| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC) or pancreatic cancer |
| Carcinoma mammario triplo negativo (TNBC), tumore ovarico, tumore gastrico, tumore colorettale (CRC), glioblastoma (GBM), tumori delle vie biliari (BTC) o tumore al pancreas |
|
| E.1.1.1 | Medical condition in easily understood language |
| Triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC) or pancreatic cancer |
| Carcinoma mammario triplo negativo (TNBC), tumore ovarico, tumore gastrico, tumore colorettale (CRC), glioblastoma (GBM), tumori delle vie biliari (BTC) o tumore al pancreas |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10028997 |
| E.1.2 | Term | Neoplasm malignant |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
1. To evaluate objective response rate (ORR) of pembrolizumab (MK-3475) in combination with lenvatinib (MK-7902) per tumor cohort based on Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) by investigator assessments in initial cohorts and blinded independent central review (BICR) in cohorts that expand combining the initial and expansion cohorts (Cohorts A-F). In Cohort G, RECIST 1.1 by BICR will be utilized in all participants (for participants with glioblastoma [GBM], response will be assessed based on Response Assessment in Neuro-Oncology [RANO] criteria)
2. To assess safety and tolerability of treatment with pembrolizumab in combination with lenvatinib per tumor cohort assessed by the percentage of adverse events (AEs)
3. To assess safety and tolerability of treatment with lenvatinib monotherapy assessed by the proportion of AEs |
1. Valutare il tasso di risposta obiettiva (ORR) di pembrolizumab (MK-3475) in associazione a lenvatinib (MK-7902) per coorte tumorale in base ai criteri RECIST 1.1 mediante valutazioni degli sperimentatori nelle coorti iniziali e BICR in coorti che si espandono combinando le coorti iniziali e di espansione (Coorti A-F). Nella Coorte G, i criteri RECIST 1.1 mediante BICR saranno utilizzati in tutti i partecipanti (per i partecipanti con [GBM], la risposta sarà valutata in base ai criteri [RANO])
2. Valutare la sicurezza e la tollerabilità del trattamento con pembrolizumab in associazione a lenvatinib per coorte tumorale valutate in base alla percentuale di EA
3. Valutare la sicurezza e la tollerabilità del trattamento con lenvatinib in monoterapia valutate in base alla proporzione di AE |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS) of pembrolizumab in combination with lenvatinib per tumor cohort based on RECIST 1.1 (RANO for GBM) by investigator assessments in initial cohorts and BICR in cohorts that expand combining the initial and expansion cohorts (Cohorts A-F). In Cohort G, RECIST 1.1 by BICR will be utilized in all participants
2. To evaluate overall survival (OS) of pembrolizumab in combination with lenvatinib per tumor cohort
3. To evaluate ORR, DCR, DOR, PFS, and OS of lenvatinib monotherapy based on RECIST 1.1 by BICR
4. To characterize the population pharmacokinetics (PK) of lenvatinib when co-administered with pembrolizumab in participants per tumor cohort (Cohorts A-F only) |
1. Valutare il tasso di controllo della malattia (DCR), la durata della risposta (DOR) e la sopravvivenza libera da progressione (PFS) di pembrolizumab in associazione a lenvatinib per coorte tumorale sulla base dei criteri RECIST 1.1 (RANO per GBM) mediante valutazioni degli sperimentatori in coorti iniziali e BICR in coorti che si espandono combinando le coorti iniziali e di espansione (Coorti A-F). Nella Coorte G, i criteri RECIST 1.1 mediante BICR saranno utilizzati in tutti i partecipanti
2. Valutare la sopravvivenza globale (OS) di pembrolizumab in associazione a lenvatinib per coorte tumorale
3. Valutare ORR, DCR, DOR, PFS, e OS di lenvatinib in monoterapia in base ai criteri RECIST 1.1 mediante BICR
4. Caratterizzare la farmacocinetica (PK) di popolazione di lenvatinib quando somministrato in associazione a pembrolizumab nei partecipanti per coorte tumorale (solo Coorti A-F) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts:
Cohort A Triple-Negative Breast Cancer (TNBC)
Cohort B Ovarian Cancer
Cohort C Gastric Cancer
Cohort D Colorectal Cancer
Cohort E Glioblastoma (GBM)
Cohort F Biliary Tract Cancer (BTC) (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater)
Cohort G Pancreatic Cancer (ductal adenocarcinoma)
2. Participants must have fulfilled cohort-specific requirements regarding prior (line of therapy) treatments.
3. Participants must have progressed on or since the last treatment
4. Have measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
5. Have provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
6. Participants are at least 18 years of age; male or female for gastric cancer, GBM, TNBC, CRC, BTC, and pancreatic cancer cohorts; female only for ovarian cancer
7. Life expectancy of 12 weeks or more
8. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib:
a. 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
b. 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
- 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, 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 120 days post pembrolizumab or 30
days post lenvatinib, whichever occurs last.
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 24 hours before the first dose of study intervention
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
10. The participant (or legally acceptable representative if applicable) has provided documented informed consent/assent for the study
11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days prior to allocation/randomization
12. Have adequate organ function
Other cancer-specific inclusion criteria- please refer to the Protocol |
1. Avere un tumore solido istologicamente o citologicamente documentato, avanzato (metastatico e/o non resecabile), incurabile e per il quale la terapia sistemica standard precedente abbia fallito in una delle seguenti coorti:
Coorte A: Carcinoma mammario triplo negativo (TNBC)
Coorte B: Tumore ovarico
Coorte C: Tumore gastrico
Coorte D: Tumore colorettale
Coorte E: Glioblastoma (GBM)
Coorte F: Tumore delle vie biliari (BTC) (colangiocarcinoma intraepatico o extraepatico, tumore della cistifellea; è esclusa l’ampolla di Vater)
Coorte G: Tumore del pancreas (adenocarcinoma duttale)
2. Aver soddisfatto i requisiti specifici della coorte per quanto riguarda i trattamenti precedenti (linee di terapia).
3. Essere andati incontro a progressione rispetto all’ultimo trattamento.
4. Avere una malattia misurabile secondo i criteri RECIST 1.1 (RANO per la coorte GBM) come valutata dallo sperimentatore/dal servizio di radiologia del centro locale e confermata mediante BICR. Le lesioni situate in un’area precedentemente irradiata sono considerate misurabili se si evidenzia una progressione in tali lesioni.
5. Fornire campioni di tessuto tumorale valutabili per PD-L1 presenti in archivio o di nuova acquisizione di una lesione tumorale non irradiata in precedenza. I blocchetti di tessuto fissati in formalina e inclusi in paraffina (Formalin-Fixed, Paraffin Embedded, FFPE) sono preferibili rispetto ai vetrini. Le biopsie ottenute ex-novo sono preferibili rispetto al tessuto archiviato.
6. I partecipanti hanno almeno 18 anni; di sesso maschile o femminile per le coorti di tumore gastrico, GBM, TNBC, CRC, BTC e tuomore del pancreas; solo di sesso femminile per il tumore ovarico
7. Aspettativa di vita di almeno 12 settimane.
8. I pazienti di sesso maschile sono idonei a partecipare se acconsentono a quanto segue durante il periodo di trattamento sperimentale e per almeno 7 giorni dopo l’ultima dose di lenvatinib:
a. Non avere rapporti eterosessuali come stile di vita preferito e abituale (astinenza a lungo termine e persistente) e accettare di astenersi da tali rapporti.
O
b. Acconsentire a utilizzare un metodo contraccettivo, a meno che non sia confermata l’azoospermia (in seguito a vasectomia o secondaria a cause mediche) come specificato di seguito:
- Acconsentire a utilizzare un preservativo maschile e a far utilizzare alla partner un metodo contraccettivo aggiuntivo in caso di rapporti sessuali penetrativi vaginali con una donna in età fertile che non sia al momento incinta.
- 7 giorni dopo l’interruzione del trattamento con lenvatinib, se il partecipante sta assumendo soltanto pembrolizumab non sono necessarie misure contraccettive da parte dei pazienti di sesso maschile.
Si prega di fare riferimento al protocollo per i restanti criteri di inclusione. |
|
| E.4 | Principal exclusion criteria |
1. Has presence of gastrointestinal condition including malabsorption that might affect the absorption of lenvatinib.
2. Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. The participant can receive diuretic drugs as needed per the treating physician, outside of the above mentioned conditions. This exclusion applies to all cohorts except the ovarian cancer cohort.
3. Has radiographic evidence of major blood vessel invasion/infiltration.
4. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug.
5. Has significant cardiovascular impairment within 12 months of the first dose of study drug.
6. Has a history of arterial thromboembolism within 12 months of start of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
8. Serious nonhealing wound, ulcer or bone fracture.
9. Has had major surgery within 3 weeks prior to first dose of study interventions.
10. Has biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before first dose of study treatment.
11. Has pre-existing >=Grade 3 gastrointestinal (GI) or nongastrointestinal fistula.
12. Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
13. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to study treatment start.
14. Has recovered adequately from the toxicity and/or complications from the intervention if participant received major surgery prior to starting study treatment.
15. Has received prior radiotherapy within 2 weeks of start of study treatment.
16. Has received a live vaccine within 30 days prior to the first dose of study drug.
17. Has known intolerance to lenvatinib (and/or any of the excipients).
18. Has participated or is currently participating in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
19. Has urine protein >=1 g/24h. Participants with proteinuria >1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria.
20. Has prolongation of QTc interval (calculated using Fridericia's formula) to >480 ms.
21. Has left ventricular ejection fraction (LVEF) <55% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
22. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
23. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
24. Has tumors involving the brain stem.
25. Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.
26. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
27. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
28. Has an active infection requiring systemic therapy.
29. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
30. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
For remaining exclusion criteria refer to Protocol. |
1. Presenza di disturbi gastrointestinali, compreso il malassorbimento che potrebbe influenzare l’assorbimento di lenvatinib.
2. Attuale o precedente accumulo di liquido pleurico, ascitico o pericardico che necessita di drenaggio o di farmaci diuretici nelle 2 settimane precedenti l’arruolamento. Il partecipante può ricevere farmaci diuretici secondo necessità se prescritti dal medico curante, fatta eccezione per le condizioni sopraccitate. Questa esclusione si applica a tutte le coorti ad eccezione della coorte del tumore ovarico.
3. Presenta evidenze radiografiche di invasione/infiltrazione dei vasi sanguigni maggiori.
4. Ha avuto emottisi o emorragia tumorale clinicamente significative nelle 2 settimane precedenti la prima dose del trattamento in studio.
5. Ha avuto una significativa compromissione cardiovascolare nei 12 mesi precedenti la prima dose di farmaco sperimentale.
6. Ha un’anamnesi di tromboembolia arteriosa nei 12 mesi precedenti l’inizio della terapia con il farmaco sperimentale.
7. Presenta un ulteriore tumore maligno noto che è progredito o ha richiesto un trattamento attivo negli ultimi 3 anni.
8. Ferita grave non cicatrizzante, ulcera o frattura ossea.
9. Si è sottoposto a un intervento chirurgico maggiore nelle 3 settimane precedenti la prima dose del trattamento in studio.
10. Ha modificatori della risposta biologica (ad esempio, fattore di stimolazione le colonie di granulociti) nelle 4 settimane prima dell’ingresso nello studio. La terapia cronica con eritropoietina è consentita a condizione che non siano stati effettuati aggiustamenti di dose nei 2 mesi precedenti la prima dose del trattamento sperimentale.
11. Ha una fistola gastrointestinale (GI) o non gastrointestinale preesistente >=Grado 3.
12. Ha ricevuto una terapia precedente con lenvatinib, un agente anti-PD-1, anti-PD-L1 o anti-PD-L2 o un agente diretto contro un altro recettore delle cellule T co-inibitorio o stimolatorio (ad es. CTLA-4, OX-40, CD137).
13. Ha ricevuto precedente terapia antitumorale sistemica tra cui agenti sperimentali nelle 4 settimane precedenti l’inizio del trattamento sperimentale.
14. Si è ristabilito adeguatamente dalla tossicità e/o dalle complicanze dell’intervento se si è sottoposto a un intervento chirurgico maggiore prima di iniziare il trattamento sperimentale.
15. Ha ricevuto precedente radioterapia nelle 2 settimane precedenti l’inizio del trattamento sperimentale.
16. Vaccinazione con vaccino vivo nei 30 giorni precedenti la prima dose del trattamento in studio.
17. Intolleranza nota a lenvatinib (e/o a uno qualsiasi degli eccipienti).
18. Partecipazione attuale o precedente a uno studio su un agente sperimentale o utilizzo di un dispositivo sperimentale nelle 4 settimane precedenti la prima dose del trattamento sperimentale.
19. Ha proteine delle urine >=1 g/24 h. I partecipanti con proteinuria >1+ sull’analisi delle urine su striscia reattiva saranno sottoposti a raccolta di urine nelle 24 ore per la valutazione quantitativa della proteinuria.
20. Ha un prolungamento dell’intervallo QTc (calcolato con la formula di Fridericia) a >480 ms.
21. Ha una frazione di eiezione ventricolare sinistra (LVEF) <55% valutata mediante angiocardioscintigrafia o ecocardiogramma.
22. Ha una diagnosi di immunodeficienza o sta assumendo un trattamento cronico con steroidi sistemici (in dosi superiori a 10 mg/die di un equivalente del prednisone) o qualsiasi altra forma di terapia immunosoppressiva nei 7 giorni precedenti la prima dose di farmaco sperimentale.
23. Presenta metastasi al sistema nervoso centrale (SNC) attive note e/o meningite carcinomatosa.
24. Ha tumori che coinvolgono il tronco encefalico.
25. Ha ipersensibilità grave (grado >=3) a pembrolizumab e/o a uno qualsiasi degli eccipienti.
Per i restanti criteri di esclusione fare riferimento al Protocollo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) criteria for glioblastoma (GBM) by investigator assessment in initial cohorts
2. ORR per RECIST 1.1 or RANO by blinded independent central review (BICR) in expanded cohorts 3. Percentage of participants receiving pembrolizumab plus lenvatinib who experience an adverse event (AE)
4. Percentage of participants receiving pembrolizumab plus lenvatinib who discontinue study treatment due to an AE
5. Percentage of participants receiving lenvatinib monotherapy who experience an AE
6. Percentage of participants receiving lenvatinib monotherapy who discontinue study treatment due to an AE |
1. Tasso di risposta obiettiva (ORR) secondo i criteri RECIST 1.1 o RANO per la coorte GBM mediante valutazioni degli sperimentatori in coorti iniziali
2. ORR in base ai criteri RECIST 1.1 o RANO mediante BICR in coorti che si espandono
3. Percentuale di partecipanti che sta assumendo pembrolizumab più lenvatinib in cui si verifica un Evento Avverso (AE)
4. Percentuale di partecipanti che sta assumendo pembrolizumab più lenvatinib che discontinua il trattamento a causa di un Evento Avverso (AE)
5. Percentuale di partecipanti che sta assumendo lenvatinib in monoterapia in cui si verifica un Evento Avverso (AE)
6. Percentuale di partecipanti che sta assumendo lenvatinib in monoterapia che discontinua il trattamento a causa di un Evento Avverso (AE) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 72 months
2. Up to approximately 72 months
3. Up to approximately 72 months
4. Up to approximately 72 months
5. Up to approximately 72 months
6. Up to approximately 72 months |
1. Approssimativamente fino a 72 mesi
2. Approssimativamente fino a 72 mesi
3. Approssimativamente fino a 72 mesi
4. Approssimativamente fino a 72 mesi
5. Approssimativamente fino a 72 mesi
6. Approssimativamente fino a 72 mesi |
|
| E.5.2 | Secondary end point(s) |
1. Disease Control Rate (DCR) per RECIST 1.1 by investigator assessment in initial cohorts
2. Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by investigator assessment in initial cohorts
3. Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by investigator assessment in initial cohorts
4. Overall Survival (OS) in initial cohorts
5. DCR per RECIST 1.1 by BICR in expanded cohorts
6. DOR per RECIST 1.1 or RANO (GBM) by BICR in expanded cohorts
7. PFS per RECIST 1.1 or RANO (GBM) by BICR in expanded cohorts
8. OS in expanded cohorts
9. ORR per RECIST 1.1 by BICR in lenvatinib monotherapy arm
10. DCR per RECIST 1.1 by BICR in lenvatinib monotherapy arm
11. DOR per RECIST 1.1 by BICR in lenvatinib monotherapy arm
12. PFS per RECIST 1.1 by BICR in lenvatinib monotherapy arm
13. OS in lenvatinib monotherapy arm
14. Plasma concentration of lenvatinib; 1. Tasso di controllo della malattia (DCR) secondo i criteri RECIST 1.1 mediante valutazioni degli sperimentatori in coorti iniziali
2. Durata della risposta (DOR) secondo i criteri RECIST 1.1 o RANO (GBM) mediante valutazioni degli sperimentatori in coorti iniziali
3. Sopravvivenza libera da progressione (PFS) secondo i criteri RECIST 1.1 o RANO (GBM) mediante valutazioni degli sperimentatori in coorti iniziali
4. Sopravvivenza globale (OS) in coorti iniziali
5. DCR secondo i criteri RECIST 1.1 mediante BICR in coorti che si espandono
6. DOR secondo i criteri RECIST 1.1 o RANO (GBM) mediante BICR in coorti che si espandono
7. PFS secondo i criteri RECIST 1.1 o RANO (GBM) mediante BICR in coorti che si espandono
8. OS in coorti che si espandono
9. ORR secondo i criteri RECIST 1.1 mediante BICR nel braccio con lenvatinib in monoterapia
10. DCR secondo i criteri RECIST 1.1 mediante BICR nel braccio con lenvatinib in monoterapia
11. DOR secondo i criteri RECIST 1.1 mediante BICR nel braccio con lenvatinib in monoterapia
12. PFS secondo i criteri RECIST 1.1 mediante BICR nel braccio con lenvatinib in monoterapia
13. OS nel braccio con lenvatinib in monoterapia
14. Concentrazione plasmatica di lenvatinib |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 72 months
2. Up to approximately 72 months
3. Up to approximately 72 months
4. Up to approximately 72 months
5. Up to approximately 72 months
6. Up to approximately 72 months
7. Up to approximately 72 months
8. Up to approximately 72 months
9. Up to approximately 72 months
10. Up to approximately 72 months
11. Up to approximately 72 months
12. Up to approximately 72 months
13. Up to approximately 72 months
14. Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose. Each cycle is 21 days. |
1. Approssimativamente fino a 72 mesi
2. Approssimativamente fino a 72 mesi
3. Approssimativamente fino a 72 mesi
4. Approssimativamente fino a 72 mesi
5. Approssimativamente fino a 72 mesi
6. Approssimativamente fino a 72 mesi
7. Approssimativamente fino a 72 mesi
8. Approssimativamente fino a 72 mesi
9. Approssimativamente fino a 72 mesi
10. Approssimativamente fino a 72 mesi
11. Approssimativamente fino a 72 mesi
12. Approssimativamente fino a 72 mesi
13. Approssimativamente fino a 72 mesi
14. Ciclo 1 Giorno 1: 0.5-4 ore e 6-10 ore post-dose; Ciclo 1 Giorno 15: pre-dose e 2-12 ore post-dose; Ciclo 2 Giorno 1: pre-dose, 0.5-4 ore, e 6-10 ore post-dose. Ogni ciclo dura 21 giorni. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| 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.8.2.4 | 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 | 25 |
| 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 | Information not present in EudraCT |
| 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 |
| Australia |
| Canada |
| Chile |
| Colombia |
| Israel |
| Korea, Republic of |
| Russian Federation |
| Taiwan |
| Thailand |
| United States |
| France |
| Germany |
| Italy |
| Spain |
| Switzerland |
| United Kingdom |
| Argentina |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| 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 | 5 |
| 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 |
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