E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052596 |
E.1.2 | Term | Nosocomial pneumonia |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of ceftolozane/tazobactam for all participants |
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetics (PK) of multiple doses of ceftolozane/tazobactam for each age group and/or dose level
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Has a diagnosis of proven or suspected NP (including HABP or VABP), as determined by the investigator. Note: The diagnosis of NP does not require a pathogen to be isolated from a diagnostic test. 2. Is hospitalized and anticipated to receive a minimum of 8 days of concomitant SOC antibiotic therapy for proven or suspected NP. The concomitant SOC antibiotic therapy can have coverage for either gram positive and/or gram-negative respiratory pathogen(s). Note: Concomitant SOC antibiotics may be stopped before the 8-day minimum at the discretion of the investigator. Participants who discontinue or complete concomitant SOC antibiotic therapy in less than 8 days may also discontinue ceftolozane/tazobactam prior to the minimum duration of 8 days at the investigator’s discretion. However, participants are strongly encouraged to receive a minimum of 8 days of ceftolozane/tazobactam. Demographics: 3. Is male or female (not pregnant or nursing) from birth (defined as >32 weeks gestational age and ≥7 days postnatal) to <18 years of age inclusive, at the time of signing the informed consent/assent. Male Participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of study intervention: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause ) as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. Female Participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) OR - Is a WOCBP and using an acceptable contraceptive method or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 30 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. - A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 48 hours before the first dose of study intervention. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Informed Consent/Assent: 4. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study. Additional Categories: 5. Is able to comply with all study procedures and restrictions for the duration of the study.
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E.4 | Principal exclusion criteria |
Medical Conditions: 1. Has a documented history of any moderate or severe hypersensitivity (or allergic) reaction to any β-lactam antibacterial. Note: A history of a rash while on a β-lactam antibiotic does not automatically exclude a participant (eg, a participant with history of a mild rash followed by uneventful re-exposure may be considered for enrollment). 2. For Groups 1-4, 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. For Group 5, has CrCL <20 mL/min/1.73 m2 based on the revised Schwartz equation or requirement for peritoneal dialysis, hemodialysis, or hemofiltration. Prior/Concomitant Therapy 3. 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. Prior/Concurrent Clinical Study Experience 4. Participation in any clinical study of a therapeutic investigational product within 30 days prior to the first dose of ceftolozane/tazobactam. 5.Previous participation in any study of ceftolozane or ceftolozane/tazobactam. Diagnostic Assessments: Not applicable. Other Exclusions: 6. Has one or more of the following laboratory abnormalities in a specimen obtained at screening: • Absolute neutrophil count (ANC) <1000/mm3 • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 × the upper limit of normal (ULN) • Total bilirubin ≥2 × the ULN (if 7 to ≤28 days of age and breastfeeding, total bilirubin >10 mg/dL OR ≥2 × ULN). 7. 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, including any of the following: •human immunodeficiency virus (HIV) infection, with a known CD4 percentage of <15% in pediatric participants ≤5 years of age, or CD4 count of <200 cells/mm3 in pediatric participants >5 years of age •active hematological malignancy •recipient of solid organ or bone marrow transplants •currently on immunosuppressive therapy, including cancer chemotherapy currently on medications for prevention of transplant rejection •chronic administration of corticosteroids (defined as >40 mg of prednisone per day administered continuously for more than 14 days prior to the first dose of ceftolozane/tazobactam) 10. Is or has an immediate family member (eg, parent/legal guardian or sibling) who is investigational site or Sponsor staff directly involved with this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
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
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.Up to Day 31 2.Up to Day 31 3.Up to Day 31 4.Up to Day 31 5.Up to Day 14
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E.5.2 | Secondary end point(s) |
1.Plasma concentrations of ceftolozane 2.Plasma concentrations of tazobactam 3.Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma ceftolozane 4.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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Evaluate the safety, tolerability and the PK in pediatric participants |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Estonia |
Greece |
Russian Federation |
Spain |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |