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Ceftolozane/Tazobactam 1000

Phase 1

Proven or Suspected Gram-negative Bacterial Infection | Small molecule | Infectious Disease |Merck & Company, Inc.|Last Updated: Sep 11, 2019

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment43

FDA Designations

No designations recorded

Clinical trial landscape

Ceftolozane/Tazobactam 1000 · 1 trial · 2 indications

Phase 1 1
NCT02266706Pharmacokinetic and Safety Study of Ceftolozane/Tazobactam in Pediatric Participants Receiving Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis (MK-7625A-010)Proven or Suspected Gram-negative Bacterial Infection
COMPLETED43 Analytics
PHASE1COMPLETED
Pharmacokinetic and Safety Study of Ceftolozane/Tazobactam in Pediatric Participants Receiving Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis (MK-7625A-010)
Proven or Suspected Gram-negative Bacterial InfectionUnlock trial analytics

Study Endpoints

Primary Endpoints

Maximum Plasma Concentration (Cmax) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Cmax of ceftolozane. Cmax is expressed as geometric least-squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.

Maximum Plasma Concentration (Cmax) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Cmax of tazobactam. Cmax is expressed as geometric least-squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.

Time to Maximum Plasma Concentration (Tmax) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Tmax of ceftolozane.

Time to Maximum Plasma Concentration (Tmax) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Tmax of tazobactam.

Plasma Concentration at the Last Quantifiable Concentration (Clast) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Clast of ceftolozane. Clast is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Plasma Concentration at the Last Quantifiable Concentration (Clast) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Clast of tazobactam. Clast is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Time of Last Sampling Point (Tlast) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Tlast of ceftolozane.

Time of Last Sampling Point (Tlast) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Tlast of tazobactam.

Area Under the Plasma Concentration-Time Curve (AUClast) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of AUC from time zero to the last quantifiable concentration of ceftolozane. AUC0-last is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.

Area Under the Plasma Concentration-Time Curve (AUClast) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of AUC from time zero to the last quantifiable concentration of tazobactam. AUC0-last is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.

Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of AUC from time zero extrapolated to infinity of ceftolozane. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.

Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of AUC from time zero extrapolated to infinity of tazobactam. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.

Elimination Half-life (t1/2) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of t1/2 of ceftolozane. t1/2 is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Elimination Half-life (t1/2) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of t1/2 of tazobactam. t1/2 is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Volume of Distribution at Steady State (Vss) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Vss of ceftolozane. Vss is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Volume of Distribution at Steady State (Vss) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of Vss of tazobactam. Vss is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Plasma Clearance (CL) of Ceftolozane
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of CL of ceftolozane. CL is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Plasma Clearance (CL) of Tazobactam
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Blood was collected for the determination of CL of tazobactam. CL is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100\*sqrt(exp(s\^2)-1), where s\^2 is the observed between-subjects variance on the natural log-scale.

Secondary Endpoints

Number of Participants With One or More Adverse Events
Up to Day 10
Number of Participants Who Discontinued the Study Due to an Adverse Event
Up to Day 10
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort 1: ≥12 to <18 years TOL/TAZ 1000/500 mg FDCEXPERIMENTALParticipants ≥12 to \<18 years of age received a single dose of ceftolozane/tazobactam (TOL/TAZ) 1000/500 mg FDC as a 60-minute infusion on Day 1.
Cohort 2: ≥7 to <12 years TOL/TAZ 18/9 mg/kgEXPERIMENTALParticipants ≥7 to \<12 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1.
Cohort 3: ≥2 to <7 years TOL/TAZ 18/9 or 30/15 mg/kgEXPERIMENTALParticipants ≥2 to \<7 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1. Participants in this cohort enrolled after interim analysis for Cohort 3 received TOL/TAZ 30/15 mg/kg.
Cohort 4: ≥3 months to <2 years TOL/TAZ 18/9 or 30/15 mg/kgEXPERIMENTALParticipants ≥3 months to \<2 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1. Participants in this cohort enrolled after interim analysis for Cohort 3 received TOL/TAZ 30/15 mg/kg.
Cohort 5: birth to <3 months TOL/TAZ 20/10 mg/kgEXPERIMENTALParticipants from birth (\>32 weeks gestation, 7 days postnatal) to \<3 months of age received a single dose of TOL/TAZ 20/10 mg/kg as a 60-minute infusion on Day 1. After interim analysis for Cohort 4, the original regimen of TOL/TAZ 12/6 mg/kg was changed to TOL/TAZ 20/10.
Cohort 6: birth to <3 months TOL/TAZ 12/6 or 20/10 mg/kgEXPERIMENTALParticipants from birth (≤32 weeks gestation, 7 days postnatal) to \<3 months of age with creatinine clearance =20 - 49 mL/min/1.73 m\^2 received a single dose of TOL/TAZ 12/6 mg/kg as a 60-minute infusion on Day 1; participants with creatinine clearance ≥50 mL/min/1.73 m\^2 received a single dose of TOL/TAZ 20/10 mg/kg as a 60-minute infusion on Day 1. After interim analysis for Cohort 4, the original regimen of TOL/TAZ 12/6 was changed to TOL/TAZ 20/10 mg/kg for participants with creatinine clearance ≥50 mL/min/1.73 m\^2.

Interventions

NameTypeDescription
Ceftolozane/Tazobactam 1000/500 mgDRUGA fixed dose combination (FDC) of 1000 mg ceftolozane and 500 mg tazobactam as a 60 minute infusion.
Ceftolozane/Tazobactam 30/15 mg/kgDRUGA FDC of 30 mg/kg of ceftolozane and 15 mg/kg of tazobactam as a 60 minute infusion.
Ceftolozane/Tazobactam 20/10 mg/kgDRUGA FDC of 20 mg/kg of ceftolozane and 10 mg/kg of tazobactam as a 60 minute infusion.
Ceftolozane/Tazobactam 18/9 mg/kgDRUGA FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.
Ceftolozane/Tazobactam 12/6 mg/kgDRUGA FDC of 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam as a 60 minute infusion.
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Eligibility Criteria

Age Range7 Days to 17 Years
SexALL
Healthy VolunteersNo

Key Inclusion Criteria: 1. Males or non-pregnant females from birth to \<18 years of age 2. Receiving standard of care antibiotic therapy for suspected or diagnosed Gram-negative infection or for peri-operative prophylaxis 3. Groups 1-4: Calculated creatinine clearance rate (CLCR) ≥ 80 ml/min/1.73m...

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Frequently asked questions about Ceftolozane/Tazobactam 1000

What is Ceftolozane/Tazobactam used for?

Ceftolozane/Tazobactam is an investigational small molecule being developed for critically ill patients with proven or suspected Gram-negative bacterial infections, including complicated urinary tract infections, complicated intra-abdominal infections, nosocomial pneumonia, and healthcare-associated pneumonia. It is a combination antibiotic being studied in infectious disease.

Who makes Ceftolozane/Tazobactam?

Ceftolozane/Tazobactam is being developed by Merck & Company, Inc., which trades under the ticker MRK. The company is conducting clinical trials to evaluate the drug for various Gram-negative bacterial infections in both adult and pediatric populations.

What phase is Ceftolozane/Tazobactam in?

Ceftolozane/Tazobactam is in Phase 2 clinical development. While one Phase 3 trial has been completed, the drug's overall development stage is Phase 2, and it remains investigational. It is not FDA approved and is still undergoing clinical evaluation for its safety and efficacy.

What clinical trials is Ceftolozane/Tazobactam in?

Ceftolozane/Tazobactam has been studied in several completed trials, including NCT02070757 for ventilated nosocomial pneumonia, NCT03217136 for pediatric complicated intra-abdominal infection, NCT03230838 for pediatric complicated urinary tract infection, and NCT04223752 for pediatric nosocomial pneumonia. These trials enrolled a total of 726 participants.

Is Ceftolozane/Tazobactam the same as MK-7625A?

Yes, Ceftolozane/Tazobactam is also known as MK-7625A. Clinical trial titles reference MK-7625A, such as NCT03217136 and NCT03230838, which study the drug in pediatric patients with complicated intra-abdominal and urinary tract infections.