Efficacy, Safety, and Pharmacokinetics of Sugammadex for Reversal of Neuromuscular Blockade (NMB) in Pediatric Participants (MK-8616-089)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 4

Conditions: Neuromuscular Blockade

Treatments: Drug: Neostigmine + Glycopyrrolate; Drug: Sugammadex 4 mg/kg; Drug: Neostigmine + Atropine; Drug: Sugammadex 2 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03351608

8616-089

2017-000692-92 (EudraCT Number)

MK-8616-089 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 288 patients

Sex: All

Ages: 2 to 16 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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288 participants in 5 patient groups

Sugammadex 2 mg/kg (Part A)

Experimental group

Description:

Single intravenous (i.v.) bolus of sugammadex at 2 mg/kg.

Treatment:

Drug: Sugammadex 2 mg/kg

Sugammadex 4 mg/kg (Part A)

Experimental group

Description:

Single i.v. bolus of sugammadex at 4 mg/kg.

Treatment:

Drug: Sugammadex 4 mg/kg

Sugammadex 2 mg/kg (Part B)

Experimental group

Description:

Single i.v. bolus of sugammadex at 2 mg/kg.

Treatment:

Drug: Sugammadex 2 mg/kg

Sugammadex 4 mg/kg (Part B)

Experimental group

Description:

Single i.v. bolus of sugammadex at 4 mg/kg.

Treatment:

Drug: Sugammadex 4 mg/kg

Neostigmine (Part B)

Active Comparator group

Description:

Single i.v. bolus containing neostigmine (50 μg/kg; up to 5 mg maximum dose) in combination with either glycopyrrolate (10 μg/kg) or atropine sulfate (20 μg/kg).

Treatment:

Drug: Neostigmine + Atropine

Drug: Neostigmine + Glycopyrrolate