Suspected or Documented Gram-negative Bacterial Infection Clinical Trial
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
| Verified date | January 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 47 |
| Est. completion date | August 11, 2020 |
| Est. primary completion date | July 28, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Day to 17 Years |
| Eligibility | 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 ß-lactam agent; or other ß-lactamase inhibitors (BLIs) e.g. tazobactam, sulbactam, clavulanic acid, avibactam. - Female is currently pregnant or breast feeding or has a positive serum ß-human chorionic gonadotropin (ß-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. |
| Country | Name | City | State |
|---|---|---|---|
| Bulgaria | UMHAT Deva Maria. EOOD ( Site 0209) | Burgas | |
| Bulgaria | MHAT Pazardjik AD ( Site 0208) | Pazardjik | Pazardzhik |
| Bulgaria | UMHAT Dr. Georgi Stranski EAD ( Site 0211) | Pleven | |
| Bulgaria | UMHAT Kanev AD ( Site 0203) | Ruse | |
| Bulgaria | UMHAT Kanev AD ( Site 0212) | Ruse | |
| Colombia | Fundacion Valle del Lili ( Site 0300) | Cali | Valle Del Cauca |
| Colombia | Hospital General de Medellin Luz Castro de Gutierrez ( Site 0303) | Medellin | Antioquia |
| Colombia | Hospital Pablo Tobon Uribe ( Site 0301) | Medellin | Antioquia |
| Greece | General Hospital of Thessaloniki Hippokrateio ( Site 1402) | Thessaloniki | |
| Norway | Haukeland Universitetssjukehus ( Site 0902) | Bergen | Vestfold |
| Norway | Akershus Universitetssykehus HF ( Site 0903) | Loerenskog | Akershus |
| Norway | Stavanger Universitetssykehus, Helse Stavanger ( Site 0901) | Stavanger | Rogaland |
| Norway | St. Olavs Hospital ( Site 0900) | Trondheim | Sor-Trondelag |
| Poland | Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi ( Site 1000) | Lodz | Lodzkie |
| Poland | SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1002) | Lomianki | Mazowieckie |
| Ukraine | SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1214) | Dnipro | Dnipropetrovska Oblast |
| Ukraine | Kharkiv City Children Hospital 16 ( Site 1200) | Kharkiv | Kharkivska Oblast |
| Ukraine | Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1213) | Kyiv | Kyivska Oblast |
| Ukraine | Odessa Regional Children Clinical Hospital ( Site 1203) | Odesa | Odeska Oblast |
| Ukraine | Children City Clinical Hospital ( Site 1215) | Poltava | Poltavska Oblast |
| Ukraine | Zaporizhzhya Regional Clinical Childrens Hospital ( Site 1202) | Zaporizhzhya | Zaporizka Oblast |
| United Kingdom | Bristol Royal Hospital for Children ( Site 1101) | Bristol | Bristol, City Of |
| United Kingdom | St. Georges University Hospital NHS Foundation Trust ( Site 1103) | London | London, City Of |
| United Kingdom | Great Northern Children s Hospital ( Site 1102) | Newcastle | Newcastle Upon Tyne |
| United Kingdom | University Hospital Southampton NHS Foundation Trust ( Site 1100) | Southampton | Hampshire |
| United States | Our Lady of the Lake Hospital ( Site 1304) | Baton Rouge | Louisiana |
| United States | Duke University Medical Center ( Site 1317) | Durham | North Carolina |
| United States | Arkansas Children's Hospital ( Site 1311) | Little Rock | Arkansas |
| United States | Children's Hospital of Orange County ( Site 1301) | Orange | California |
| United States | The Children's Hospital of Philadelphia ( Site 1318) | Philadelphia | Pennsylvania |
| United States | St. Louis Children's Hospital ( Site 1322) | Saint Louis | Missouri |
| United States | Rady Children's Hospital-San Diego ( Site 1305) | San Diego | California |
| United States | Seattle Childrens Hospital ( Site 1321) | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Bulgaria, Colombia, Greece, Norway, Poland, Ukraine, United Kingdom,
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 Bacteria — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-8) | Area under the concentration time curve from time 0 to infinity (AUC0-8) of plasma imipenem (IMI) was calculated. AUC0-8 is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | 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 | |
| Primary | IMI Maximum Concentration (Cmax) | Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration. | 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 | |
| Primary | IMI Central Volume of Distribution (Vc) | Central volume of distribution (Vc) of plasma IMI was calculated. | 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 | |
| Primary | IMI Clearance (CL) | Systemic clearance (CL) of plasma IMI was calculated. | 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 | |
| Primary | 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. | 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 | |
| Primary | Relebactam (REL) AUC0-8 | Area under the concentration time curve from time 0 to infinity (AUC0-8) of plasma relebactam (REL) was calculated. AUC0-8 is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | 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 | |
| Primary | REL Maximum Concentration (Cmax) | Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration. | 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 | |
| Primary | REL Clearance (CL) | Systemic clearance (CL) of plasma REL was calculated. | 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 | |
| Primary | REL Central Volume of Distribution (Vc) | Central volume of distribution (Vc) of plasma REL was calculated. | 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 | |
| Primary | Cilastatin (CIL) AUC0-8 | Area under the concentration time curve from time 0 to infinity (AUC0-8) of plasma cilastatin (CIL) was not calculated. AUC0-8 is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | 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 | |
| Primary | 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. | 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 | |
| Primary | CIL Concentration at End of Infusion (Ceoi) | Concentration at end of infusion (Ceoi) of plasma CIL was determined. | 30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5 | |
| Primary | CIL Terminal Half-Life (t1/2) | Terminal half-life (t1/2) of plasma CIL was not calculated. | 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 | |
| Primary | CIL Clearance (CL) | Systemic clearance (CL) of plasma CIL was not calculated. | 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 | |
| Primary | CIL Volume of Distribution (Vss) | Volume of distribution (Vss) of plasma CIL was not calculated. | 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 | 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. | Up to 17 days | |
| Secondary | 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. | Day 1 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03969901 -
Safety, Tolerability, Efficacy and Pharmacokinetics of Imipenem/Cilastatin/Relebactam (MK-7655A) in Pediatric Participants With Gram-negative Bacterial Infection (MK-7655A-021)
|
Phase 2/Phase 3 |