus over 10 seconds

Primary Outcome Measure Information:

Title

Percentage of Participants With Adjudicated Symptoms of Hypersensitivity

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

Percentage of Participants With Adjudicated Anaphylaxis

Description

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.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

30236237

Citation

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.

Results Reference

result

Available IPD and Supporting Information:

Available IPD/Information Type

CSR Synopsis

Available IPD/Information URL

http://www.merck.com/clinical-trials/study.html?id=8616-101&kw=8616-101&tab=access

Hypersensitivity, Anaphylaxis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial