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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 2 to 16 years
• All sexes
• No healthy volunteers
• Child

Trial locations and contacts

30 sites in 8 countries.

About this study

Official title: A Phase 4 Double-Blinded, Randomized, Active Comparator-Controlled Clinical Trial to Study the Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants

Conditions

Neuromuscular Blockade

Being tested

Sugammadex 2 mg/kg, Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate, Neostigmine + Atropine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Sugammadex 2 mg/kgDrug

  Also called MK-8616, BRIDION®

  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.

• Sugammadex 4 mg/kgDrug

  Also called MK-8616, BRIDION®

  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).

• Neostigmine + GlycopyrrolateDrug

  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.

• Neostigmine + AtropineDrug

  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.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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.

   Measured: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose

2. 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.

   Measured: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose

3. 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.

   Measured: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose

4. 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.

   Measured: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose

5. 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.

   Measured: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose

6. 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.

   Measured: Up to 7 days

7. 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.

   Measured: Up to 30 minutes post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted24 Nov 2017
2. Study start12 Feb 2018
3. Primary completion28 Jan 2020
4. Study completion28 Jan 2020

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Publications (1)Papers the sponsor has linked to this study.
• Other trials for Neuromuscular BlockadeStudies of the same condition, open and under way.
• More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.