Neuromuscular Blockade
Conditions
Brief summary
This trial will evaluate the efficacy, safety, and pharmacokinetics of sugammadex for the reversal of both moderate and deep neuromuscular blockade (NMB) induced by either rocuronium or vecuronium in pediatric participants. The primary efficacy hypothesis of this investigation is that sugammadex is superior to neostigmine in reversing moderate NMB in pediatric participants as measured by time to recovery to a train-of-four (TOF) ratio of ≥0.9.
Detailed description
This trial will be conducted in two parts: Part A and Part B. In Part A, pharmacokinetic (PK) sampling will be conducted to identify the pediatric dose providing sugammadex exposure similar to adults. For Part B participants, the efficacy of sugammadex (i.e. time to recovery of the TOF ratio) will be assessed. Further, safety analyses will be conducted in both Parts A and B. Following completion of Part A, an interim analysis (IA) of the PK and safety data will be performed. Once the appropriate doses are confirmed and safety data is assessed for the 2 doses of sugammadex, then Part B will commence.
Interventions
For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) will be given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).
For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as glycopyrrolate (10 μg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as atropine (20 μg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Be categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1, 2, or 3. * Have a planned non-emergent surgical procedure or clinical situation (e.g., intubation) that requires moderate or deep NMB with either rocuronium or vecuronium. * Have a planned surgical procedure or clinical situation that would allow objective neuromuscular monitoring techniques to be applied with access to the arm for neuromuscular transmission monitoring. * Age between 2 to \<17 years at Visit 2. * If female, may participate if she is not pregnant, not breastfeeding, and at least one of the following: 1) Not a woman of childbearing potential (WOCBP); or 2) A WOCBP who agrees to follow the study contraceptive guidance during the treatment period and for at least 7 days after the last dose of study treatment.
Exclusion criteria
* Has any clinically significant condition or situation (eg, anatomical malformation that complicates intubation) other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial. * Has a neuromuscular disorder that may affect NMB and/or trial assessments. * Is dialysis-dependent or has (or is suspected of having) severe renal insufficiency (defined as estimated glomerular filtration rate (eGFR) \<30 ml/min). * Has or is suspected of having a family or personal history of malignant hyperthermia. * Has or is suspected of having an allergy to study treatments or its/their excipients, to opioids/opiates, muscle relaxants or their excipients, or other medication(s) used during general anesthesia. * Has received or is planned to receive toremifene and/or fusidic acid via IV administration within 24 hours before or within 24 hours after administration of study treatment. * Has been previously treated with sugammadex or has participated in a sugammadex clinical trial. * Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing the informed consent/assent for this current trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B] | Up to 30 minutes post-dose | The time to recovery of TOF ratio to ≥0.9 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. Per protocol, the efficacy analysis is based on comparison of the Part B: Sugammadex 2 mg arm versus the Part B: Neostigmine + (Glycopyrrolate or Atropine) arm. |
| Plasma Half-Life (t½) of Sugammadex [Part A] | 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose | The t½ of sugammadex, defined as the time required for the plasma concentration to decrease to 50% of maximum, was determined in each Part A arm. |
| Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B] | Up to 7 days | The percentage of participants with ≥1 AE(s) for up to 7 days after treatment was determined for each treatment group, pooled according to treatment received. An AE is defined as any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. |
| Plasma Clearance (CL) of Sugammadex [Part A] | 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose | The CL of sugammadex, defined as the rate of elimination relative to plasma concentration, was determined in each Part A arm. |
| Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose | The AUCo-∞ for sugammadex, defined as the area under the plasma concentration versus time plot, was determined in each Part A arm. |
| Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose | The Vz of sugammadex, defined as the amount of drug administered relative to plasma concentrations, was determined in each Part A arm. |
| Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose | The Cmax of sugammadex, defined as the maximum plasma concentration, was determined in each Part A arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B] | Up to 30 minutes post-dose | The time to recovery of TOF ratio to ≥0.8 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. |
| Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B] | Up to 30 minutes post-dose | The time to recovery of TOF ratio to ≥0.7 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. |
Countries
Austria, Belgium, Denmark, Finland, Germany, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
Male and female participants 2 to \<17 years of age who are categorized as American Society of Anesthesiologists (ASA) Physical Class 1, 2, or 3 and had a planned medical and/or surgical procedure requiring moderate or deep neuromuscular blockade (NMB) with rocuronium (ROC) or vecuronium (VEC) that would allow for neuromuscular monitoring were recruited.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Sugammadex 2 mg/kg For moderate NMB reversal, a single intravenous (i.v.) bolus of sugammadex (2 mg/kg) is given after the final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations. | 19 |
| Part A: Sugammadex 4 mg For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) is given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0). | 23 |
| Part B: Sugammadex 2 mg/kg For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) is given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations. | 35 |
| Part B: Sugammadex 4 mg/kg For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) is given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0). | 176 |
| Part B: Neostigmine + (Glycopyrrolate or Atropine) For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as either glycopyrrolate (10 μg/kg) or atropine (20 µg/kg) is given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations. | 35 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 | 1 |
| Overall Study | Other | 0 | 1 | 1 | 3 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 2 | 1 |
| Overall Study | Randomized by mistake, no treatment given | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by parent/guardian | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A: Sugammadex 2 mg/kg | Part A: Sugammadex 4 mg | Part B: Sugammadex 2 mg/kg | Part B: Sugammadex 4 mg/kg | Part B: Neostigmine + (Glycopyrrolate or Atropine) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 7.1 years STANDARD_DEVIATION 4.7 | 7.2 years STANDARD_DEVIATION 5 | 7.9 years STANDARD_DEVIATION 4.4 | 7.9 years STANDARD_DEVIATION 4.4 | 8.7 years STANDARD_DEVIATION 4.4 | 7.9 years STANDARD_DEVIATION 4.4 |
| Age, Customized Adolescents (12-17 years) | 4 Participants | 6 Participants | 10 Participants | 44 Participants | 10 Participants | 74 Participants |
| Age, Customized Children (2-11 years) | 15 Participants | 17 Participants | 25 Participants | 132 Participants | 25 Participants | 214 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 16 Participants | 17 Participants | 30 Participants | 161 Participants | 33 Participants | 257 Participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 20 Participants | 95 Participants | 18 Participants | 156 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 15 Participants | 81 Participants | 17 Participants | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 | 0 / 4 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 33 | 0 / 169 | 0 / 34 |
| other Total, other adverse events | 8 / 9 | 3 / 5 | 2 / 4 | 8 / 10 | 5 / 6 | 6 / 6 | 26 / 33 | 117 / 169 | 29 / 34 |
| serious Total, serious adverse events | 0 / 9 | 0 / 5 | 0 / 4 | 0 / 10 | 0 / 6 | 0 / 6 | 3 / 33 | 3 / 169 | 2 / 34 |
Outcome results
Primary
Apparent Volume of Distribution (Vz) of Sugammadex [Part A]
The Vz of sugammadex, defined as the amount of drug administered relative to plasma concentrations, was determined in each Part A arm.
Time frame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
Population: All participants with ≥5 post-dosing samples available are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 3.58 Liters | Geometric Coefficient of Variation 21.3 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 6.65 Liters | Geometric Coefficient of Variation 33.5 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 10.8 Liters | Geometric Coefficient of Variation 34.8 |
| Part A: Sugammadex 4 mg (2 to <6 Years) | Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 4.00 Liters | Geometric Coefficient of Variation 37.7 |
| Part A: Sugammadex 4 mg (6 to <12 Years) | Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 8.22 Liters | Geometric Coefficient of Variation 82.9 |
| Part A: Sugammadex 4 mg (12 to <17 Years) | Apparent Volume of Distribution (Vz) of Sugammadex [Part A] | 12.3 Liters | Geometric Coefficient of Variation 35.9 |
Primary
Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A]
The AUCo-∞ for sugammadex, defined as the area under the plasma concentration versus time plot, was determined in each Part A arm.
Time frame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
Population: All participants with ≥5 post-dosing samples available are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 14.1 hr*μg/mL | Geometric Coefficient of Variation 19.4 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 18.8 hr*μg/mL | Geometric Coefficient of Variation 27.4 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 27.6 hr*μg/mL | Geometric Coefficient of Variation 58 |
| Part A: Sugammadex 4 mg (2 to <6 Years) | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 26.9 hr*μg/mL | Geometric Coefficient of Variation 18.5 |
| Part A: Sugammadex 4 mg (6 to <12 Years) | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 38.2 hr*μg/mL | Geometric Coefficient of Variation 73 |
| Part A: Sugammadex 4 mg (12 to <17 Years) | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] | 49.2 hr*μg/mL | Geometric Coefficient of Variation 20.1 |
Primary
Maximum Plasma Concentration (Cmax) of Sugammadex [Part A]
The Cmax of sugammadex, defined as the maximum plasma concentration, was determined in each Part A arm.
Time frame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
Population: All participants with ≥5 post-dosing samples available are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 17.5 µg/mL | Geometric Coefficient of Variation 33.1 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 32.2 µg/mL | Geometric Coefficient of Variation 15.6 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 41.3 µg/mL | Geometric Coefficient of Variation 85.8 |
| Part A: Sugammadex 4 mg (2 to <6 Years) | Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 47.1 µg/mL | Geometric Coefficient of Variation 22.1 |
| Part A: Sugammadex 4 mg (6 to <12 Years) | Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 51.6 µg/mL | Geometric Coefficient of Variation 69.2 |
| Part A: Sugammadex 4 mg (12 to <17 Years) | Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] | 61.9 µg/mL | Geometric Coefficient of Variation 13.5 |
Primary
Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B]
The percentage of participants with ≥1 AE(s) for up to 7 days after treatment was determined for each treatment group, pooled according to treatment received. An AE is defined as any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated.
Time frame: Up to 7 days
Population: Each participant who received a dose of study drug is included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B] | 97.1 Percentage of Participants |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B] | 78.4 Percentage of Participants |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B] | 74.9 Percentage of Participants |
Primary
Plasma Clearance (CL) of Sugammadex [Part A]
The CL of sugammadex, defined as the rate of elimination relative to plasma concentration, was determined in each Part A arm.
Time frame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
Population: All participants with ≥5 post-dosing samples available are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Plasma Clearance (CL) of Sugammadex [Part A] | 2.30 L/hr | Geometric Coefficient of Variation 21.4 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Plasma Clearance (CL) of Sugammadex [Part A] | 3.58 L/hr | Geometric Coefficient of Variation 26.2 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Plasma Clearance (CL) of Sugammadex [Part A] | 4.68 L/hr | Geometric Coefficient of Variation 52.5 |
| Part A: Sugammadex 4 mg (2 to <6 Years) | Plasma Clearance (CL) of Sugammadex [Part A] | 2.26 L/hr | Geometric Coefficient of Variation 29.4 |
| Part A: Sugammadex 4 mg (6 to <12 Years) | Plasma Clearance (CL) of Sugammadex [Part A] | 3.43 L/hr | Geometric Coefficient of Variation 105 |
| Part A: Sugammadex 4 mg (12 to <17 Years) | Plasma Clearance (CL) of Sugammadex [Part A] | 5.69 L/hr | Geometric Coefficient of Variation 24.1 |
Primary
Plasma Half-Life (t½) of Sugammadex [Part A]
The t½ of sugammadex, defined as the time required for the plasma concentration to decrease to 50% of maximum, was determined in each Part A arm.
Time frame: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
Population: All participants with ≥5 post-dosing samples available are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Plasma Half-Life (t½) of Sugammadex [Part A] | 1.15 Hours |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Plasma Half-Life (t½) of Sugammadex [Part A] | 1.19 Hours |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Plasma Half-Life (t½) of Sugammadex [Part A] | 1.49 Hours |
| Part A: Sugammadex 4 mg (2 to <6 Years) | Plasma Half-Life (t½) of Sugammadex [Part A] | 1.12 Hours |
| Part A: Sugammadex 4 mg (6 to <12 Years) | Plasma Half-Life (t½) of Sugammadex [Part A] | 1.56 Hours |
| Part A: Sugammadex 4 mg (12 to <17 Years) | Plasma Half-Life (t½) of Sugammadex [Part A] | 1.51 Hours |
Primary
Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B]
The time to recovery of TOF ratio to ≥0.9 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. Per protocol, the efficacy analysis is based on comparison of the Part B: Sugammadex 2 mg arm versus the Part B: Neostigmine + (Glycopyrrolate or Atropine) arm.
Time frame: Up to 30 minutes post-dose
Population: All randomized participants in Part B who received ≥1 dose of study drug are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B] | 1.6 Minutes | 95% Confidence Interval 1.3 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B] | 1.9 Minutes | 95% Confidence Interval 1.7 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B] | 7.5 Minutes | 95% Confidence Interval 5.6 |
p-value: <0.000195% CI: [0.16, 0.32]ANOVA
Secondary
Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B]
The time to recovery of TOF ratio to ≥0.7 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB.
Time frame: Up to 30 minutes post-dose
Population: All randomized participants in Part B who received ≥1 dose of study drug are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B] | 1.1 Minutes | 95% Confidence Interval 0.9 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B] | 1.3 Minutes | 95% Confidence Interval 1.1 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B] | 3.7 Minutes | 95% Confidence Interval 2.9 |
Secondary
Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B]
The time to recovery of TOF ratio to ≥0.8 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB.
Time frame: Up to 30 minutes post-dose
Population: All randomized participants in Part B who received ≥1 dose of study drug are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sugammadex 2 mg (2 to <6 Years) | Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B] | 1.3 Minutes | 95% Confidence Interval 1.1 |
| Part A: Sugammadex 2 mg (6 to <12 Years) | Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B] | 1.5 Minutes | 95% Confidence Interval 1.3 |
| Part A: Sugammadex 2 mg (12 to <17 Years) | Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B] | 5.0 Minutes | 95% Confidence Interval 3.8 |