Clinical trial NCT04223752: Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nosocomial Pneumonia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-01-10
Enrollment: 40
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of participants with any adverse events (AEs)
timeFrame: Up to 31 days
measure: Percentage of participants with any serious AEs (SAEs)
timeFrame: Up to 31 days
measure: Percentage of participants with any drug-related AEs
timeFrame: Up to 31 days
measure: Percentage of participants with any drug-related SAEs
timeFrame: Up to 31 days
measure: Percentage of participants with AEs leading to discontinuation of study intervention
timeFrame: Up to 14 days
Secondary outcomes:
measure: Plasma concentrations of ceftolozane
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma ceftolozane
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma tazobactam
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Maximum observed concentration during a dosage interval (Cmax) of plasma ceftolozane
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Maximum observed concentration during a dosage interval (Cmax) of plasma tazobactam
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Elimination half-life (t1/2) of plasma ceftolozane
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Elimination half-life (t1/2) of plasma tazobactam
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Volume of distribution (Vd) of plasma ceftolozane
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Volume of distribution (Vd) of plasma tazobactam
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Clearance (CL) of plasma ceftolozane
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
measure: Clearance (CL) of plasma tazobactam
timeFrame: Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth Orlando ( Site 1318)
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota ( Site 1322)
state: Minnesota
city: New York
country: United States
facility: Montefiore Medical Center [Bronx, NY] ( Site 1313)
state: New York
city: Sioux Falls
country: United States
facility: Sanford Children's Hospital ( Site 1301)
state: South Dakota
city: Morgantown
country: United States
facility: West Virginia University ( Site 1310)
state: West Virginia
city: Milwaukee
country: United States
facility: Children's Wisconsin ( Site 1321)
state: Wisconsin
city: Santiago
country: Chile
facility: Hospital Roberto del Río ( Site 1400)
state: Region M. De Santiago
city: Medellin
country: Colombia
facility: Hospital General de Medellin ( Site 1503)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Ciensalud Ips S A S ( Site 1501)
state: Atlantico
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S. ( Site 1500)
state: Atlantico
city: Montería
country: Colombia
facility: Oncomédica S.A.S ( Site 1506)
state: Cordoba
city: Tallinn
country: Estonia
facility: SA Tallinna Lastehaigla/Tallinn Children's Hospital ( Site 0201)
state: Harjumaa
city: Tartu
country: Estonia
facility: SA Tartu Ulikooli Kliinikum Lastekliinik ( Site 0200)
state: Tartumaa
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki ( Site 0400)
state: Kentriki Makedonia
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 1602)
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 1600)
state: Distrito Federal
city: Moscow
country: Russian Federation
facility: Morozovskaya Children City Clinical Hospital ( Site 0901)
state: Moskva
city: Saint-Petersburg
country: Russian Federation
facility: St. Olga Children City Hospital ( Site 0906)
state: Sankt-Peterburg
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital ( Site 0903)
state: Smolenskaya Oblast
city: Esplugues de Llobregat
country: Spain
facility: Hospital Universitario Sant Joan de Deu ( Site 1100)
state: Barcelona
city: Dnipro
country: Ukraine
facility: SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1205)
state: Dnipropetrovska Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Children Clinical Hospital ( Site 1204)
state: Ivano-Frankivska Oblast
city: Kharkiv
country: Ukraine
facility: Kharkiv City Children Hospital 16 ( Site 1200)
state: Kharkivska Oblast
city: Kyiv
country: Ukraine
facility: Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1203)
state: Kyivska Oblast
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: