A Pharmacokinetics Study of MK-7655A in Pediatric Participants With Gram-negative Infections (MK-7655A-020)

NCT ID: NCT03230916

Last Updated: 2024-02-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-06

Study Completion Date

2020-08-11

Brief Summary

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This study aims to obtain plasma pharmacokinetic (PK) data and characterize the PK profile of imipenem (IMI), cilastatin (CIL), and relebactam (REL) following administration of a single intravenous (IV) dose of MK-7655A (a fixed ratio combination of imipenem/cilastatin/relebactam), hereafter referred to as IMI/REL.

Detailed Description

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Conditions

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Suspected or Documented Gram-negative Bacterial Infection

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IMI/REL FDC

Imipenem/Cilastatin/Relebactam (IMI/REL) administered as a single fixed 2:1 ratio of imipenem/cilastatin to relebactam, with a maximum dose of 15 mg/kg IMI and 15 mg/kg CIL (up to 500 mg IMI and 500 mg CIL) and 7.5 mg/kg REL (up to 250 mg REL).

Group Type EXPERIMENTAL

IMI/REL FDC

Intervention Type DRUG

IMI/REL is supplied as a single fixed dose combination (FDC) vial; which is administered at a maximum dose of 15 mg/kg IMI and 15 mg/kg CIL (up to 500 mg IMI and 500 mg CIL) and 7.5 mg/kg REL (up to 250 mg REL).

Interventions

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IMI/REL FDC

IMI/REL is supplied as a single fixed dose combination (FDC) vial; which is administered at a maximum dose of 15 mg/kg IMI and 15 mg/kg CIL (up to 500 mg IMI and 500 mg CIL) and 7.5 mg/kg REL (up to 250 mg REL).

Intervention Type DRUG

Other Intervention Names

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MK-7655A

Eligibility Criteria

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Inclusion Criteria

* Has a parent or legally acceptable representative (LAR) who provides written informed consent for the trial on the participant's behalf.
* Aged from birth to \<18 years old.
* Is hospitalized, currently receiving antibacterial treatment for confirmed or suspected Gram-negative bacterial infection, and expected to require hospitalization until at least 24 hours after completion of study drug administration.
* Is not of reproductive potential; but if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner from the time of consent through 24 hours after completion of study drug administration.
* Has clinically stable renal function at the time of screening that is judged to be within acceptable ranges.
* Has sufficient intravascular access to receive study drug through an existing peripheral or central line.

Exclusion Criteria

* Has a personal history of hypersensitivity to imipenem/cilastatin (IMI) or to any of the following: any carbapenem, cephalosporin, penicillin, or other β-lactam agent; or other β-lactamase inhibitors (BLIs) e.g. tazobactam, sulbactam, clavulanic acid, avibactam.
* Female is currently pregnant or breast feeding or has a positive serum β-human chorionic gonadotropin (β-hCG) pregnancy test.
* Has a history of a seizure disorder requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years.
* Has used or plans to use valproic acid or divalproex sodium within 2 weeks prior to screening or at any point between screening and 24 hours after the completion of study drug infusion.
* Has received treatment or plans to receive treatment with any carbapenem antibiotic within 48 hours prior to initiation of study drug infusion or at any point between administration of study drug and the last PK sample collection.
* Has used or plans to use any of the following medications, which are organic anion transporter (OAT) 1 or OAT3 inhibitors, within 1 week prior to screening or at any point between screening and the last PK sample collection: cimetidine, probenecid, indomethacin, mefenamic acid, furosemide or other loop diuretics (eg, bumetanide, torsemide, ethacrynic acid), angiotensin receptor blockers (eg, valsartan), and ketorolac.
* Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days prior to screening.
* Has enrolled previously in the current trial and been discontinued, or has received REL for any other reason.
* Has a current diagnosis of cystic fibrosis, meningitis, or severe sepsis.
* Is expected to survive less than 72 hours after completion of study drug administration.
* Has a history of clinically significant renal, hepatic, or hemodynamic instability.
* Plans to use cardiopulmonary bypass, extracorporeal membrane oxygenation, hemodialysis, or peritoneal dialysis during the study.
* For participants that are 2 to 17 years of age only: weighs outside of the 5th to 95th percentile based on age.
* Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
* Has a planned blood transfusion within 24 hours of study drug administration or expected before the end of the PK sampling.
* Has had significant blood loss (≥5% of total blood volume) within 4 weeks before the screening visit.
Minimum Eligible Age

1 Day

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Arkansas Children's Hospital ( Site 1311)

Little Rock, Arkansas, United States

Site Status

Children's Hospital of Orange County ( Site 1301)

Orange, California, United States

Site Status

Rady Children's Hospital-San Diego ( Site 1305)

San Diego, California, United States

Site Status

Our Lady of the Lake Hospital ( Site 1304)

Baton Rouge, Louisiana, United States

Site Status

St. Louis Children's Hospital ( Site 1322)

St Louis, Missouri, United States

Site Status

Duke University Medical Center ( Site 1317)

Durham, North Carolina, United States

Site Status

The Children's Hospital of Philadelphia ( Site 1318)

Philadelphia, Pennsylvania, United States

Site Status

Seattle Childrens Hospital ( Site 1321)

Seattle, Washington, United States

Site Status

MHAT Pazardjik AD ( Site 0208)

Pazardzhik, Pazardzhik, Bulgaria

Site Status

UMHAT Deva Maria. EOOD ( Site 0209)

Burgas, , Bulgaria

Site Status

UMHAT Dr. Georgi Stranski EAD ( Site 0211)

Pleven, , Bulgaria

Site Status

UMHAT Kanev AD ( Site 0203)

Rousse, , Bulgaria

Site Status

UMHAT Kanev AD ( Site 0212)

Rousse, , Bulgaria

Site Status

Hospital Pablo Tobon Uribe ( Site 0301)

Medellín, Antioquia, Colombia

Site Status

Hospital General de Medellin Luz Castro de Gutierrez ( Site 0303)

Medellín, Antioquia, Colombia

Site Status

Fundacion Valle del Lili ( Site 0300)

Cali, Valle del Cauca Department, Colombia

Site Status

General Hospital of Thessaloniki Hippokrateio ( Site 1402)

Thessaloniki, , Greece

Site Status

Akershus Universitetssykehus HF ( Site 0903)

Loerenskog, Akershus, Norway

Site Status

Stavanger Universitetssykehus, Helse Stavanger ( Site 0901)

Stavanger, Rogaland, Norway

Site Status

St. Olavs Hospital ( Site 0900)

Trondheim, Sor-Trondelag, Norway

Site Status

Haukeland Universitetssjukehus ( Site 0902)

Bergen, Vestfold, Norway

Site Status

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1002)

Łomianki, Masovian Voivodeship, Poland

Site Status

Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi ( Site 1000)

Lodz, Łódź Voivodeship, Poland

Site Status

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1214)

Dnipro, Dnipropetrovsk Oblast, Ukraine

Site Status

Kharkiv City Children Hospital 16 ( Site 1200)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Site Status

Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1213)

Kyiv, Kyivska Oblast, Ukraine

Site Status

Odessa Regional Children Clinical Hospital ( Site 1203)

Odesa, Odesa Oblast, Ukraine

Site Status

Children City Clinical Hospital ( Site 1215)

Poltava, Poltava Oblast, Ukraine

Site Status

Zaporizhzhya Regional Clinical Childrens Hospital ( Site 1202)

Zaporizhzhya, Zaporizhzhia Oblast, Ukraine

Site Status

Bristol Royal Hospital for Children ( Site 1101)

Bristol, Bristol, City of, United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust ( Site 1100)

Southampton, Hampshire, United Kingdom

Site Status

St. Georges University Hospital NHS Foundation Trust ( Site 1103)

London, London, City of, United Kingdom

Site Status

Great Northern Children s Hospital ( Site 1102)

Newcastle, Newcastle Upon Tyne, United Kingdom

Site Status

Countries

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United States Bulgaria Colombia Greece Norway Poland Ukraine United Kingdom

References

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Bradley JS, Makieieva N, Tondel C, Roilides E, Kelly MS, Patel M, Vaddady P, Maniar A, Zhang Y, Paschke A, Chen LF. Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Children with Confirmed or Suspected Gram-Negative Bacterial Infections: A Phase 1b, Open-Label, Single-Dose Clinical Trial. J Clin Pharmacol. 2023 Dec;63(12):1387-1397. doi: 10.1002/jcph.2334. Epub 2023 Sep 2.

Reference Type RESULT
PMID: 37562063 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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MK-7665A-020

Identifier Type: OTHER

Identifier Source: secondary_id

2016-004328-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7655A-020

Identifier Type: -

Identifier Source: org_study_id

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