Clinical Trial Page

Summary
EudraCT Number:2017-000693-11
Sponsor's Protocol Code Number:MK-8616-169
National Competent Authority:Belgium - FPS Health-DGM
Clinical Trial Type:EEA CTA
Trial Status:Completed
Date on which this record was first entered in the EudraCT database:2019-04-05
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedBelgium - FPS Health-DGM
A.2EudraCT number2017-000693-11
A.3Full title of the trial
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
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
PK, safety, and efficacy of sugammadex in children aged birth to <2 years
A.3.2Name or abbreviated title of the trial where available
PK, safety, and efficacy of sugammadex in children aged birth to <2 years
A.4.1Sponsor's protocol code numberMK-8616-169
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03351608
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2Functional name of contact pointYuki Mukai
B.5.3 Address:
B.5.3.1Street AddressOne Merck Drive PO Box 100
B.5.3.2Town/ cityWhitehouse Station, New Jersey
B.5.3.3Post code08889-0100
B.5.3.4CountryUnited States
B.5.4Telephone number1732594-5522
B.5.5Fax number1732594-9866
B.5.6E-mailyuki.mukai@merck.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Bridion (sugammadex injection)
D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp and Dohme B.V.
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNSUGAMMADEX SODIUM
D.3.9.1CAS number 343306-79-6
D.3.9.2Current sponsor codeMK-8616
D.3.9.3Other descriptive nameSUGAMMADEX SODIUM
D.3.9.4EV Substance CodeSUB32205
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number100
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name NEOSTIG (Neostigmine Methylsulfate Injection)
D.2.1.1.2Name of the Marketing Authorisation holderCarinopharm GmbH
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNNEOSTIGMINE METHYLSULFATE
D.3.9.3Other descriptive nameNEOSTIGMINE METHYLSULFATE
D.3.9.4EV Substance CodeSUB20700
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.5
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Glycopyrronium Bromide 200 micrograms/ml Injection
D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Limited
D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNGLYCOPYRRONIUM BROMIDE
D.3.9.1CAS number 596-51-0
D.3.9.4EV Substance CodeSUB07951MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.2
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 4
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Atropine sulfate injection
D.2.1.1.2Name of the Marketing Authorisation holderB. Braun Melsungen AG
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNATROPINE SULFATE
D.3.9.1CAS number 55-48-1
D.3.9.4EV Substance CodeSUB00625MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.5
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 5
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Robinul (Glycopyrrolate)
D.2.1.1.2Name of the Marketing Authorisation holderRIEMSER Pharma GmbH
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNGLYCOPYRRONIUM BROMIDE
D.3.9.1CAS number 596-51-0
D.3.9.4EV Substance CodeSUB07951MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.2
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Neuromuscular Blockade reversal
E.1.1.1Medical condition in easily understood language
Male/female participants between the ages of birth to <2 years undergoing clinical procedure requiring a neuromuscular blocking agent (rocuronium or vecuronium).
E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10057286
E.1.2Term Neuromuscular blockade reversal
E.1.2System Organ Class 10042613 - Surgical and medical procedures
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
1. To describe the pharmacokinetic parameters of sugammadex when used for reversal of moderate neuromuscular blockade (NMB) or deep NMB (Part A).
2. To evaluate the time to neuromuscular recovery of sugammadex in comparison to neostigmine for the reversal of moderate NMB (Part B).
3. To evaluate the safety and tolerability of sugammadex (data will be pooled across Part A and Part B of the study)
E.2.2Secondary objectives of the trial
1. To evaluate the time to extubation of sugammadex in comparison to neostigmine for the reversal of moderate neuromuscular blockade (Part B).
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Is categorized as ASA Physical Status Class 1, 2, or 3 as determined by the investigator
2. Has a planned non-emergent surgical procedure or clinical situation (eg, intubation) that requires moderate or deep NMB with either rocuronium or vecuronium
3. Has a surgical procedure or clinical situation that would allow neuromuscular monitoring techniques to be applied for neuromuscular transmission monitoring
4. Is male or female, between birth and <2 years of age at Visit 2
5. The legally acceptable representative for the study participant provides written informed consent/assent for the trial
E.4Principal exclusion criteria
1. Is a preterm infant or neonate <36 weeks gestational age at birth
2. Has any clinically significant condition or situation (eg, 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
3. Has a neuromuscular disorder that may affect NMB and/or trial assessments
4. Is dialysis-dependent or has (or is suspected of having) severe renal insufficiency (defined as estimated glomerular filtration rate [eGFR] <30 ml/min; using revised Schwartz estimate as method of calculation)
5. Has or is suspected of having a family or personal history of malignant hyperthermia
6. 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
7. Is expected to require mechanical ventilation after the procedure
8. 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
9. Use of medication expected to interfere with study treatments given in this trial, as per prescribing information. Rocuronium or vecuronium are concomitant medications to be used per label as adjunct to general anesthesia. Besides rocuronium or vecuronium, a participant must not be administered any other NMBA during the trial, including:
*Other steroidal NMBAs, such as pancuronium
*Nonsteroidal NMBAs such as succinylcholine or benzylisoquinolinium
compound (eg, cisatracurium). (Except in the circumstance that renewed muscle relaxation is needed after administration of study treatment, in which case a non-steroidal NMBA should be administered)
10. 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.
11. 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
12. Is or has an immediate family member (eg, parent/legal guardian, or sibling) who is investigational site or Sponsor staff directly involved with this study
E.5 End points
E.5.1Primary end point(s)
1.Part A. Area Under the Plasma Concentration Time Curve (AUC) for Sugammadex
2.Part A. Plasma Clearance (CL) of Sugammadex
3.Part A. Apparent Volume of Distribution (Vz) for Sugammadex
4.Part A. Apparent Volume of Distribution at Steady State (Vss) for Sugammadex
5.Part A. Maximum Plasma Concentration (Cmax) of Sugammadex
6.Part A. Half-Life (t1/2) of Sugammadex in Plasma
7.Part B. Time to Neuromuscular Recovery
8.Parts A and B. Adverse Event (AEs)

E.5.1.1Timepoint(s) of evaluation of this end point
1.Baseline and 2, 15, 30, 60, 300, and 600 to 720 minutes post-dose
2.Baseline and 2, 15, 30, 60, 300, and 600 to 720 minutes post-dose
3.Baseline and 2, 15, 30, 60, 300, and 600 to 720 minutes post-dose
4.Baseline and 2, 15, 30, 60, 300, and 600 to 720 minutes post-dose
5.Baseline and 2, 15, 30, 60, 300, and 600 to 720 minutes post-dose
6.Baseline and 2, 15, 30, 60, 300, and 600 to 720 minutes post-dose
7. Within Day 1
8. Up to 7 days
E.5.2Secondary end point(s)
1.Part B. Time to Extubation
E.5.2.1Timepoint(s) of evaluation of this end point
1. Within Day 1
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) Yes
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned2
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA4
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Australia
Brazil
Malaysia
United States
Belgium
Denmark
Finland
France
Hungary
Netherlands
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years5
E.8.9.1In the Member State concerned months
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years5
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 126
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) Yes
F.1.1.3.1Number of subjects for this age range: 27
F.1.1.4Infants and toddlers (28 days-23 months) Yes
F.1.1.4.1Number of subjects for this age range: 99
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
Pediatric patients
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state14
F.4.2 For a multinational trial
F.4.2.1In the EEA 40
F.4.2.2In the whole clinical trial 126
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2019-04-25
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2019-08-05
P. End of Trial
P.End of Trial StatusCompleted
P.Date of the global end of the trial2023-09-21

Sponsors and Collaborators

Medical Conditions

Drug Interventions

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