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| ID | Type | Description | Link |
|---|---|---|---|
| EUDRACT: 2009-012014-40 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sugammadex 4 mg/kg | Experimental | Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
|
| Sugammadex 16 mg/kg | Experimental | Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
|
| Placebo | Placebo Comparator | Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo run-in dose | Drug | Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo. | Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists & allergists/immunologists) for blinded review and determination of adjudicated hypersensitivity &/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity at any dose (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) were compared between the 3 treatment groups. | Day 8, Day 36, and Day 78 of the study |
| Measure | Description | Time Frame |
|---|---|---|
| The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo. | The Adjudication Committee evaluated each case to determine whether the subject's hypersensitivity sign/symptoms fulfilled the definition of anaphylaxis according to the criteria defined by the Symposium on the Definition and Management of Anaphylaxis as described by Sampson et al. (J Allergy Clin Immunol 2006; 117:391-7). The percentages of subjects who had adjudicated anaphylaxis according to the Sampson Criteria at any dose (dose 1 [~Day 8], dose 2 [~Day 36], or dose 3 [Day ~78]) were compared between the 3 treatment groups. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | All adverse events from the study were reviewed for potential safety signals. The reported incidences suggestive of a dose-dependent trend and with a frequency threshold above 5% (including both serious and non-serious adverse events) are presented. |
Inclusion Criteria:
Exclusion Criteria:
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30236238 | Background | 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. |
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A total of 480 participants received a single-blind placebo dose 7 days prior to randomization. Of these 480 participants, 448 were randomized to double-blind treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sugammadex 4 mg/kg | Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| FG001 | Sugammadex 16 mg/kg | Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| FG002 | Placebo | Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sugammadex 4 mg/kg | Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| BG001 | Sugammadex 16 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 | The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms, for Each Sugammadex Dose Group and Placebo. | Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists & allergists/immunologists) for blinded review and determination of adjudicated hypersensitivity &/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity at any dose (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) were compared between the 3 treatment groups. | All-Subjects as treated (i.e., who received at least one dose of randomized study medication). | Posted | Number | 95% Confidence Interval | percentage of participants | Day 8, Day 36, and Day 78 of the study |
|
Adverse Events (AEs) that started after first dose of randomized study medication up to 30 days after day of last dose of randomized study medication, i.e. the "Treatment-emergent" AEs.
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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 | Sugammadex 4 mg/kg | Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA (13.0) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (13.0) |
Results from this study in healthy/conscious subjects may not be fully applicable to anesthetized patient settings.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006967 | Hypersensitivity |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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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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| Sugammadex 4 mg/kg | Drug | Sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study |
|
|
| Sugammadex 16 mg/kg | Drug | Sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study |
|
|
| Placebo | Drug | Placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study |
|
| Day 8, Day 36, and Day 78 of the study |
| 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. | The Adjudication Committee evaluated each case to determine anaphylaxis according to the criteria put forth by the guidelines of the Brighton Collaboration Anaphylaxis Working Group as described by Rüggeberg et al. (Vaccine 2007; 25:5675-5684). Level 1 represents the highest level of certainty of anaphylaxis and level 3 the lowest level of certainty. The percentages of subjects who had adjudicated anaphylaxis according to the Rüggeberg Criteria at any dose (dose 1 [~Day 8], dose 2 [~Day 36], or dose 3 [Day ~78]) were compared between the 3 treatment groups. | Day 8, Day 36, and Day 78 of the study |
| The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo. | Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists & allergists/immunologists) for blinded review & determination of adjudicated hypersensitivity &/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) are presented for each of the 3 treatment arms for each dose. | Day 8, Day 36, and Day 78 of the study |
| From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication. |
| Subject withdrew consent |
|
| Noncompliance with protocol |
|
Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study.
| BG002 | Placebo | Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants were to receive one dose of sugammadex 4 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| OG001 | Sugammadex 16 mg/kg | Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
| OG002 | Placebo | Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. |
|
|
|
| Secondary | The Percentage of Participants With Adjudicated Anaphylaxis According to the Definition by Sampson et al., for Each Sugammadex Dose Group and Placebo. | The Adjudication Committee evaluated each case to determine whether the subject's hypersensitivity sign/symptoms fulfilled the definition of anaphylaxis according to the criteria defined by the Symposium on the Definition and Management of Anaphylaxis as described by Sampson et al. (J Allergy Clin Immunol 2006; 117:391-7). The percentages of subjects who had adjudicated anaphylaxis according to the Sampson Criteria at any dose (dose 1 [~Day 8], dose 2 [~Day 36], or dose 3 [Day ~78]) were compared between the 3 treatment groups. | All-Subjects as treated (i.e., who received at least one dose of randomized study medication). | Posted | Number | 95% Confidence Interval | percentage of participants | Day 8, Day 36, and Day 78 of the study |
|
|
|
|
| Secondary | 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. | The Adjudication Committee evaluated each case to determine anaphylaxis according to the criteria put forth by the guidelines of the Brighton Collaboration Anaphylaxis Working Group as described by Rüggeberg et al. (Vaccine 2007; 25:5675-5684). Level 1 represents the highest level of certainty of anaphylaxis and level 3 the lowest level of certainty. The percentages of subjects who had adjudicated anaphylaxis according to the Rüggeberg Criteria at any dose (dose 1 [~Day 8], dose 2 [~Day 36], or dose 3 [Day ~78]) were compared between the 3 treatment groups. | All-Subjects as treated (i.e., who received at least one dose of randomized study medication). | Posted | Number | percentage of participants | Day 8, Day 36, and Day 78 of the study |
|
|
|
|
| Secondary | The Percentage of Participants With Adjudicated Hypersensitivity Signs/Symptoms After Each Randomized Dose of Study Treatment, for Each Sugammadex Dose Group and Placebo. | Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists & allergists/immunologists) for blinded review & determination of adjudicated hypersensitivity &/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) are presented for each of the 3 treatment arms for each dose. | All-Subjects as treated, per dose (i.e. who received the corresponding dose of randomized study medication). | Posted | Number | percentage of participants | Day 8, Day 36, and Day 78 of the study |
|
|
|
| Other Pre-specified | 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). | All adverse events from the study were reviewed for potential safety signals. The reported incidences suggestive of a dose-dependent trend and with a frequency threshold above 5% (including both serious and non-serious adverse events) are presented. | All-Subjects as treated (i.e., who received at least one dose of randomized study medication). | Posted | Number | percentage of participants | From first randomized dose (Day 8) up to 30 days after day of last randomized dose of study medication. |
|
|
|
| 0 |
| 148 |
| 35 |
| 148 |
| EG001 | Sugammadex 16 mg/kg | Participants were to receive one dose of sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. | 2 | 150 | 64 | 150 |
| EG002 | Placebo | Participants were to receive one dose of placebo intravenous bolus injection on Day 8, Day 36, and Day 78 of the study. | 1 | 150 | 33 | 150 |
| Anaphylactic shock | Immune system disorders | MedDRA (13.0) |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (13.0) |
|
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (13.0) |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (13.0) |
|
| Flushing | Vascular disorders | MedDRA (13.0) |
|
| Hypotension | Vascular disorders | MedDRA (13.0) |
|
| Nasopharyngitis | Infections and infestations | MedDRA (13.0) |
|
| Dysgeusia | Nervous system disorders | MedDRA (13.0) |
|
| Headache | Nervous system disorders | MedDRA (13.0) |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) |
|
Investigator may not publish/publicly present interim results without prior consent of Sponsor. Any materials that report results of the study must be sent to Sponsor 45 days prior to submission for publication/presentation. Sponsor has right to review and comment. In case of any disagreements concerning appropriateness of the materials, investigator and Sponsor must meet to make a good faith effort to discuss/resolve the issues or disagreement, prior to submission for publication/presentation.
| D003912 |
| Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| Difference in event rates |
| 0 |
| 95 |
| -2.5 |
| 2.5 |
95% confidence interval for the difference in event rates (treatment group minus placebo) according to Miettinen and Nurminen (Statistics in Medicine 1985; 4:213-226). |
| Superiority or Other |
| Title | Measurements |
|---|---|
|
| Level 3 |
|
| Level 1 or Level 2 |
|
Comparison of participants who had Level 1 or Level 2 diagnostic certainty. |
| Difference in event rates |
| 0 |
| 95 |
| -2.5 |
| 2.5 |
95% confidence interval for the difference in event rates (treatment group minus placebo) according to Miettinen and Nurminen (Statistics in Medicine 1985; 4:213-226). |
| Superiority or Other |
|
| 3rd randomized dose (n=135; n=127; n=135) |
|
| after any randomized dose |
|
| Title | Measurements |
|---|---|
|
| Dysgeusia |
|