Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036)
- Registration Number
- NCT04223752
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This is a phase 1, open-label, non-comparative, multicenter clinical study to evaluate the safety, tolerability, and pharmacokinetics of ceftolozane/tazobactam (MK-7625A) in pediatric participants with nosocomial pneumonia (NP).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- Is hospitalized and anticipated to receive a minimum of 8 days of concomitant standard-of-care [SOC] antibiotic therapy for proven or suspected NP.
- If male, is abstinent from heterosexual intercourse, or agrees to use contraception during the intervention period and for ≥30 days after the last dose of study intervention.
- If female, is not pregnant or breastfeeding, or is not a woman of childbearing potential (WOCBP), or is a WOCBP using acceptable contraception, is a WOCBP with negative urine or serum pregnancy test within 48 hours of the first dose of study intervention, or is abstinent from heterosexual intercourse.
- Has a documented history of any moderate or severe hypersensitivity (or allergic) reaction to any β-lactam antibacterial.
- Participants 3 months to <18 years of age: has moderate to severe impairment of renal function, defined as an estimated creatinine clearance (CrCL) <50 mL/min/1.73 m2 based on the revised Schwartz equation or requirement for peritoneal dialysis, hemodialysis, or hemofiltration.
- Participants <3 months of age: has CrCL <20 mL/min/1.73 m2 based on the revised Schwartz equation or requirement for peritoneal dialysis, hemodialysis, or hemofiltration.
- Is receiving or is anticipated to receive piperacillin/tazobactam while receiving ceftolozane/tazobactam or has received piperacillin/tazobactam within 24 hours prior to the first dose of ceftolozane/tazobactam.
- Has participated in any clinical study of a therapeutic investigational product within 30 days prior to the first dose of ceftolozane/tazobactam.
- Has previous participation in any study of ceftolozane or ceftolozane/tazobactam.
- Has any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the participant or the quality of study data.
- Has any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure or septic shock.
- Has active immunosuppression.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age Ceftolozane/Tazobactam Participants 7 to \<12 years of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days. Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age Ceftolozane/Tazobactam Participants 3 months to \<2 years of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days. Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age Ceftolozane/Tazobactam Participants 12 to \<18 years of age with nosocomial pneumonia receive intravenous (IV) ceftolozane/tazobactam every 8 hours for 8-14 days. Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age Ceftolozane/Tazobactam Participants 2 to \<7 years of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days. Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age Ceftolozane/Tazobactam Participants from birth to \<3 months of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days.
- Primary Outcome Measures
Name Time Method Percentage of participants with any drug-related AEs Up to 31 days A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered related to the study intervention.
Percentage of participants with any serious AEs (SAEs) Up to 31 days An SAE is any untoward medical consequence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other important medical event.
Percentage of participants with AEs leading to discontinuation of study intervention Up to 14 days An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of participants with any adverse events (AEs) Up to 31 days An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of participants with any drug-related SAEs Up to 31 days A drug-related SAE is any untoward medical consequence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other important medical event, that is considered related to the study intervention.
- Secondary Outcome Measures
Name Time Method Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma tazobactam Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma AUC0-8 of tazobactam will be determined in each group.
Maximum observed concentration during a dosage interval (Cmax) of plasma ceftolozane Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma Cmax of ceftolozane will be determined in each group.
Maximum observed concentration during a dosage interval (Cmax) of plasma tazobactam Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma Cmax of tazobactam will be determined in each group.
Plasma concentrations of ceftolozane Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma concentrations of ceftolozane will be determined in each group.
Elimination half-life (t1/2) of plasma tazobactam Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma t1/2 of tazobactam will be determined in each group.
Volume of distribution (Vd) of plasma ceftolozane Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma Vd of ceftolozane will be determined in each group.
Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma ceftolozane Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma AUC0-8 of ceftolozane will be determined in each group.
Elimination half-life (t1/2) of plasma ceftolozane Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma t1/2 of ceftolozane will be determined in each group.
Volume of distribution (Vd) of plasma tazobactam Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma Vd of tazobactam will be determined in each group.
Clearance (CL) of plasma ceftolozane Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma CL of ceftolozane will be determined in each group.
Clearance (CL) of plasma tazobactam Day 3: 1, between 4-5, and between 7-8 hours after start of infusion The plasma CL of tazobactam will be determined in each group.
Trial Locations
- Locations (24)
Children's Wisconsin ( Site 1321)
🇺🇸Milwaukee, Wisconsin, United States
Mayo Clinic in Rochester, Minnesota ( Site 1322)
🇺🇸Rochester, Minnesota, United States
West Virginia University ( Site 1310)
🇺🇸Morgantown, West Virginia, United States
Sanford Children's Hospital ( Site 1301)
🇺🇸Sioux Falls, South Dakota, United States
SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1205)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
Montefiore Medical Center [Bronx, NY] ( Site 1313)
🇺🇸New York, New York, United States
Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 1602)
🇲🇽Mexico City, Distrito Federal, Mexico
Hospital General de Medellin ( Site 1503)
🇨🇴Medellin, Antioquia, Colombia
Hippokration General Hospital of Thessaloniki ( Site 0400)
🇬🇷Thessaloniki, Kentriki Makedonia, Greece
Hospital Roberto del Río ( Site 1400)
🇨🇱Santiago, Region M. De Santiago, Chile
SA Tallinna Lastehaigla/Tallinn Children's Hospital ( Site 0201)
🇪🇪Tallinn, Harjumaa, Estonia
St. Olga Children City Hospital ( Site 0906)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1203)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Ivano-Frankivsk Regional Children Clinical Hospital ( Site 1204)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Ciensalud Ips S A S ( Site 1501)
🇨🇴Barranquilla, Atlantico, Colombia
Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 1600)
🇲🇽Mexico City, Distrito Federal, Mexico
Morozovskaya Children City Clinical Hospital ( Site 0901)
🇷🇺Moscow, Moskva, Russian Federation
Smolensk Regional Clinical Hospital ( Site 0903)
🇷🇺Smolensk, Smolenskaya Oblast, Russian Federation
Clinica de la Costa S.A.S. ( Site 1500)
🇨🇴Barranquilla, Atlantico, Colombia
Oncomédica S.A.S ( Site 1506)
🇨🇴Montería, Cordoba, Colombia
Hospital Universitario Sant Joan de Deu ( Site 1100)
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Kharkiv City Children Hospital 16 ( Site 1200)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
SA Tartu Ulikooli Kliinikum Lastekliinik ( Site 0200)
🇪🇪Tartu, Tartumaa, Estonia
AdventHealth Orlando ( Site 1318)
🇺🇸Orlando, Florida, United States