Clinical trial NCT03909165: Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants Aged Birth to <2 Years (MK-8616-169)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neuromuscular Blockade
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-04-09
Enrollment: 145
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This trial will be conducted in two parts: Part A and Part B. In Part A, PK sampling will be conducted to identify the pediatric dose providing sugammadex exposure comparable to the next oldest age cohort. For Part B participants, the efficacy of sugammadex (i.e. neuromuscular recovery / time to extubation) 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) for Sugammadex
timeFrame: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
measure: Part A: Area Under the Plasma Concentration Time Curve up to the Interpolated Concentration at 1 Hour Post Dose (AUC0-1hr) for Sugammadex
timeFrame: Day 1: 2, 15, 30, and 60 minutes (1 hour) post-dose
measure: Part A: Area Under the Plasma Concentration Time Curve up to the Interpolated Concentration at 4 Hours Post Dose (AUC0-4hr) for Sugammadex
timeFrame: Day 1: 2, 15, 30, 60, and 240 minutes (4 hours) post-dose
measure: Part A: Maximum Plasma Concentration (Cmax) of Sugammadex
timeFrame: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
measure: Part A: Plasma Clearance (CL) of Sugammadex
timeFrame: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
measure: Part A: Apparent Volume of Distribution (Vd) for Sugammadex
timeFrame: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
measure: Apparent Volume of Distribution at Steady State (Vss) for Sugammadex
timeFrame: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
measure: Part A: Half-Life (t1/2) of Sugammadex in Plasma
timeFrame: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
measure: Part B: Time to Neuromuscular Recovery (TTNMR) In Reversal of Moderate Block
timeFrame: Within Day 1
measure: Parts A and B: Percentage of Participants With Adverse Events (AEs) Up To 7 Days Post Administration of Study Medication
timeFrame: Up to Day 7
Secondary outcomes:
measure: Part B: Time to Extubation In Reversal of Moderate Block
timeFrame: Within Day 1
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucille Packard Children's Hospital ( Site 3008)
state: California
city: Miami
country: United States
facility: Variety Children's Hospital D.B.A. Nicklaus Children's Hospital ( Site 3019)
state: Florida
city: Oklahoma City
country: United States
facility: OU Medical Center ( Site 3005)
state: Oklahoma
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia ( Site 3021)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh UPMC ( Site 3017)
state: Pennsylvania
city: Houston
country: United States
facility: McGovern Medical School at UT Health/ Memorial Hermann ( Site 3014)
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center ( Site 3013)
state: Vermont
city: Westmead
country: Australia
facility: The Children s Hospital at Westmead ( Site 3805)
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children s Hospital ( Site 3806)
state: Queensland
city: Parkville
country: Australia
facility: Royal Childrens Hospital Melbourne ( Site 3801)
state: Victoria
city: Edegem
country: Belgium
facility: Universitaire Ziekenhuis Antwerpen - UZA ( Site 3200)
state: Antwerpen
city: Brussels
country: Belgium
facility: UZ Brussel ( Site 3201)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg ( Site 3202)
state: Vlaams-Brabant
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe ( Site 3826)
state: Parana
city: Bento Goncalves
country: Brazil
facility: Hospital Tacchini ( Site 3827)
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Instituto da Crianca do Hospital das Clinicas-FMUSP ( Site 3825)
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 3250)
state: Hovedstaden
city: Helsinki
country: Finland
facility: New Childrens Hospital ( Site 3750)
state: Uusimaa
city: Lille
country: France
facility: C.H.R.U. de Lille. Hopital Jeanne de Flandres ( Site 3304)
state: Nord
city: Guatemala
country: Guatemala
facility: Unidad de Cirugía Cardiovascular ( Site 4126)
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem ( Site 4201)
state: Csongrad
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ( Site 4200)
city: Kuching
country: Malaysia
facility: Sarawak General Hospital ( Site 3877)
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Women and Children Hospital Kuala Lumpur (Hospital Tunku Azizah) ( Site 3875)
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre. ( Site 3876)
city: Villa De Alvarez
country: Mexico
facility: Hospital General de Zona No. 1 ( Site 4153)
state: Colima
city: Aguascalientes
country: Mexico
facility: Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 4152)
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center ( Site 4226)
state: Gelderland
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center ( Site 4225)
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen ( Site 4227)
city: Utrecht
country: Netherlands
facility: Wilhelmina Kinderziekenhuis ( Site 4228)
city: Lima
country: Peru
facility: Instituto Nacional Cardiovascular Incor ( Site 3928)
city: Kemerovo
country: Russian Federation
facility: Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 4288)
state: Kemerovskaya Oblast
city: Moscow
country: Russian Federation
facility: NMRC Obstetrics Gynecology and Perinatology n.a. V.I. Kulakov ( Site 4287)
state: Moskva
city: Moscow
country: Russian Federation
facility: Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 4275)
state: Moskva
city: Moscow
country: Russian Federation
facility: Children City Clinical Hospital 13 n.a N.F.Filatov ( Site 4285)
state: Moskva
city: Moscow
country: Russian Federation
facility: Children City Clinical Hospital #9 n.a. G.N.Speransky ( Site 4290)
state: Moskva
city: Moscow
country: Russian Federation
facility: Scientific-Research Clinical Pediatric Institution n.a. Veltischev ( Site 4276)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: St.Petersburg State Pediatric Medical University ( Site 4281)
state: Sankt-Peterburg
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: