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
- 41
- 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 Adverse Events (AEs) Up to 31 days An AE was defined as 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. The percentage of participants experiencing any AE was reported for each arm.
Percentage of Participants With Any Serious AEs (SAEs) Up to 31 days An SAE was defined as 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. The percentage of participants with any SAE was reported for each arm.
Percentage of Participants With Any Drug-related AEs Up to 31 days A drug-related AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered related to the study intervention. The percentage of participants with any drug related AEs was reported for each arm.
Percentage of Participants With Any Drug-related SAEs Up to 31 days A drug-related SAE was defined 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. The percentage of participants with any drug related SAEs was reported for each arm.
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention Up to 14 days An AE was defined as 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. The percentage of participants with AEs leading to discontinuation of study intervention was reported for each arm.
- Secondary Outcome Measures
Name Time Method Plasma Concentrations of Ceftolozane Day 3: 1, between 4-5, and between 7-8 hours post start of infusion The plasma concentrations of ceftolozane were determined in each group. Blood samples were collected at pre-specified timepoints to determine the plasma concentrations of ceftolozane in participants receiving ceftolozane/tazobactam.
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 post start of infusion AUC0-8 was defined as a measure of ceftolozane exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at pre-specified timepoints to determine the AUC0-8 of ceftolozane in participants receiving ceftolozane/tazobactam.
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Ceftolozane Day 3: 1, between 4-5, and between 7-8 hours post start of infusion Cmax was defined as the maximum concentration of ceftolozane observed in plasma. Blood samples were collected at pre-specified timepoints to determine the Cmax of ceftolozane in participants receiving ceftolozane/tazobactam.
Elimination Half-life (t1/2) of Plasma Ceftolozane Day 3: 1, between 4-5, and between 7-8 hours post start of infusion Elimination half-life (t1/2) was defined as the time needed to reduce the level of ceftolozane in the blood by one-half (1/2). Blood samples collected at pre-specified timepoints were used to determine the apparent terminal half-life (t1/2) of ceftolozane in participants receiving ceftolozane/tazobactam.
Clearance (CL) of Plasma Ceftolozane Day 3: 1, between 4-5, and between 7-8 hours post start of infusion CL was defined as the total clearance of ceftolozane in plasma over time, assessed as the rate at which ceftolozane was removed from the plasma. Blood samples were collected at pre-specified timepoints to determine the CL of ceftolozane in participants receiving ceftolozane/tazobactam.
Volume of Distribution (Vd) of Plasma Ceftolozane Day 3: 1, between 4-5, and between 7-8 hours post start of infusion Vd was defined as the distributed volume of study drug in plasma at steady state. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug. Blood samples were collected at pre-specified timepoints to determine the Vd of ceftolozane in participants receiving ceftolozane/tazobactam.
Plasma Concentrations of Tazobactam Day 3: 1, between 4-5, and between 7-8 hours post start of infusion The plasma concentrations of tazobactam were determined in each group. Blood samples were collected at pre-specified timepoints to determine the plasma concentrations of tazobactam in participants receiving ceftolozane/tazobactam. No data were calculated for a timepoint if \>50% of samples were below limit of quantification (BLOQ).
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 post start of infusion AUC0-8 was defined as a measure of tazobactam exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at pre-specified timepoints to determine the AUC0-8 of tazobactam in participants receiving ceftolozane/tazobactam.
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Tazobactam Day 3: 1, between 4-5, and between 7-8 hours post start of infusion Cmax was defined as the maximum concentration of tazobactam observed in plasma. Blood samples were collected at pre-specified timepoints to determine the Cmax of tazobactam in participants receiving ceftolozane/tazobactam. The analysis population consisted of participants who received at least 6 doses of ceftolozane/tazobactam and had at least 1 quantifiable plasma concentration of tazobactam.
Elimination Half-life (t1/2) of Plasma Tazobactam Day 3: 1, between 4-5, and between 7-8 hours post start of infusion Elimination half-life (t1/2) was defined as the time needed to reduce the level of tazobactam in the blood by one-half (1/2). Blood samples collected at pre-specified timepoints were used to determine the apparent terminal half-life (t1/2) of tazobactam in participants receiving ceftolozane/tazobactam.
Clearance (CL) of Plasma Tazobactam Day 3: 1, between 4-5, and between 7-8 hours post start of infusion CL was defined as the total clearance of tazobactam in plasma over time, assessed as the rate at which tazobactam was removed from the plasma. Blood samples were collected at pre-specified timepoints to determine the CL of tazobactam in participants receiving ceftolozane/tazobactam.
Volume of Distribution (Vd) of Plasma Tazobactam Day 3: 1, between 4-5, and between 7-8 hours post start of infusion Vd is defined as the distributed volume of study drug in plasma at steady state. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug. Blood samples were collected at pre-specified timepoints to determine the Vd of tazobactam in participants receiving ceftolozane/tazobactam.
Trial Locations
- Locations (24)
AdventHealth Orlando ( Site 1318)
🇺🇸Orlando, Florida, United States
Mayo Clinic in Rochester, Minnesota ( Site 1322)
🇺🇸Rochester, Minnesota, United States
Montefiore Medical Center [Bronx, NY] ( Site 1313)
🇺🇸New York, New York, United States
Sanford Children's Hospital ( Site 1301)
🇺🇸Sioux Falls, South Dakota, United States
West Virginia University ( Site 1310)
🇺🇸Morgantown, West Virginia, United States
Children's Wisconsin ( Site 1321)
🇺🇸Milwaukee, Wisconsin, United States
Hospital Roberto del Río ( Site 1400)
🇨🇱Santiago, Region M. de Santiago, Chile
Hospital General de Medellin ( Site 1503)
🇨🇴Medellín, Antioquia, Colombia
Ciensalud Ips S A S ( Site 1501)
🇨🇴Barranquilla, Atlántico, Colombia
Clinica de la Costa S.A.S. ( Site 1500)
🇨🇴Barranquilla, Atlántico, Colombia
Scroll for more (14 remaining)AdventHealth Orlando ( Site 1318)🇺🇸Orlando, Florida, United States