| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of complicated urinary tract infection (cUTI), including pyelonephritis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Complicated Urinary Tract Infection |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037606 |
| E.1.2 | Term | Pyelonephritis, unspecified |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10046576 |
| E.1.2 | Term | Urinary tract infection, site not specified |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 compared with that of meropenem |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of ceftolozane/tazobactam compared with that of meropenem with respect to clinical response at the End of Treatment (EOT) and Test of Cure (TOC) Visits
2. To evaluate the efficacy of ceftolozane/tazobactam compared with that of meropenem with respect to per-subject microbiological response at the EOT and TOC Visits |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have a legally acceptable representative who provides documented
informed consent/assent for the trial.
2.Be a male or female from birth (defined as >32 weeks gestational age and ≥7 days postnatal) to <18 years of age
3.Be able to comply with the protocol for the duration of the trial
4.Require IV antibacterial therapy for the treatment of cUTI
5.Have a pretreatment baseline urine culture specimen obtained within 48 hours before the start of administration of the first dose of study treatment and preferably prior to administration of any potentially therapeutic antibiotics. Specimen is to be obtained by suprapubic aspiration, clean intermittent urethral catheterization, indwelling urethral catheter, or midstream clean catch
6.Have pyuria, defined as follows: a)If ≥1 year of age: White blood cell (WBC) count >10 cells/μL in unspun urine or ≥10 cells/high power field in spun urine b)If <1 year of age: WBC count >5 cells/μL in unspun urine or ≥5 cells/high power field in spun urine
7.Have clinical signs and/or symptoms of cUTI (pyelonephritis or cLUTI) at the Screening Visit as described in the protocol
8.Meet one of the following categories: a)The subject is a male who is not of reproductive potential, defined as a male who has azoospermia (whether due to being prepubertal, having had a vasectomy, or an underlying medical condition) b)The subject is a female who is not of reproductive potential, defined as a female who either: (1) Has not undergone menarche; (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening, or (3) has a congenital or acquired condition that prevents childbearing
c)The subject is a female or a male of reproductive potential who agrees to avoid becoming pregnant or impregnating partner during screening, while receiving study treatment, and for at least 30 days after the last dose of study treatment by complying with one of the following: (1) Practice abstinencea from heterosexual activity OR (2) use (or have their partner use) acceptable contraception during heterosexual activity. Refer to the protocol for the acceptable methods of contraception
9.Meet the following criteria for a female subject who is of reproductive potential: a)The subject is not pregnant (as confirmed by serum pregnancy test at screening) and not planning to become pregnant within 30 days of the last day of study treatment administration b)The subject is nonlactating |
|
| E.4 | Principal exclusion criteria |
1.Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days prior to the first dose of study treatment in this current trial
2.Has previously participated in any trial of ceftolozane or ceftolozane/tazobactam or has enrolled previously in the current trial and been discontinued
3.Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that, in the opinion of the investigator, might expose the subject to increased risk by participating in the trial, confound the results of the trial, or interfere with the subject’s participation for the full duration of the trial
4.Has a history of any moderate or severe hypersensitivity (eg, anaphylaxis), allergic reaction, or other contraindication to any of the following: β-lactam antibiotics (eg, penicillins, cephalosporins and carbapenems), or β-lactamase inhibitors (eg, tazobactam, sulbactam, clavulanic acid, avibactam)
5.Has a history of a cUTI within the past 1 year prior to randomization that is caused by a pathogen known to be resistant to either IV study treatment
6.Has a concomitant infection at the time of randomization that requires nonstudy systemic antibacterial therapy in addition to IV study treatment or oral step -down therapy (medications with only gram-positive activity [eg, vancomycin, linezolid] are allowed)
7.Has received potentially therapeutic antibacterial therapy (eg, with gram negative activity), including bladder infusions with topical urinary antiseptics or antibacterial agents, for a duration of more than 24 hours during the 48 hours preceding the first dose of study treatment
8.Has any of the following: a)Intractable UTI or pyelonephritis infection at baseline that the Investigator anticipates would require more than 14 days of study treatment b)Confirmed fungal urinary tract infection at time of randomization with ≥103 fungal CFU/mL c)Permanent indwelling bladder catheter or instrumentation including nephrostomy d)Current urinary catheter that is not scheduled to be removed before the end of all study treatment (intermittent straight catheterization during the study treatment period is acceptable) e)Complete, permanent obstruction of the urinary tract f)Suspected or confirmed perinephric or intrarenal abscess g)Documented ileal loop reflux h) Suspected or confirmed prostatitis, urethritis, or epididymitis i)Trauma to pelvis/urinary tract
9.Has moderate or 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
10.Has one or more of the following laboratory abnormalities in a
specimen obtained at baseline: a)Absolute neutrophil count (ANC)
<1000/mm3 b)Aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) ≥3 × the upper limit of normal (ULN) c)Total
bilirubin ≥2 × ULN (if 7 to ≤28 days of age and breastfeeding, total
bilirubin >10 mg/dL OR ≥2 × ULN)
11.Has a seizure disorder or is anticipated to be treated with divalproex
sodium or valproic acid during the course of study treatment
12. Is receiving, or is expected to receive, any of the following
medications:
a) Immunosuppressive agents
b) Valproic acid or divalproex sodium
c) Probenecid
13.Has any rapidly progressing disease or immediately life-threatening
illness including acute hepatic failure, respiratory failure, or septic shock
14.Has an immunocompromising condition, including established AIDS, hematological malignancy, or bone marrow transplantation, or is
receiving immunosuppressive therapy including cancer chemotherapy,
medications for prevention of organ transplantation rejection, or chronic administration of systemic corticosteroids (defined as the systemic equivalent of ≥2 mg/kg total daily dose of prednisone for participants ≤ 20 kg, or >40 mg of prednisone per day for participants >20 kg, administered continuously for more than 14 days in the 30 days prior to the first dose of ceftolozane/tazobactam)
15.Has a history of malignancy ≤5 years prior to signing informed
consent, except for adequately treated basal cell or squamous cell skin
cancer or in situ cervical cancer
16.Planned receipt of suppressive/prophylactic antibiotics with gramnegative activity after completion of study treatment
17.Is or has an immediate family member (e.g., spouse, parent/legal
guardian, sibling or child) who is investigational site or Sponsor staff
directly involved with this trial |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Adverse events (AEs)
2. Clinical laboratory tests
3. Vital signs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Safety evaluation all study visits |
|
| E.5.2 | Secondary end point(s) |
1. Clinical success at the End of Treatment (EOT) and Test of Cure (TOC) Visits
2. Per-subject microbiological eradication at the EOT and TOC Visits
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| End of IV Treatment (EOIV), End of treatment (EOT), Test of cure (TOC) |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| 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) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| open label Oral step down therapy / Standard of Care |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| 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 |
| Greece |
| Hungary |
| Mexico |
| Poland |
| Romania |
| Russian Federation |
| South Africa |
| Turkey |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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