Suspected or Documented Gram-negative Bacterial InfectionPhase 1NCT03230916

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

A Phase 1 study testing IMI/REL FDC in people with Suspected or Documented Gram-negative Bacterial Infection, run by Merck Sharp & Dohme LLC at 33 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 1 day to 17 years
Conditions the study is for: Suspected or Documented Gram-negative Bacterial Infection
What is being tested?: IMI/REL FDC
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 47 participants
Where: 33 sitesin 8 countries
Study dates: 6 Nov 2017to 11 Aug 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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.

Show all 16Show fewer

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.

Trial locations and contacts

33 sites in 8 countries.

Country

City, postcode or hospital

33 sites in 8 countries

United States8 sites

Our Lady of the Lake Hospital ( Site 1304)
Baton Rouge, Louisiana, 70808
Duke University Medical Center ( Site 1317)
Durham, North Carolina, 27710
Arkansas Children's Hospital ( Site 1311)
Little Rock, Arkansas, 72202
Children's Hospital of Orange County ( Site 1301)
Orange, California, 92868
The Children's Hospital of Philadelphia ( Site 1318)
Philadelphia, Pennsylvania, 19104
Rady Children's Hospital-San Diego ( Site 1305)
San Diego, California, 92123
Seattle Childrens Hospital ( Site 1321)
Seattle, Washington, 98105
St. Louis Children's Hospital ( Site 1322)
St Louis, Missouri, 63110

Other trials in United States

Ukraine6 sites

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1214)
Dnipro, Dnipropetrovsk Oblast, 49100
Kharkiv City Children Hospital 16 ( Site 1200)
Kharkiv, Kharkiv Oblast, 61075
Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1213)
Kyiv, Kyivska Oblast, 04050
Odessa Regional Children Clinical Hospital ( Site 1203)
Odesa, Odesa Oblast, 65031
Children City Clinical Hospital ( Site 1215)
Poltava, Poltava Oblast, 36004
Zaporizhzhya Regional Clinical Childrens Hospital ( Site 1202)
Zaporizhzhya, Zaporizhzhia Oblast, 69063

Other trials in Ukraine

Bulgaria5 sites

UMHAT Deva Maria. EOOD ( Site 0209)
Burgas, 8127
MHAT Pazardjik AD ( Site 0208)
Pazardzhik, Pazardzhik, 4400
UMHAT Dr. Georgi Stranski EAD ( Site 0211)
Pleven, 5800
UMHAT Kanev AD ( Site 0203)
Rousse, 7002
UMHAT Kanev AD ( Site 0212)
Rousse, 7002

Other trials in Bulgaria

Norway4 sites

Haukeland Universitetssjukehus ( Site 0902)
Bergen, Vestfold, 5021
Akershus Universitetssykehus HF ( Site 0903)
Loerenskog, Akershus, 1478
Stavanger Universitetssykehus, Helse Stavanger ( Site 0901)
Stavanger, Rogaland, 4011
St. Olavs Hospital ( Site 0900)
Trondheim, Sor-Trondelag, 7006

Other trials in Norway

United Kingdom4 sites

Bristol Royal Hospital for Children ( Site 1101)
Bristol, Bristol, City of, BS2 8AF
St. Georges University Hospital NHS Foundation Trust ( Site 1103)
London, London, City of, SW17 0QT
Great Northern Children s Hospital ( Site 1102)
Newcastle, Newcastle Upon Tyne, NE1 4LP
University Hospital Southampton NHS Foundation Trust ( Site 1100)
Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

Colombia3 sites

Fundacion Valle del Lili ( Site 0300)
Cali, Valle del Cauca Department, 760032
Hospital Pablo Tobon Uribe ( Site 0301)
Medellín, Antioquia, 050034
Hospital General de Medellin Luz Castro de Gutierrez ( Site 0303)
Medellín, Antioquia, 500515

Other trials in Colombia

Poland2 sites

Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi ( Site 1000)
Lodz, Łódź Voivodeship, 91-347
SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1002)
Łomianki, Masovian Voivodeship, 05-092

Other trials in Poland

Greece1 site

General Hospital of Thessaloniki Hippokrateio ( Site 1402)
Thessaloniki, 546 42

Other trials in Greece

About this study

Official title: A Phase 1b, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of MK-7655A in Pediatric Subjects From Birth to Less Than 18 Years of Age With Confirmed or Suspected Gram-negative Infections

Conditions: Suspected or Documented Gram-negative Bacterial Infection
Being tested: IMI/REL FDC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IMI/REL FDCDrug
Also called MK-7655A
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).

Study groups in NCT03230916
Study group	Role	What they receive
IMI/REL FDC	Experimental	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). Receives: Drug: IMI/REL FDC

What is being measured

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

Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞)
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma imipenem (IMI) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
IMI Maximum Concentration (Cmax)
Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
IMI Central Volume of Distribution (Vc)
Central volume of distribution (Vc) of plasma IMI was calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
IMI Clearance (CL)
Systemic clearance (CL) of plasma IMI was calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
IMI Percentage of Time Above the Minimum Concentration (%TMIC)
Percentage of time spent above the minimum inhibitory concentration (%TMIC) of plasma IMI was calculated. %TMIC is defined as the percentage of time (in hours) in which the lowest concentration of a study drug, completely inhibits growth of the specific organism being tested.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Relebactam (REL) AUC0-∞
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma relebactam (REL) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
REL Maximum Concentration (Cmax)
Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
REL Clearance (CL)
Systemic clearance (CL) of plasma REL was calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
REL Central Volume of Distribution (Vc)
Central volume of distribution (Vc) of plasma REL was calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Cilastatin (CIL) AUC0-∞
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma cilastatin (CIL) was not calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
CIL Time to Maximum Concentration (Tmax)
Time to maximum plasma concentration (Tmax) of CIL was determined. Tmax is defined as the time after drug administration at which peak drug concentration in plasma occurs.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
CIL Concentration at End of Infusion (Ceoi)
Concentration at end of infusion (Ceoi) of plasma CIL was determined.
Measured: 30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5
CIL Terminal Half-Life (t1/2)
Terminal half-life (t1/2) of plasma CIL was not calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
CIL Clearance (CL)
Systemic clearance (CL) of plasma CIL was not calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
CIL Volume of Distribution (Vss)
Volume of distribution (Vss) of plasma CIL was not calculated.
Measured: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to12 hrs after start of DI for Cohort 5

Secondary outcomes (2)

Number of Participants Who Experienced an Adverse Event (AE)
Number of participants with one or more AEs was calculated. An AE is defined as any untoward medical occurrence in a participant administered study drug and which may or may not have a causal relationship to the study drug.
Measured: Up to 17 days
Number of Participants Who Discontinued Study Drug Due to an AE
Number of participants who discontinued study drug due to an AE was calculated. An AE is defined as any untoward medical occurrence in a participant administered study drug and which may or may not have a causal relationship to the study drug.
Measured: Day 1

Timeline

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

6 Nov 201711 Aug 2020

First posted27 Jul 2017
Study start6 Nov 2017
Primary completion28 Jul 2020
Study completion11 Aug 2020

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 Suspected or Documented Gram-negative Bacterial InfectionStudies 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.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03230916
Sponsor's protocol ID: 7655A-020
Other IDs: MK-7665A-020, 2016-004328-43, 2016
Status last verified: Jan 2024
First submitted: 17 Jul 2017
Last updated: 6 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 37562063

Study at a glance

From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of MK-7655A in Pediatric Subjects From Birth to Less Than 18 Years of Age With Confirmed or Suspected Gram-negative Infections
ClinicalTrials.gov ID: NCT03230916
Acronym / sponsor ID: 7655A-020
Conditions: Suspected or Documented Gram-negative Bacterial Infection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 6 Nov 2017 (actual)
Primary completion: 28 Jul 2020 (actual)
Study completion: 11 Aug 2020 (actual)
First posted: 27 Jul 2017 (actual)
Results: Posted 13 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
IMI/REL FDC	Experimental	Drug: IMI/REL FDCImipenem/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).

Who may qualify

Ages: 1 day to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (16 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IMI/REL FDCAlso: MK-7655AIMI/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).	Drug	IMI/REL FDC

Primary outcome

Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma imipenem (IMI) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
IMI Maximum Concentration (Cmax)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration.
IMI Central Volume of Distribution (Vc)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Central volume of distribution (Vc) of plasma IMI was calculated.
IMI Clearance (CL)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Systemic clearance (CL) of plasma IMI was calculated.
IMI Percentage of Time Above the Minimum Concentration (%TMIC)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Percentage of time spent above the minimum inhibitory concentration (%TMIC) of plasma IMI was calculated. %TMIC is defined as the percentage of time (in hours) in which the lowest concentration of a study drug, completely inhibits growth of the specific organism being tested.
Relebactam (REL) AUC0-∞
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma relebactam (REL) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
REL Maximum Concentration (Cmax)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration.
REL Clearance (CL)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Systemic clearance (CL) of plasma REL was calculated.
REL Central Volume of Distribution (Vc)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Central volume of distribution (Vc) of plasma REL was calculated.
Cilastatin (CIL) AUC0-∞
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma cilastatin (CIL) was not calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
CIL Time to Maximum Concentration (Tmax)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Time to maximum plasma concentration (Tmax) of CIL was determined. Tmax is defined as the time after drug administration at which peak drug concentration in plasma occurs.
CIL Concentration at End of Infusion (Ceoi)
Time frame: 30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5
Concentration at end of infusion (Ceoi) of plasma CIL was determined.
CIL Terminal Half-Life (t1/2)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Terminal half-life (t1/2) of plasma CIL was not calculated.
CIL Clearance (CL)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5
Systemic clearance (CL) of plasma CIL was not calculated.
CIL Volume of Distribution (Vss)
Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to12 hrs after start of DI for Cohort 5
Volume of distribution (Vss) of plasma CIL was not calculated.

2 secondary outcomes

Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 17 days
Number of Participants Who Discontinued Study Drug Due to an AE
Time frame: Day 1

Results and safety

Results posted to the registry on 13 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: IMI/REL 15/7.5 mg/kg	7	7
Cohort 2: IMI/REL 15/7.5 mg/kg	6	6
Cohort 3: IMI/REL 15/7.5 mg/kg	6	6
Cohort 4: IMI/REL 10/5 mg/kg	4	4
Cohort 4: IMI/REL 15/7.5 mg/kg	4	4
Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg	6	5
Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg	3	3
Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg	2	2
Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg	2	2
Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg	3	3
Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg	4	4

Primary outcome: Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞)

Time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5. Geometric mean (Geometric Coefficient of Variation). Unit: μM*hr

Measure	Cohort 1: IMI/REL 500/250 mg 30-minute Infusion n = 6	Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 1	Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 30-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 60-minute Infusion n = 1	Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 3	Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 3	Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion n = 4	Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 4	Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion n = 6	Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 9
Value	134.7 (19.8)	153.2 (NA)	219.4 (39.2)	139.4 (26.6)	140 (NA)	156 (18.9)	163 (31.2)	95.4 (39.3)	219.2 (39.6)	152.5 (14.1)	271.3 (15.4)

Population analysed: All allocated participants who were compliant with the protocol and had at least 1 post-dose pharmacokinetic (PK) data point available for IMI AUC0-∞

Primary outcome: IMI Maximum Concentration (Cmax)

Measure	Cohort 1: IMI/REL 500/250 mg 30-minute Infusion n = 6	Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 1	Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 30-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 60-minute Infusion n = 1	Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 3	Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 3	Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion n = 4	Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 4	Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion n = 6	Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 9
Value	107.6 (16.4)	126.0 (NA)	123.0 (20.6)	114.2 (9.2)	110.6 (NA)	150.3 (6.7)	125.1 (25.2)	64.9 (29.6)	127.7 (36.0)	79.4 (26.4)	119.8 (16.8)

Population analysed: All allocated participants who were compliant with the protocol and had at least 1 post-dose pharmacokinetic (PK) data point available for IMI Cmax

Primary outcome: IMI Central Volume of Distribution (Vc)

Measure	Cohort 1: IMI/REL 500/250 mg 30-minute Infusion n = 6	Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 1	Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 30-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 60-minute Infusion n = 1	Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 3	Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 3	Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion n = 4	Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 4	Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion n = 6	Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 9
Value	10.27 (16.2)	8.00 (NA)	4.33 (5.2)	9.60 (2.4)	8.70 (NA)	3.49 (19.6)	2.49 (34.6)	2.39 (53.2)	1.52 (35.0)	1.06 (29.6)	0.95 (34.2)

Population analysed: All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI Vc

Primary outcome: IMI Clearance (CL)

Measure	Cohort 1: IMI/REL 500/250 mg 30-minute Infusion n = 6	Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 1	Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 30-minute Infusion n = 2	Cohort 2: IMI/REL 500/250 mg 60-minute Infusion n = 1	Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion n = 3	Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 3	Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion n = 4	Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 4	Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion n = 6	Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion n = 9
Value	12.58 (18.4)	9.60 (NA)	5.25 (9.2)	11.67 (27.6)	11.74 (NA)	5.31 (29.7)	4.43 (45.2)	3.31 (60.1)	1.70 (48.1)	1.10 (26.2)	0.66 (20.4)

Population analysed: All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI CL

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 17 days (AE reporting), up to 19 days (all-cause mortality). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: IMI/REL 15/7.5 mg/kg	0 of 7 (0%)	1 of 7 (14.3%)	0 of 7
Cohort 2: IMI/REL 15/7.5 mg/kg	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Cohort 3: IMI/REL 15/7.5 mg/kg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Cohort 4: IMI/REL 10/5 mg/kg	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Cohort 4: IMI/REL 15/7.5 mg/kg	0 of 4 (0%)	2 of 4 (50%)	0 of 4
Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg	0 of 5 (0%)	1 of 5 (20%)	0 of 5
Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg	0 of 4 (0%)	0 of 4 (0%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 37562063Bradley 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

33 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IMI/REL FDC in people with Suspected or Documented Gram-negative Bacterial Infection, run by Merck Sharp & Dohme LLC at 33 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Ukraine, Bulgaria, Norway, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞) (time frame: 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03230916, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.