Safety and pharmacokinetics of ceftolozane/tazobactam in pediatric participants with nosocomial pneumonia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

26 Feb 2020 → 26 Sep 2024

Decision date (initial)

2023-04-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501110-56-00

EudraCT number

2018-004704-19

WHO UTN

U1111-1279-4959

ClinicalTrials.gov

NCT04223752

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety

To evaluate the safety and tolerability of ceftolozane/tazobactam for all participants

Secondary objectives 1

1. To evaluate the pharmacokinetics (PK) of multiple doses of ceftolozane/tazobactam for each age group and/or dose level

Conditions and MedDRA coding

Nosocomial infection, Pneumonia

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001142-PIP02-16

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Is hospitalized and anticipated to receive a minimum of 8 days of concomitant standard-of-care [SOC] antibiotic therapy for proven or suspected nosocomial pneumonia (NP)
2. 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
3. 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 9

1. Has a documented history of any moderate or severe hypersensitivity (or allergic) reaction to any β-lactam antibacterial
2. 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
3. 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
4. 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
5. Has participated in any clinical study of a therapeutic investigational product within 30 days prior to the first dose of ceftolozane/tazobactam
6. Has previous participation in any study of ceftolozane or ceftolozane/tazobactam
7. 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
8. Has any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure or septic shock
9. Has active immunosuppression

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Percentage of participants with any adverse events (AEs)
2. Percentage of participants with any serious AEs (SAEs)
3. Percentage of participants with any drug-related AEs
4. Percentage of participants with any drug-related SAEs
5. Percentage of participants with AEs leading to discontinuation of study intervention

Secondary endpoints 12

1. Plasma concentrations of ceftolozane
2. Plasma concentrations of tazobactam
3. Steady state plasma area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma ceftolozane
4. Steady state plasma area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma tazobactam
5. Maximum observed concentration during a dosage interval (Cmax) of plasma ceftolozane
6. Maximum observed concentration during a dosage interval (Cmax) of plasma tazobactam
7. Elimination half-life (t1/2) of plasma ceftolozane
8. Elimination half-life (t1/2) of plasma tazobactam
9. Volume of distribution (Vd) of plasma ceftolozane
10. Volume of distribution (Vd) of plasma tazobactam
11. Clearance (CL) of plasma ceftolozane
12. Clearance (CL) of plasma tazobactam

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Stephen Richard Holden

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Stephen Richard Holden

Third parties 3

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications