| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Complicated staphylococcus aureus bacteremia (cSAB) |
| Batteriemia sostenuta da Staphylococcus aureus, endocardite infettiva compresa |
|
| E.1.1.1 | Medical condition in easily understood language |
| Complicated staphylococcus aureus bacteremia (cSAB) |
| Infezione batterica |
|
| 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 | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058887 |
| E.1.2 | Term | Staphylococcus aureus bacteremia |
| 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 demonstrate the non-inferiority of ceftobiprole to daptomycin for overall success as assessed by an independent Data Review Committee (DRC) in the treatment of S. aureus bacteremia (SAB), including infective endocarditis (IE), at the post-treatment evaluation (PTE) visit in the modified intent-to-treat (mITT) population. |
| Dimostrare la non inferiorità di ceftobiprolo rispetto a daptomicina in termini di successo globale secondo quanto valutato da un comitato di revisione dei dati (DRC) indipendente nel trattamento della batteriemia sostenuta da S. aureus (SAB), inclusa l’endocardite infettiva (IE) , alla visita di valutazione post-trattamento (PTE) nella popolazione intent-to-treat modificata (mITT). |
|
| E.2.2 | Secondary objectives of the trial |
To compare ceftobiprole with daptomycin with respect to:
1. All-cause mortality through Day 70 (PTE visit) and Day 28 in the intent-to-treat (ITT) and mITT populations.
2. Microbiological eradication rates (negative blood culture for S. aureus) at Day 4, Day 8, and the end-of-treatment (EOT) and PTE visits.
3. Overall success rates in the mITT, ITT, and clinically evaluable (CE) populations:
a) at the EOT and PTE visits (ITT and CE populations only)
b) at the EOT and PTE visits, for IE vs non-IE SAB
c) at the EOT and PTE visits, by renal-function status
4. Development of new metastatic foci, or other complications of SAB, after Day 7.
5. Time-to-first-blood-culture-negative for S. aureus, confirmed by a second blood-culture-negative for S. aureus, obtained at least 24 h after the first negative blood-culture.
6. Safety and tolerability (Safety population).
To assess the pharmacokinetics (PK) of ceftobiprole. |
Confrontare ceftobiprolo con daptomicina in termini di:
1. Mortalità per ogni causa fino al Giorno 70 (visita PTE) e al Giorno 28 nelle popolazioni intent-to-treat (ITT) e mITT.
2. Tassi di eradicazione microbiologica (emocoltura negativa per S. aureus) al Giorno 4, al Giorno 8 e alle visite di fine trattamento (EOT) e PTE.
3. Tassi di successo globale nelle popolazioni mITT, ITT e clinicamente valutabile (CE):
a) alle visite EOT e PTE (solo popolazioni ITT e CE);
b) alle visite EOT e PTE per SAB IE versus non IE;
c) alle visite EOT e PTE in funzione dello stato di funzionalità renale.
4. Sviluppo di nuovi focolai metastatici o altre complicanze della SAB dopo il Giorno 7.
5. Tempo alla prima emocoltura negativa per S. aureus confermata da una seconda emocoltura negativa per S. aureus ottenuta almeno 24 ore dopo la prima.
6. Sicurezza e tollerabilità (popolazione di sicurezza).
7. Valutare la farmacocinetica (PK) di ceftobiprolo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female ≥ 18 years of age.
2. Informed consent signed by the patient (or by their legally acceptable representative, if appropriate) indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study.
3. SAB, based on at least one S. aureus-positive blood culture obtained within the 72 h prior to randomization:
(a) identified by culture laboratory report, or
(b) positive diagnostic test for S. aureus (e.g., polymerase chain reaction [PCR], tube coagulase test and fluorescent in situ hybridization[FISH]) obtained from a blood culture.
Note: The microbiological work-up of the blood culture may:
Occur prior to informed consent to participation in the study
Be undertaken either on-site or in an external microbiology laboratory specifically appointed for the purposes of this study.
Use a diagnostic test:
– routinely performed locally for the detection of S. aureus from blood cultures
or
– provided to the laboratory for the purpose of this study, if the test has regulatory approval in the country where the test is being performed.
Nevertheless, patients without a Central Microbiology Laboratory assessment may be included in the mITT population if there is unequivocal documented evidence of a baseline blood culture positive for S. aureus at the local laboratory
4. At least two of the following signs or symptoms of bacteremia within the 72 h prior to randomization:
(a) fever > 38°C/100.4°F measured orally, > 38.5 °C / 101.3 °F measured tympanically, > 37.5° C / 99.5 °F measured by axillary method, or > 39 °C / 102.2 °F measured rectally
(b) white blood cell (WBC) count > 10.0 × 109/L, or < 4.0 × 109/L, or > 10% immature neutrophils (bands)
(c) tachycardia (heart rate > 90 bpm)
(d) hypotension (systolic blood pressure < 90 mmHg)
5. Required duration of study antibacterial treatment ≤ 28 days.
6. SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis.
7. Persistent SAB: documented failure of bloodstream clearance, defined as a positive blood culture for S. aureus within the 72 h prior to randomization, after prior appropriate anti-staphylococcal treatment (except failure under daptomycin therapy) of at least 3 complete days.
8. Other forms of complicated SAB, including the following:
(a) Acute bacterial skin or skin-structure infections (ABSSSIs)
(b) Metastatic infection of native tissue requiring ≤ 28 days of study antibacterial treatment.
Examples include but are not limited to:
Septic arthritis or bacterial joint infection/empyema
Septic or suppurative thrombophlebitis
Visceral soft-tissue abscesses requiring ≤ 28 days of study antibacterial treatment
Septic pulmonary emboli/infarction
Note: The diagnosis of a septic pulmonary embolism will be made by the investigator based on clinical symptoms of fever, cough, putum/hemoptysis in the presence of an extrapulmonary infection, sepsis, or risk factors for septic emboli (e.g., intravenous drug use) and will be based on the following radiological signs:
Contrast-enhanced CT (preferred):
Peripheral and/or subpleural multifocal nodular lesions (in different stages of cavitation) or wedgeshaped infiltrates
– with/without a feeding vessel sign (vessel leading to the nodule)
– with/without pleural effusion or features suggestive of pleural empyema
Non-contrast enhanced CT (e.g., in patients with a contraindication for contrast administration):
Peripheral and/or subpleural multifocal nodular lesions (in different stages of cavitation) or wedgeshaped infiltrates
– with/without pleural effusion or features suggestive of pleural empyema
Plain X-ray (e.g., in patients unable to undergo a CT):
Multifocal nodular densities or wedge-shaped infiltrates in varying stages of cavitation with or without pleural effusion or features suggestive of pleural empyema
9. Definite native-valve right-sided IE (RIE) by Modified Duke’s Criteria if both of the following
conditions are met:
(a) Absence of clinical and/or radiological evidence of cerebral foci
(b) Absence of other complications requiring more than 28 days of antibacterial Treatment
For more Information on inclusion criteria 9, please check the protocol. |
1. Uomo o donna di età ≥ 18 anni.
2. Sottoscrizione del consenso informato da parte del paziente (o del suo rappresentante legale, se pertinente), indicante che il soggetto comprende le finalità e le procedure richieste dallo studio ed è disposto a prendervi parte.
3. SAB, in base ad almeno un’emocoltura positiva per S. aureus effettuata nelle 72 ore precedenti la randomizzazione:
(a) identificata mediante referto di laboratorio dell’esame colturale o
(b) test diagnostico positivo per S. aureus (per es. reazione a catena della polimerasi [PCR], test della coagulasi con metodo in provetta e ibridazione in situ fluorescente [FISH]) su un’emocoltura.
N.B.: il work-up microbiologico dell’emocoltura potrà:
• Avere luogo prima del rilascio del consenso informato alla partecipazione allo studio (vedere paragrafo 5.2.1 e Tabella 7).
• Essere effettuato in loco o da un laboratorio microbiologico esterno specificatamente incaricato ai fini dello studio.
• Avvalersi di un test diagnostico:
– eseguito di routine a livello locale per la ricerca di S. aureus da emocolture o
– fornito al laboratorio ai fini dello studio, laddove il test sia stato approvato dall’autorità regolatoria nel paese in cui viene condotto.
Indipendentemente dal metodo diagnostico, sarà opportuno adoperarsi per isolare e trasmettere al laboratorio microbiologico centrale tutti gli organismi identificati nel sangue in modo univoco; ciò vale soprattutto per S. aureus isolato nel sangue alla visita di Screening. Il laboratorio microbiologico centrale identificherà nuovamente tutti gli organismi isolati. I risultati verranno usati per determinare se il paziente soddisfi i criteri di inclusione dello studio.
I pazienti senza valutazione del laboratorio microbiologico centrale potranno essere comunque inclusi nella popolazione mITT in presenza di evidenze inequivocabili documentate di un’emocoltura basale positiva per S. aureus presso il laboratorio locale.
4. Almeno due dei seguenti segni o sintomi di batteriemia nelle 72 ore precedenti la randomizzazione:
(a) febbre > 38°C rilevata mediante misurazione orale, > 38,5°C rilevata mediante misurazione timpanica, > 37,5°C rilevata mediante misurazione ascellare o > 39°C rilevata mediante misurazione rettale;
(b) conta dei globuli bianchi (WBC) > 10,0 × 109/l o < 4,0 × 109/l o > 10% di neutrofili immaturi (bande);
(c) tachicardia (frequenza cardiaca > 90 bpm);
(d) ipotensione (pressione sistolica < 90 mmHg).
5. Durata necessaria del trattamento antibatterico in studio ≤ 28 giorni.
6. SAB in pazienti sottoposti a emodialisi intermittente cronica o dialisi peritoneale.
7. SAB persistente: fallimento documentato della clearance dal torrente circolatorio, intesa come un’emocoltura positiva per S. aureus nelle 72 ore precedenti la randomizzazione dopo un precedente trattamento antistafilococcico adeguato (fatta eccezione per il fallimento con terapia a base di daptomicina) della durata di almeno 3 giorni completi.
8. 8. Altre forme di SAB complicata, compreso quanto segue:
(a) Infezioni batteriche acute della cute e della struttura cutanea (ABSSSI).
(b) Infezione metastatica del tessuto nativo che necessita di ≤ 28 giorni di trattamento con il farmaco antibatterico in studio, tra cui, per esempio:
• Artrite settica o infezione/empiema batterico dell’articolazione
• Tromboflebite settica o suppurativa.
• Ascessi viscerali dei tessuti molli che necessitano di ≤ 28 giorni di trattamento con il farmaco antibatterico in studio.
• Infarto/emboli settici polmonari.
N.B.: la diagnosi di embolia settica polmonare verrà formulata dallo sperimentatore in base a sintomi clinici di febbre, tosse, espettorato/emottisi in presenza di infezione extrapolmonare, sepsi o fattori di rischio per emboli settici (per es. uso di farmaci per via endovenosa) e sarà fondata sui seguenti segni radiologici:
Tomografia computerizzata (TC) con mezzo di contrasto (preferibilmente):
Lesioni nodulari multifocali periferiche e/o subpleuriche (a diversi stadi di cavitazione) o infiltrati cuneiformi
– con/senza segno del vaso afferente (vaso che conduce al nodulo);
– con/senza versamento pleurico o caratteristiche indicanti empiema pleurico.
TC senza mezzo di contrasto (per es. nei pazienti con controindicazione alla somministrazione del mezzo di contrasto):
Lesioni nodulari multifocali periferiche e/o subpleuriche (a diversi stadi di cavitazione) o infiltrati cuneiformi
– con/senza versamento pleurico o caratteristiche indicanti empiema pleurico.
Radiografia semplice (per es. nei pazienti non in grado di sottoporsi a una TC):
Densità nodulari multifocali o infiltrati cuneiformi a diversi stadi di cavitazione, con o senza versamento pleurico o caratteristiche indicanti empiema pleurico.
|
|
| E.4 | Principal exclusion criteria |
1. Treatment with potentially effective (anti-staphylococcal) systemic antibacterial treatment for more than 48 h within the 7 days prior to randomization.
2. Bloodstream or non-bloodstream concomitant infections with Gram-negative bacteria that are known (at Screening) to be non-susceptible to either ceftobiprole or aztreonam.
3. Confirmed uncomplicated SAB (e.g., catheter-related non-persistent SAB without signs of SAB complications, unless the patient has end-stage renal disease and is on intermittent hemodialysis or peritoneal dialysis).
4. Left sided infective endocarditis (known or suspected to be present at the time of randomization).
Note: If LIE is diagnosed after commencement of study therapy, the patient must be discontinued from the study and switched to non-study standard-of-care antibacterial treatment, and will be maintained in the mITT population and considered a failure.
5. Prosthetic cardiac valves or valve support rings, cardiac pacemakers, automatic implantable cardioverter-defibrillator, or left-ventricular assist devices.
6. Complicated SAB in patients with other foreign body material that cannot be removed within the 7 days after randomization.
Exceptions:
Patients with non-infected coronary stents may be included regardless of the time of stent implantation.
Patients with non-infected (no signs or symptoms of clinical involvement at the time of randomization) prosthetic joints, plates, spinal hardware, or other extravascular material may be included if implantation of the foreign material was performed at least 60 days before randomization.
Patients with non-infected (no signs or symptoms of clinical involvement at the time of randomization) intravascular prosthetic material or vena cava filters may be included if implantation of the foreign material was performed at least 90 days before randomization
|
I pazienti che soddisferanno uno qualsiasi dei seguenti criteri di esclusione allo Screening non potranno accedere allo studio:
1. Trattamento con una terapia antibatterica sistemica (antistafilococcica) potenzialmente efficace per oltre 48 ore nei 7 giorni precedenti la randomizzazione (vedere Appendice 5).
Eccezione: fallimento documentato della clearance del torrente circolatorio con un precedente trattamento antistafilococcico (fatta eccezione per il fallimento con terapia a base di daptomicina) somministrato per almeno 3 giorni completi.
2. Infezioni concomitanti del torrente circolatorio o di altra natura sostenute da batteri Gram-negativi notoriamente (allo Screening) non sensibili a ceftobiprolo o aztreonam.
3. SAB non complicata confermata (per es. SAB non persistente correlata all’uso del catetere senza segni di complicanze della SAB, salvo laddove il paziente sia affetto da malattia renale in stadio terminale e sia sottoposto a emodialisi intermittente o dialisi peritoneale).
4. Endocardite infettiva del cuore sinistro (nota o sospetta al momento della randomizzazione). N.B.: qualora la LIE venga diagnosticata dopo l’inizio della terapia in studio, il paziente dovrà essere estromesso dalla sperimentazione e dovrà passare a un trattamento antibatterico standard diverso da quello in studio. Il paziente rimarrà parte integrante della popolazione mITT e verrà considerato un fallimento.
5. Valvole cardiache protesiche o anelli valvolari, pacemaker cardiaci, defibrillatore automatico impiantabile o dispositivi di assistenza ventricolare sinistra.
6. SAB complicata in pazienti con altri materiali estranei all’interno dell’organismo non rimovibili entro 7 giorni successivi alla randomizzazione.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Overall success at the PTE visit (Day 70±5 days post-randomization) in the mITT analysis set, as assessed by the DRC.
The primary endpoint will be tested for the non-inferiority of ceftobiprole versus daptomycin using a non-inferiority margin of 15%.
Overall success is defined as all of the following criteria being met:
1. Patient alive at Day 70 (±5 days) post-randomization.
2. No new metastatic foci or complications of the SAB infection.
3. Resolution or improvement of SAB-related clinical signs and symptoms.
4. Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus):
at least one while the patient is on active study treatment; AND
confirmed by at least one subsequent negative blood culture for S. aureus,
- either in the period between 7 days after the EOT visit and the PTE visit
-or at the PTE visit
Treatment failure is defined as any of the following:
1. Premature discontinuation of study treatment due to DRC-assessed lack of efficacy (as assessed by the DRC) or for adverse events (AEs) that represent manifestation of disease progression or relapse, at any time between first dose of study drug and the PTE visit.
2. Development of new metastatic or other complications related to SAB between Day 8 and the PTE visit. Development of new metastatic or other complications of SAB prior to Day 8 will be assessed by the DRC on a case-by-case basis to assess whether These constitute a delayed manifestation of the baseline disease or new complications.
3. SAB relapse or reinfection based on evidence from a blood culture positive for S. aureus (after documented clearance of S. aureus from the bloodstream and clinical improvement) between the EOT and PTE visits.
4. Receipt of systemic non-study antibacterial treatment, other than those permitted under the protocol, for the treatment of SAB. This includes patients who are prematurely discontinued from study therapy due to an AE, but who require continuation of antibacterial treatment for SAB.
5. Treatment of infections other than SAB with systemic non-study antibacterial treatment which is potentially effective against S. aureus , and which is considered by the DRC to have a relevant impact on the primary endpoint
6. Death for any reason between first administration of study drug and the PTE visit.
7. Indeterminate outcome, defined as any data needed to determine whether the outcome is success or failure missing at the PTE visit, including but not limited to:
a) missing PTE visit, or missing key data to evaluate the primary endpoint
b) lost-to-follow-up, or patients who withdrew consent prior to the PTE visit
c) patients not meeting the criteria for Success or Failure, or patients not meeting all criteria for overall success
8. Requirement for systemic antibacterial treatment for SAB beyond 28 days. |
Successo globale alla visita PTE (Giorno 70±5 giorni post-randomizzazione) nel set di analisi mITT, secondo quanto valutato dal DRC (vedere Appendice 4). Il DRC consisterà in un gruppo di esperti clinici indipendenti, non al corrente del trattamento assegnato e non associati alla conduzione dello studio. Tali esperti esamineranno i profili dei pazienti, compresi segni e sintomi di infezione, ed eventuali risultati microbiologici e di imaging di rilievo, valutando inoltre gli outcome clinici e microbiologici dei pazienti. L’endpoint primario verrà testato per la non inferiorità di ceftobiprolo rispetto a daptomicina con un margine di non inferiorità del 15%.Con successo globale si intende il soddisfacimento di tutti i criteri che seguono:
1. Pazienti in vita al Giorno 70 (±5 giorni) post-randomizzazione.
2. Assenza di nuovi focolai metastatici o complicanze dell’infezione SAB.
3. Risoluzione o miglioramento di segni e sintomi clinici correlati alla SAB.
4. Due emocolture negative per S. aureus (senza successive emocolture positive per S. aureus):
• almeno una mentre il paziente è sottoposto al trattamento in studio attivo, E
• confermate da almeno una successiva emocoltura negativa per S. aureus
nel periodo compreso tra i 7 giorni dopo la visita EOT e la visita PTE o alla visita PTE
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Day 70 (±5 days) post-randomization, day 8, beyond 28 days |
| : giorno 70 (±5 giorni) giorno 8 , più di 28 giorni |
|
| E.5.2 | Secondary end point(s) |
1. All-cause mortality (mITT population) at Day 70 (PTE visit)
All-cause mortality will also be assessed at Day 28, and in the ITT population, and will be assessed descriptively.
2. Microbiological eradication (mITT population) at Day 70 (PTE visit)
Microbiological eradication will also be assessed in the CE population, and at Day 4, Day 8, and the EOT visit, and will be assessed descriptively.
Eradication: No growth of the baseline pathogen(s) , secondary to an adequate clinical response , based on a negative blood culture while the patient is on active study treatment which is confirmed by at least one subsequent negative blood culture for S. aureus, either in the period between 7 days after EOT and the PTE visit, or at the PTE visit.
Failure: Persistence relapse, or reinfection of S. aureus infection, defined as one or more of:
Ongoing positive blood cultures leading to discontinuation of the study drug
Subsequent isolation of S. aureus from a blood culture after clearance of bacteremia and clinical improvement,
Relapse: bloodstream infection with the same pathogen isolated at baseline based on genotyping
Reinfection: bloodstream infection with a different S. aureus strain to that isolated at baseline based on genotyping
Absence of at least two negative blood cultures (at least one negative blood culture on active study treatment, and at least one post-treatment) to confirm eradication.
Relapse or reinfection between EOT and PTE that is reported to the investigator from a healthcare provider not involved in the study (e.g., from another hospital), needs to be thoroughly documented and will be reviewed by the investigator and the DRC for determination.
3. Overall success rate at PTE (CE population)
The overall success rate will also be assessed at the EOT visit in the mITT, ITT and CE populations, and in the ITT population at the PTE visit, and will be assessed descriptively.
4. Development of new metastatic foci or other complications of SAB after Day 7 (mITT population)
Development of new metastatic foci or other complications of SAB after Day 7 will also be assessed in the CE population, and will be assessed descriptively.
Timepoints: Day 8–EOT, and PTE
Newly diagnosed IE or complicated SAB with metastatic foci or other complications of S. aureus infection, including metastatic foci in the vertebral column (vertebral abscess, osteomyelitis, discitis or epidural abscess), cerebral abscess/infarction, splenic abscess/infarction, renal abscess/infarction, psoas abscess or other deep-tissue abscess, other metastatic infection of native tissue, septic Arthritis (or bacterial joint infection/empyema), septic or suppurative thrombophlebitis and septic pulmonary emboli/infarction.
5. Time to S. aureus bloodstream clearance (mITT and CE populations)
Timepoints: Day 3–EOT
Time-to-first-blood-culture-negative for S. aureus, confirmed by a second blood-culture-negative for S. aureus obtained at least 24 h after the first negative blood-culture.
6. Safety/Tolerability (Safety population)
Timepoints: First dose of study drug–PTE
Incidence, type, severity, and relationship to study medication of AEs; and changes in laboratory tests (hematology, biochemistry including haptoglobin, urinalysis, and Coombs-test).
7. Pharmacokinetics of ceftobiprole (PK population)
Plasma levels of ceftobiprole and the beta-lactam ring-open product BAL1029
Sparse PK sampling (all patients)
Day 3: predose, 2 h (end of infusion), 4 to 6 h
Day 12: predose, 2 h (end of infusion), 4 to 6 h
Rich PK sampling (selected sites, N=40 patients)
Day 3: predose, 2 h (end of infusion), 3 h, 4 h, 6 h
Day 12: predose, 2 h (end of infusion), 4 to 6 h
Plasma-concentration data will be analyzed at each time point and will be presented as individual concentrations with descriptive statistics (mean, SD, CV%, min, median, max). |
Mortalità per ogni causa (popolazione mITT) al Giorno 70 (visita PTE)
Eradicazione microbiologica (popolazione mITT) al Giorno 70 (visita PTE
L’eradicazione microbiologica verrà a sua volta valutata in modo descrittivo nella popolazione CE il Giorno 4, il Giorno 8 e alla visita EOT
Tasso di successo globale alla PTE (popolazione CE) alla visita EOT
Sviluppo di nuovi focolai metastatici o altre complicanze della SAB dopo il Giorno 7 (popolazione mITT)
Tempo alla clearance di S. aureus dal torrente circolatorio (popolazioni mITT e CE) al giorno 3 e EOT
Sicurezza/tollerabilità (popolazione di sicurezza) alla somministrazione della prima dose del farmaco
Farmacocinetica di ceftobiprolo (popolazione PK) al giorno 3 e al giono 12
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Day 3, Day 4, Day 7, Day 8, Day 12, Day 28, Day 70, Day 3-EOT, EOT |
| giorno 3, giorno 4, giorno 7, giorno 8, giorno 12, giorno 28, giorno 70, giorno 3- fine del trattamento, fine del trattamento |
|
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 |
| Brazil |
| Bulgaria |
| Estonia |
| Georgia |
| Germany |
| Hungary |
| Israel |
| Italy |
| Mexico |
| Russian Federation |
| South Africa |
| Spain |
| 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
|
| The End of Study is defined as the completion of the last study-related contact with any patient, referred to as the date of ‘Last Patient, Last Visit’ (LPLV). |
| per conclusione della sperimentazione si intende l'ultima visita dell'ultimo paziente "LVLS" |
|
| 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 | 5 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
