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)

Peri-operative Prophylaxis Clinical Trial

Official title:

A Phase 1, Non-comparative, Open-label Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of Ceftolozane/Tazobactam in Pediatric Patients Receiving Standard of Care Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02725216
• Other study ID #: 7625A-010
• Secondary ID: CXA-PEDS-13-08
• Status: Recruiting
• Phase: Phase 1
• First received: March 28, 2016
• Last updated: April 13, 2016
• Start date: September 2014
• Est. completion date: November 2016

Study information

• Verified date: April 2016
• Source: Merck Sharp & Dohme Corp.
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of a single intravenous dose of ceftolozane/tazobactam in pediatric participants.

Ceftolozane/tazobactam is a novel antibacterial consisting of ceftolozane, a unique antipseudomonal cephalosporin, with tazobactam, a well-established β-lactamase inhibitor.

This is the first study investigating the use of ceftolozane/tazobactam in pediatric participants.

Description:

Screening assessments will occur within 48 hours of study drug administration (Day 1). Baseline assessments will be performed following eligibility verification based on screening assessments.

Participants will be monitored for safety 24 hours post study drug infusion. The site will contact the participant and/or parent (or appropriate legal representative) via telephone at Study Day 8 (± 2 days) for assessment of adverse events and concomitant medications and procedures.

In each age cohort, an interim analysis of PK and safety data will be conducted after 3 participants have received the initially proposed dose. The interim analysis will determine whether this initial dose was appropriate based on pre-defined criteria.

If data from the interim analysis demonstrates that the initially proposed dose meets the criteria above, enrollment will continue with the same dose administered to 3 additional participants. However, if the interim analysis demonstrates that a new optimized adjusted dose is required, the new adjusted dose will be administered to 3 new participants of the same age range. In subsequent cohorts, the initial dose is also subject to change based upon the results of the interim analysis in previous cohorts.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

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/1.73m2 at baseline

4. Group 5: CLCR = 50 ml/min/1.73m2 at baseline

5. Group 6: CLCR = 20 ml/min/1.73m2 at baseline

Key Exclusion Criteria:

1. Known allergy/hypersensitivity to any ß-lactam antibacterial

2. History of clinically significant renal, hepatic, or hemodynamic instability

3. Planned use of cardiopulmonary bypass or dialysis

4. Planned blood transfusion within 24 hours of study drug administration

5. Clinically significant abnormal laboratory test results not related to the underlying infection

6. Receipt of piperacillin/tazobactam within 24 hours of study drug administration

7. Likely to be at risk of hemodynamic disturbance following collection of the required PK blood samples

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infections
• Gram-Negative Bacterial Infections
• Infection
• Peri-operative Prophylaxis
• Proven or Suspected Gram-negative Bacterial Infection

Intervention

Drug:
• ceftolozane/tazobactam

Locations

Country	Name	City	State
United States	Call for Information (Investigational Site 0121)	Ann Arbor	Michigan
United States	Call for Information (Investigational Site 0112)	Aurora	Colorado
United States	Call for Information (Investigational Site 0111)	Baton Rouge	Louisiana
United States	Call for Information (Investigational Site 0122)	Boston	Massachusetts
United States	Call for Information (Investigational Site 0109)	Cleveland	Ohio
United States	Call for Information (Investigational Site 0120)	Detroit	Michigan
United States	Call for Information (Investigational Site 0101)	Kansas City	Missouri
United States	Call for Information (Investigational Site 0108)	Little Rock	Arkansas
United States	Call for Information (Investigational Site 0113)	Long Beach	California
United States	Call for Information (Investigational Site 0116)	Louisville	Kentucky
United States	Call for Information (Investigational Site 0115)	Omaha	Nebraska
United States	Call for Information (Investigational Site 0103)	Orange	California
United States	Call for Information (Investigational Site 0119)	Royal Oak	Michigan
United States	Call for Information (Investigational Site 0117)	San Diego	California
United States	Call for Information (Investigational Site 0110)	Shreveport	Louisiana
United States	Call for Information (Investigational Site 0104)	Toledo	Ohio
United States	Call for Information (Investigational Site 0118)	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of ceftolozane/tazobactam		Assessed up to 6 hours after the start of study drug administration.	No
Primary	Time to Cmax (Tmax) of ceftolozane/tazobactam		Assessed up to 6 hours after the start of study drug administration.	No
Primary	Concentration at last sampling point (Clast) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Primary	Time of last sampling point (Tlast) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Primary	Area under the plasma concentration-time curve from 0 to time of last sample collected (AUC0-tlast) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Primary	Area under the plasma concentration-time curve from 0 to infinity (AUC0-8) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Primary	Elimination half-life (t1/2) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Primary	Volume of distribution at steady state (Vss) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Primary	Plasma clearance (CL) of ceftolozane/tazobactam		Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.	No
Secondary	Number of participants with one or more Adverse Events		Participants will be followed from the time of study drug administration (study day 1) through the last study follow up (may occur up to study day 10).	Yes
Secondary	Number of participants who discontinued study due to an Adverse Event		Participants will be followed on the day of study drug administration (study day 1).	Yes