Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants Aged Birth to <2 Years (MK-8616-169)

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 1 day to 2 years
• All sexes
• No healthy volunteers
• Child

Trial locations and contacts

39 sites in 14 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 Aged Birth to <2 Years

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

  For moderate NMB reversal, a single IV 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 train-of-four (TOF) stimulations.

• Sugammadex 4 mg/kgDrug

  Also called MK-8616

  For deep NMB reversal, a single IV 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 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 T2 in response to TOF stimulations.

What is being measured

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

1. Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) for Sugammadex

   Pharmacokinetic (PK) blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine AUC0-inf for sugammadex. As pre-specified by the Statistical Analysis Plan (SAP) for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose

2. Part A: Area Under the Plasma Concentration Time Curve up to the Interpolated Concentration at 1 Hour Post Dose (AUC0-1hr) for Sugammadex

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine AUC0-1hr for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, and 60 minutes (1 hour) post-dose

3. Part A: Area Under the Plasma Concentration Time Curve up to the Interpolated Concentration at 4 Hours Post Dose (AUC0-4hr) for Sugammadex

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine AUC0-4hr for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, and 240 minutes (4 hours) post-dose

4. Part A: Maximum Plasma Concentration (Cmax) of Sugammadex

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine Cmax for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose

5. Part A: Plasma Clearance (CL) of Sugammadex

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine CL for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose

6. Part A: Apparent Volume of Distribution (Vd) for Sugammadex

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine Vd for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose

7. Apparent Volume of Distribution at Steady State (Vss) for Sugammadex

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine Vss for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose

8. Part A: Half-Life (t1/2) of Sugammadex in Plasma

   PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine t½ for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to <27 days, 28 days to <3 months, 3 to <6 months, and 6 months to < 2 years) for each dose (2 mg and 4 mg).

   Measured: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose

9. Part B: Time to Neuromuscular Recovery (TTNMR) In Reversal of Moderate Block

   Time to neuromuscular recovery was defined as the interval from administration of reversal agent to time to neuromuscular recovery. TTNMR could be assessed by 1 of 4 methods selected by the investigator, based on their judgment of what was technically feasible and clinically appropriate for the participant's procedure. These methods were inclusive of both clinical signs (head lift or hip flexion) and neuromuscular transmission monitoring using either a standard peripheral nerve stimulator or the technically challenging quantitative neuromuscular monitoring to train-of-four (TOF) ratio ≥0.9. As pre-specified by the protocol and SAP, TTNMR was analyzed only in Part B participants under the setting of moderate block for comparison of sugammadex 2 mg to neostigmine.

   Measured: Within Day 1

10. Parts A and B: Percentage of Participants With Adverse Events (AEs) Up To 7 Days Post Administration of Study Medication

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified by the protocol and SAP, the primary analysis of safety combined data across Part A and Part B (and across age cohorts) and included all AEs that occurred up to 7 days post administration of study medication. The percentage of participants with an AE was reported by treatment and dose received.

    Measured: Up to Day 7

Timeline

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

1. First posted9 Apr 2019
2. Study start23 Jul 2019
3. Primary completion21 Sep 2023
4. Study completion21 Sep 2023

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.