E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Reversal of neuromuscular blockade (NMB) |
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E.1.1.1 | Medical condition in easily understood language |
Reversal of neuromuscular blockade in participants undergoing surgery or medical procedure |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018061 |
E.1.2 | Term | General anesthesia |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To describe the pharmacokinetic parameters of sugammadex when used for reversal of moderate NMB or deep NMB (Part A) 2. To evaluate safety and tolerability of sugammadex (data will be pooled across Part A and Part B of the study) 3. To evaluate the efficacy of sugammadex in comparison to neostigmine for the reversal of moderate NMB (Part B) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of sugammadex in comparison to neostigmine for the reversal of moderate NMB (Part B) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must be categorized as ASA Physical Status Class 1, 2, or 3, as determined by the investigator 2. Have a planned non-emergent surgical procedure or clinical situation (eg, intubation) that requires moderate or deep NMB with either rocuronium or vecuronium 3. 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 4. Age between 2 to <17 years at Visit 2. 5. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 7 days after the last dose of study treatment 6. The participant (and/or legally acceptable representative, if applicable) provides written informed consent/assent for the trial |
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E.4 | Principal exclusion criteria |
1. 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 2. Has a neuromuscular disorder that may affect NMB and/or trial assessments 3. Is dialysis-dependent or has (or is suspected of having) severe renal insufficiency (defined as estimated glomerular filtration rate (eGFR) <30 ml/min; using revised Schwartz estimate as method of calculation) 4. Has or is suspected of having a family or personal history of malignant hyperthermia 5. 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 6. 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 7. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment. If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive 8. Use of medication expected to interfere with study treatments given in this trial, as per prescribing information 9. Has been previously treated with sugammadex or has participated in a sugammadex clinical trial 10. 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 11. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Part A only- Pharmacokinetic: Area under the plasma concentration-time curve (AUC), clearance (CL), volume of distribution (Vz), maximum plasma concentration (Cmax), and half-life (t1/2) 2. Part A and Part B- Safety: Adverse event (AE) reporting, laboratory and vital sign assessments. Events of clinical interest: clinically relevant bradycardia, hypersensitivity and anaphylaxis. 3. Part B only - Efficacy: The time to recovery to a train-of-four (TOF) ratio of ≥0.9 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. PK samples collected at 2, 15, 30, 60 mi., 5 and 10 hours post-administration of study drug 2. AEs reported throughout participation in the study (~ 28 days). Safety laboratory assessments at Day1 (peri-anesthetic period) and Day 1 to 2 (post-treatment). Vital signs assessments on Day 1: Prior to administration of NMBA; Prior to administration of study treatment; and 2, 5, 10 and 30 min. after study treatment. 3. Neuromuscular monitoring will be performed using a TOF-Watch SX®. After induction of anesthesia, neuromuscular monitoring will start before the administration of neuromuscular blocking agent. Neuromuscular monitoring should remain ongoing until the participant reaches the endpoint of TOF ≥0.9, or for at least 30 min. following administration of a single dose of study drug |
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E.5.2 | Secondary end point(s) |
1. The time to recovery to a TOF ratio of ≥0.8 2. The time to recovery to a TOF ratio of ≥0.7 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Neuromuscular monitoring will be performed using a TOF-Watch SX®. After induction of anesthesia, neuromuscular monitoring will start before the administration of neuromuscular blocking agent. Neuromuscular monitoring should remain ongoing until the participant reaches the endpoint of TOF ratio ≥0.8, or for at least 30 minutes following administration of a single dose of study drug. 2. Neuromuscular monitoring will be performed using a TOF-Watch SX®. After induction of anesthesia, neuromuscular monitoring will start before the administration of neuromuscular blocking agent. Neuromuscular monitoring should remain ongoing until the participant reaches the endpoint of TOF ratio ≥0.7, or for at least 30 minutes following administration of a single dose of study drug. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Denmark |
Finland |
Germany |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |