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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004640-37 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sugammadex | Drug | Sugammadex 4 mg/kg or 16 mg/kg administered as a single IV bolus over 10 seconds |
|
| 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) |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30236237 | Result | 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. |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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One participant who was randomized to sugammadex 16 mg/kg instead received 3 doses of placebo and completed study. This participant appears in sugammadex 16 mg/kg column in Participant Flow period "Randomization through Start Treatment" and in placebo column in period "Treatment through Study Completion."
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Administration of 3 single intravenous (IV) doses of placebo, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3 |
| FG001 | 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 |
| FG002 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomization Through Start Treatment |
|
| ||||||||||||||||||
| Treatment Through Study Completion |
|
All participants as treated (APaT) - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Sugammadex 4 mg/kg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | APaT - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to approximately 28 days after last dose (approximately 14 weeks) |
Up to approximately 28 days after last dose (approximately 14 weeks)
Analysis performed using APaT population - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Feeling hot | General disorders | MedDRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006967 | Hypersensitivity |
| D000707 | Anaphylaxis |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D006969 | Hypersensitivity, Immediate |
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| ID | Term |
|---|---|
| D000077122 | Sugammadex |
| ID | Term |
|---|---|
| D047408 | gamma-Cyclodextrins |
| D003505 | Cyclodextrins |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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| Placebo | Drug | Placebo administered as a single IV bolus over 10 seconds |
|
| Up to approximately 28 days after last dose (approximately 14 weeks) |
|
| Received Second Dose |
|
| Received Third Dose |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
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
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
|
|
| Secondary | 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. | APaT - All randomized participants who received at least one dose of study treatment, with each participant included in arm corresponding to treatment actually received. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to approximately 28 days after last dose (approximately 14 weeks) |
|
|
|
|
| 2 |
| 76 |
| 18 |
| 76 |
| EG001 | 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 | 2 | 151 | 50 | 151 |
| EG002 | 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 | 1 | 148 | 75 | 148 |
| Appendicitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
|
| Brain contusion | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
| D003912 |
| Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| Difference in incidence |
| 0.7 |
| 2-Sided |
| 95 |
| -4.2 |
| 3.7 |
Difference is Sugammadex 16 mg/kg incidence minus Placebo incidence. Confidence interval calculated using method of Miettinen and Nurminen (Statistics in Medicine 1985;4:213-226). |
| Superiority or Other |