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

NCT03909165 | Completed Phase 4 Results DMC FDA Drug

• 3 other identifiers: 8616-169MK-8616-1692017-000693-11
• Study Type: interventional
• Target: 145
• Locations: 14 countries
• Sites: 39

Brief Summary

This study will evaluate the efficacy, safety, and pharmacokinetics (PK) of sugammadex (MK-8616) for reversal of both moderate and deep neuromuscular blockade (NMB) in pediatric participants aged birth to \<2 years. The primary hypothesis of this study is that sugammadex is superior to neostigmine in reversing moderate NMB as measured by time to neuromuscular recovery.

Conditions

Neuromuscular Blockade

Outcome Measures

Primary Outcomes (10)

• 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).

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

• 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).

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

• 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).

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

• 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).

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

• 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).

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

• 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).

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

• 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).

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

• 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).

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

• 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.

  Within Day 1

• 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.

  Up to Day 7

Secondary Outcomes (1)

• Part B: Time to Extubation In Reversal of Moderate Block

  Within Day 1

Study Arms (5)

Part A. Sugammadex 2 mg/kg

EXPERIMENTAL

Participants received a single intravenous (IV) bolus of sugammadex at 2 mg/kg for moderate NMB reversal.

Drug: Sugammadex 2 mg/kg

Part A. Sugammadex 4 mg/kg

EXPERIMENTAL

Participants received a single IV bolus of sugammadex at 4 mg/kg for deep NMB reversal.

Drug: Sugammadex 4 mg/kg

Part B. Sugammadex 2 mg/kg

EXPERIMENTAL

Participants received a single IV bolus of sugammadex at 2 mg/kg for moderate NMB reversal.

Drug: Sugammadex 2 mg/kg

Part B. Sugammadex 4 mg/kg

EXPERIMENTAL

Participants received a single IV bolus of sugammadex at 4 mg/kg for deep NMB reversal.

Drug: Sugammadex 4 mg/kg

Part B. Neostigmine

ACTIVE COMPARATOR

Participants received a single IV 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) based on availability and/or contraindications, for moderate NMB reversal.

Drug: Neostigmine + Glycopyrrolate; Drug: Neostigmine + Atropine

Interventions

Sugammadex 2 mg/kg DRUG

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.

Also known as: MK-8616

Part A. Sugammadex 2 mg/kg; Part B. Sugammadex 2 mg/kg

Sugammadex 4 mg/kg DRUG

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).

Also known as: MK-8616

Part A. Sugammadex 4 mg/kg; Part B. Sugammadex 4 mg/kg

Neostigmine + Glycopyrrolate DRUG

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.

Part B. Neostigmine

Neostigmine + Atropine DRUG

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.

Part B. Neostigmine

Eligibility Criteria

• Age: 1 Day - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1, 2, or 3.
• Has a planned non-emergent surgical procedure or clinical situation (e.g., intubation) that requires moderate or deep NMB with either rocuronium or vecuronium.
• Has a surgical procedure or clinical situation that would allow neuromuscular monitoring techniques to be applied for neuromuscular transmission monitoring.
• Is male or female, between birth and \<2 years of age.

You may not qualify if:

• Is a preterm infant or neonate \<36 weeks gestational age at birth.
• Has any clinically significant condition or situation (e.g., anatomical malformation that complicates intubation) other than the condition requiring the use of NMBA 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.
• 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.
• Is expected to require mechanical ventilation after the procedure.
• 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.
• Use of medication expected to interfere with study treatments given in this trial.
• Has been previously treated with sugammadex or has participated in a sugammadex clinical trial within 30 days of signing the informed consent form of this current 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (39)

Lucille Packard Children's Hospital ( Site 3008)

Palo Alto, California, 94304, United States

Location

Variety Children's Hospital D.B.A. Nicklaus Children's Hospital ( Site 3019)

Miami, Florida, 33155, United States

Location

OU Medical Center ( Site 3005)

Oklahoma City, Oklahoma, 73104, United States

Location

The Children's Hospital of Philadelphia ( Site 3021)

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh UPMC ( Site 3017)

Pittsburgh, Pennsylvania, 15224, United States

Location

McGovern Medical School at UT Health/ Memorial Hermann ( Site 3014)

Houston, Texas, 77030, United States

Location

University of Vermont Medical Center ( Site 3013)

Burlington, Vermont, 05401, United States

Location

The Children s Hospital at Westmead ( Site 3805)

Westmead, New South Wales, 2145, Australia

Location

Queensland Children s Hospital ( Site 3806)

South Brisbane, Queensland, 4101, Australia

Location

Royal Childrens Hospital Melbourne ( Site 3801)

Parkville, Victoria, 3052, Australia

Location

Universitaire Ziekenhuis Antwerpen - UZA ( Site 3200)

Edegem, Antwerpen, 2650, Belgium

Location

UZ Brussel ( Site 3201)

Brussels, Bruxelles-Capitale, Region de, 1090, Belgium

Location

UZ Leuven - Campus Gasthuisberg ( Site 3202)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Hospital Pequeno Principe ( Site 3826)

Curitiba, Paraná, 80250-060, Brazil

Location

Hospital Tacchini ( Site 3827)

Bento Gonçalves, Rio Grande do Sul, 95700-084, Brazil

Location

Instituto da Crianca do Hospital das Clinicas-FMUSP ( Site 3825)

São Paulo, 05403-900, Brazil

Location

Rigshospitalet ( Site 3250)

Copenhagen, Capital Region, 2100, Denmark

Location

New Childrens Hospital ( Site 3750)

Helsinki, Uusimaa, 00029, Finland

Location

C.H.R.U. de Lille. Hopital Jeanne de Flandres ( Site 3304)

Lille, Nord, 59000, France

Location

Unidad de Cirugía Cardiovascular ( Site 4126)

Guatemala City, 01011, Guatemala

Location

Szegedi Tudomanyegyetem ( Site 4201)

Szeged, Csongrád megye, 6720, Hungary

Location

Debreceni Egyetem Klinikai Kozpont ( Site 4200)

Debrecen, 4032, Hungary

Location

Sarawak General Hospital ( Site 3877)

Kuching, Sarawak, 93586, Malaysia

Location

Women and Children Hospital Kuala Lumpur (Hospital Tunku Azizah) ( Site 3875)

Kuala Lumpur, 50300, Malaysia

Location

University Malaya Medical Centre. ( Site 3876)

Kuala Lumpur, 59100, Malaysia

Location

Hospital General de Zona No. 1 ( Site 4153)

Ciudad de Villa de Álvarez, Colima, 28984, Mexico

Location

Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 4152)

Aguascalientes, 20259, Mexico

Location

Radboud University Medical Center ( Site 4226)

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Erasmus University Medical Center ( Site 4225)

Rotterdam, South Holland, 3015 GD, Netherlands

Location

University Medical Center Groningen ( Site 4227)

Groningen, 9713 GZ, Netherlands

Location

Wilhelmina Kinderziekenhuis ( Site 4228)

Utrecht, 3584 EA, Netherlands

Location

Instituto Nacional Cardiovascular Incor ( Site 3928)

Lima, 15072, Peru

Location

Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 4288)

Kemerovo, Kemerovo Oblast, 650002, Russia

Location

NMRC Obstetrics Gynecology and Perinatology n.a. V.I. Kulakov ( Site 4287)

Moscow, Moscow, 117997, Russia

Location

Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 4275)

Moscow, Moscow, 117997, Russia

Location

Children City Clinical Hospital 13 n.a N.F.Filatov ( Site 4285)

Moscow, Moscow, 123001, Russia

Location

Children City Clinical Hospital #9 n.a. G.N.Speransky ( Site 4290)

Moscow, Moscow, 123317, Russia

Location

Scientific-Research Clinical Pediatric Institution n.a. Veltischev ( Site 4276)

Moscow, Moscow, 125412, Russia

Location

St.Petersburg State Pediatric Medical University ( Site 4281)

Saint Petersburg, Sankt-Peterburg, 194100, Russia

Location

Related Publications (1)

• Mensah-Osman E, Mukai Y, Wang A, Matuszczak M, Saldien V, Leibensperger H, Speek M, Locco A, Wrishko R, Gee A, Herring WJ. Sugammadex for Reversal of Neuromuscular Blockade in Neonates and Infants Less than 2 Years Old: Results from a Phase IV Randomized Clinical Trial. Anesthesiology. 2025 Aug 1;143(2):300-312. doi: 10.1097/ALN.0000000000005535. Epub 2025 May 5.

  PMID: 40324166 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

Sugammadex; Neostigmine; Glycopyrrolate; Atropine

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A will be open-label, while Part B will be double-blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 9, 2019
• Study Start: July 23, 2019
• Primary Completion: September 21, 2023
• Study Completion: September 21, 2023
• Last Updated: July 25, 2025
• Results First Posted: September 26, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

NL (4); BR (3); DK (1); GU (1); PE (1); FI (1); HU (2); RU (7); US (7); BE (3); MY (3); ME (2); AU (3); FR (1)