E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated Urinary Tract Infection (cUTI)
Acute Pyelonephritis (AP) |
|
E.1.1.1 | Medical condition in easily understood language |
Complicated Urinary Tract Infection (cUTI)
Acute Pyelonephritis (AP) |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054088 |
E.1.2 | Term | Urinary tract infection bacterial |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 |
The primary objective of this study is to demonstrate the non-inferiority of plazomicin compared with meropenem based on the difference in composite microbiological eradication and clinical cure rate at both the Day 5 and test-of-cure (TOC) visits |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to:
- Summarize the composite microbiological eradication and clinical cure rates of plazomicin compared with meropenem at the Day 5 and TOC visits
- Evaluate the safety of plazomicin in patients with cUTI including AP
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Pyuria
- Have a pretreatment baseline urine culture obtained within 36 hours before the start of administration of the first dose of study drug
- Clinical signs and/or symptoms of acute pyelonephritis or complicated urinary tract infection
- Normal renal function or moderate renal impairment (calculated creatinine clearance (CLcr) at screening > 30 mL/min as estimated by the Cockcroft-Gault formula). |
|
E.4 | Principal exclusion criteria |
- Confirmed fungal urinary tract infection at the time of randomization
- Known urinary tract infection or colonization with Gram-positive pathogens
- Current cUTI or AP is known to be caused by a pathogen resistant to meropenem
- Female patients of childbearing potential if they are known to be pregnant or have a positive pregnancy test at screening, breastfeeding, or unable or unwilling to use a highly effective method of birth control during the study and for at least 30 days following the last dose of study medication
- Any rapidly progressing disease or immediately life-threatening illness
- Documented presence of immunodeficiency or an immunocompromised condition
- Documented or known history of otologic surgery or disease including use of hearing aid, head injury leading to otologic damage, Ménière's disease, tumor of the head, neck, or auditory system, perilymphatic fistula, or autoimmune disease of the inner ear, or family history of hearing loss (excluding age-related hearing loss [onset after age of 65 years]) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Composite microbiological eradication and clinical cure rate in the microbiological modified intent-to-treat population |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Days 5 and 17 (+/- 2 days) after study drug start |
|
E.5.2 | Secondary end point(s) |
(1) Composite microbiological eradication and clinical cure rate in the microbiologically evaluable population
(2) Overall incidence of adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1) Days 5 and 17 (+/- 2 days) after study drug start
(2) 32 Days |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 |
Argentina |
Brazil |
Bulgaria |
Chile |
Colombia |
Czech Republic |
Estonia |
Georgia |
Germany |
Hungary |
Latvia |
Mexico |
Poland |
Romania |
Russian Federation |
Serbia |
Spain |
Ukraine |
United Kingdom |
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 | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 23 |