| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Persistent Asthma |
| Trajna astma |
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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] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| 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 evaluate the efficacy of beclomethasone dipropionate administered via BAI and MDI (80 or 160 mcg/day) compared with placebo treatment in pediatric patients 4 through 11 years of age with persistent asthma as assessed by the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) percent predicted forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 12 weeks (FEV1 AUEC 0-12wk). |
| Primarni: utvrđivanje učinkovitosti beklometazon dipropionata primjenjivanog putem dahom aktiviranog inhalatora ili inhalatora s mjerenim dozama (80 ili 160 mcg/dan) u usporedbi s placebom u ispitanika pedijatrijske dobi između 4 i 11 godina s trajnom astmom putem procjene standardiziranog, prema početnoj vrijednosti prilagođenog najnižeg jutarnjeg (prije davanja doze i prije uzimanja bronhodilatatora za trenutačnu pomoć) postotka predviđene površine ispod krivulje učinka vrijednosti forsiranog ekspiratornog volumena u 1 sekundi (FEV1) od trenutka 0 do 12. tjedna (FEV1 AUEC0-12wk). |
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| E.2.2 | Secondary objectives of the trial |
1) to evaluate the efficacy of beclomethasone dipropionate treatment administered via BAI and MDI compared with placebo treatment in patients with persistent asthma
2) to evaluate the safety and tolerability of beclomethasone dipropionate treatment as assessed by the occurrence of treatment-emergent adverse events and vital signs assessments throughout the study; physical examination findings at the screening visit (SV) and the final treatment visit/treatment discontinuation visit (TV4/TdV); and oropharyngeal examination findings at every visit through TV4 |
1) utvrditi učinkovitost liječenja beklometazon dipropionatom primjenjivanog dahom aktiviranim inhalatorom i inhalatorom s mjerenim dozama u usporedbi s placebom u ispitanika s trajnom astmom
2) utvrditi sigurnost i podnošljivost liječenja beklometazon dipropionatom prema pojavi štetnih događaja proizašlih iz liječenja i mjerenjem vitalnih znakova tijekom ispitivanja, nalazima fizikalnih pregleda na posjetu za probir i na zadnjem posjetu za liječenje ili posjetu za prekid liječenja i nalazima orofaringealnog pregleda na svakom posjetu do zadnjeg posjeta za liječenje. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
a1. Severity of disease: The patient has persistent asthma, with a forced expiratory volume in 1 second (FEV1) 40% to 90% of the value predicted for age, height, and sex at screening visit (SV).
b1. Current asthma therapy: The patient is currently being treated with 1 of the following:
- a stable daily dosage of an inhaled corticosteroid (ICS) in the range of 88-176 mcg/day of fluticasone propionate (or equivalent) for a minimum of 4 weeks (28 days) before SV
- a stable daily dosage of non-corticosteroid therapy, including leukotriene modifiers, theophylline, chromones, or short-acting β2-agonists [SABAs] alone or in combination for a minimum of 4 weeks (28 days) before SV. Patients taking non-corticosteroid therapy will also need to meet uncontrolled asthma criteria before randomization
- a daily dose of ICS plus a LABA (at a dose less than or equivalent to fluticasone propionate 100 mcg/salmeterol 50 mcg twice daily) may be allowed but the patient will be required to discontinue this therapy and start fluticasone propionate MDI (44 mcg, 2 inhalations twice daily, for a total daily dose of 176 mcg/day or equivalent for at least 7 days to no more than 30 days before SV
c2. Reversibility of disease: The patient has demonstrated at least 12% reversibility of FEV1 within 30 minutes after 2-4 inhalations of albuterol/salbutamol hydrofluoroalkane (HFA) MDI (90 mcg ex-actuator) or equivalent at SV or on retesting. Patients aged 4-5 years who fail reversibility of FEV1 must demonstrate at least 12% reversibility of PEF after 2-4 inhalations of albuterol/salbutamol HFA MDI (90 mcg ex-actuator) or equivalent using the handheld peak flow meter. Nebulized albuterol/salbutamol at a total dose of 2.5 mg may be used at the investigator’s discretion. Reversibility values of 11.50-11.99 will be rounded to 12. A documented historical reversibility, including expiratory flow loops, of at least 12% to a beta-agonist in the previous 12 months before SV is acceptable for patients treated with ICS at baseline. Historical data is not acceptable for patients on non-corticosteroid therapy.
d. Written informed consent must be signed and dated by parent/legal guardian and the written informed assent form must be signed and dated by the patient (as applicable, per local regulations) before any study-related procedures are conducted.
e1. The patient is a male or female patient 4 through 11 years of age, inclusive, when informed consent/assent is signed (screening or prescreening visit, as applicable).
f. Asthma diagnosis: The patient has a diagnosis of asthma as defined by the NIH. The asthma diagnosis has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in medication) for at least 30 days before SV.
g1. The patient is able to perform acceptable and repeatable spirometry consistent with the ATS/ERS 2005 criteria
h. The patient is able to perform peak expiratory flow (PEF) (with assistance from parents/guardians/caregivers, as needed) with a hand-held peak flow meter.
i. The patient is able to use (with assistance from parents/guardians/caregivers, as needed) an MDI device without a spacer device and a BAI device.
j. The patient is able to withhold (as judged by the investigator) his or her morning regimen of asthma medication (non-corticosteroid therapy, ICS, or study drug) and rescue medication (eg, albuterol/salbutamol hydrofluoroalkane [HFA] MDI [or equivalent]) for at least 6 hours before SV and the treatment visits in which spirometry will be conducted (SV, randomization visit [RV], treatment visit [TV] 1, TV2, TV3, and TV4).
k. The patient is assessed as otherwise healthy, with clinically acceptable medical history, physical examination, and vital signs within the acceptable ranges for children with asthma as assessed by the investigator.
l. Each patient/parent/guardian/caregiver is capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements.
m. If female, and the patient has reached puberty and achieved menarche (as determined by the investigator), parents/guardians will be consulted to obtain permission to counsel the patient regarding the possible unknown risks associated with study medication during pregnancy. Eligible female patients of childbearing potential whom are known to be sexually active will be excluded. Additionally, a urine pregnancy test must be negative at the SV. |
(a1) Ozbiljnost bolesti: bolesnik ima trajnu astmu s forsiranim ekspiratornim volumenom u 1 sekundi (FEV1) 40 % do 90 % vrijednosti predviđene za starost, visinu i spol na posjetu za probir.
(b1) Trenutačno liječenje astme: bolesnik se trenutačno liječi jednim od sljedećih liječenja:
•stabilnom dnevnom dozom inhalacijskih kortikosteroida u rasponu od 88 do 176 mcg/dan flutikazon propionata (ili ekvivalenta) tijekom najmanje 4 tjedna (28 dana) prije posjeta za probir;
•stabilnom dnevnom dozom nekortikosteroidnog liječenja, uključujući modifikatore leukotriena, teofilin, kromone ili kratkodjelujuće β2-agoniste samostalno ili u kombinaciji tijekom najmanje 4 tjedna (28 dana) prije posjeta za probir. Ispitanici koji primaju nekortikosteroidno liječenje također će morati ispuniti kriterij nekontrolirane astme prije randomizacije;
•dnevnom dozom inhalacijskih kortikosteroida i dugodjelujućih β2-agonista (u dozi manjoj ili ekvivalentnoj flutikazon propionatu 100mcg /salmeterol 50 mcg dvaput na dan), što može biti dopušteno, ali će bolesnik morati prekinuti s tim liječenjem i početi s uzimanjem flutikazon propionata putem inhalatora s mjerenim dozama od 44 mcg, dvije inhalacije dvaput na dan za ukupno 176 mcg na dan ili ekvivalent tijekom najmanje 7 dana do ne više od 30 dana prije posjeta za probir. (c2) Reverzibilnost bolesti: bolesnik je demonstrirao najmanje 12 % reverzibilnosti vrijednosti FEV1 u 30 minuta nakon 2 do 4 inhalacije albuterola/salbutamol hidrofluoroalkana putem inhalatora s mjerenim dozama (90 mcg iz dozatora) ili ekvivalenta na posjetu za probir ili ponovnom testiranju. Bolesnici od 4 i 5 godina koji ne prođu test reverzibilnost vrijednosti FEV1 moraju pokazati najmanje 12 % reverzibilnosti PEF-a nakon 2 do 4 inhalacije albuterola/salbutamol hidrofluoroalkana putem inhalatora s mjerenim dozama (90 mcg iz dozatora) ili ekvivalent koristeći ručno mjerenje vršnog protoka. Prema diskrecijskoj odluci ispitivača može se koristiti nebulizirani albuterol/salbutamol u ukupnoj dozi od 2,5 mg. Vrijednosti reverzibilnosti od 11,50 do 11,99 zaokružit će se na 12. Dokumentirana povijest reverzibilnosti, uključujući spirograme, od najmanje 12 % na beta-agoniste u prethodnih 12 mjeseci prije posjeta za probir prihvatljiva je za bolesnike koji se u trenutku utvrđivanja početnih vrijednosti liječe inhalacijskim kortikosteroidima. Povijesni podaci nisu prihvatljivi za bolesnike na nekortikosteroidnom liječenju.
d.Roditelj ili zakonski ovlašteni zastupnik mora potpisati i datirati pisani informirani pristanak, a ispitanik mora potpisati i datirati obrazac informirane suglasnosti (ako je primjenjivo prema lokalnim propisima) prije nego što se provede bilo koji postupak povezan s ispitivanjem.
(e1) U trenutku potpisivanja informiranog pristanka/suglasnosti (posjet za probir ili pretprobir, kako je primjenjivo) bolesnik je dječak ili djevojčica od 4 do 11 godina.
f.Dijagnoza astme: bolesnik ima dijagnozu astme definiranu prema Nacionalnim institutima za zdravlje SAD-a. Dijagnoza astme postoji najmanje 3 mjeseca te je bila stabilna (definirano kao bez pogoršanja i bez promjene lijekova) najmanje 30 dana prije posjeta za probir.
(g1) Bolesnik je sposoban obaviti prihvatljivu i ponovljivu spirometriju u skladu s kriterijima ATS/ERS 2005.
h.Bolesnik je sposoban za mjerenje vršnog ekspiratornog protoka (PEF) (uz pomoć roditelja/skrbnika/njegovatelja, prema potrebi) ručnim mjeračem vršnog protoka.
i.Bolesnik je sposoban koristiti (uz pomoć roditelja/skrbnika/njegovatelja, prema potrebi) inhalator s mjerenim dozama bez razdjelnika i dahom aktivirani inhalator.
j.Bolesnik je sposoban odgoditi uzimanje (prema prosudbi ispitivača) svoje jutarnje doze lijeka za astmu (nekortikosteroidnog lijeka, inhalacijskog kortikosteroida ili ispitivanog lijeka) i lijeka za trenutačnu pomoć (na primjer, salbutamol hidrofluoroalkana iz inhalatora s mjerenim dozama [ili ekvivalenta]) tijekom najmanje 6 sati prije posjeta za probir i posjeta za liječenje na kojima će se raditi spirometrija (posjet za probir, posjet za randomizaciju, posjeti za liječenje 1, 2, 3 i 4),
k.Ispitanik je procijenjen kao inače zdrav, s klinički prihvatljivom anamnezom, rezultatima fizikalnog pregleda i mjerenja vitalnih znakova u prihvatljivim okvirima za djecu s astmom prema procjeni ispitivača.
l.Bolesnik/roditelj/skrbnik/njegovatelj sposoban je razumjeti zahtjeve, rizike i koristi od sudjelovanja u ispitivanju te je prema prosudbi ispitivača sposoban dati informirani pristanak/suglasnost te se uskladiti sa svim zahtjevima ispitivanja (primjerice, rasporedom uzimanja lijeka, posjeta, postupaka i bilježenja podataka).
m.Od roditelja ili skrbnika bolesnica koje su ušle u pubertet i dobile prvu mjesečnicu (kako utvrdi ispitivač) zatražit će se dopuštenje da se djevojke savjetuju o mogućim nepoznatim rizicima povezanima s ispitivanim lijekom tijekom trudnoće. |
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| E.4 | Principal exclusion criteria |
a. The patient has a history of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, or hypoxic seizures.
b. The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the patient’s last study-related visit (for eligible patients only, if applicable). Any patient becoming pregnant during the study will be withdrawn from the study.
c. The patient has participated in any investigational drug study within the 30 days (starting at the final follow-up visit of that study) preceding SV (or prescreening visit, as applicable), or plans to participate in another investigational drug study at any time during this study.
d. The patient has previously participated in a beclomethasone dipropionate BAI study as a randomized patient.
e. The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation.
f. The patient has been treated with any known strong cytochrome P450 (CYP) 3A4 inhibitors (eg, azole antifungals, ritonavir, clarithromycin) within 30 days before SV or plans to be treated with any strong CYP3A4 inhibitor during the study.
g. The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before SV.
h. The patient has used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco, as applicable).
i. The patient has a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract (URI or LRI), sinus, or middle ear that has not resolved at least 2 weeks before SV.
j. The patient has a history of alcohol or drug abuse within 2 years preceding SV, as applicable.
k. The patient has had an asthma exacerbation requiring oral corticosteroids within 30 days before SV, or has had any hospitalization for asthma within 2 months before SV.
l. Initiation or dose escalation of immunotherapy (administered by any route) is planned during the study period. However, patients who initiated immunotherapy 90 days or more before the screening visit (SV) and have been on a stable (maintenance) dose for 30 days or more may be considered for inclusion.
m. The patient has used immunosuppressive medications within 4 weeks (28 days) before SV.
n. The patient is unable to tolerate or unwilling to comply with the required washout periods and withholding of all applicable medications.
o. The patient has untreated oral candidiasis at SV. Patients with clinical visual evidence of oral candidiasis who agree to receive treatment and comply with appropriate medical monitoring may enter the study.
p. The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection.
q. The patient is an immediate relative of an employee of the clinical investigational center.
r. A member of the patient’s household is participating in the study at the same time. (However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened.)
s1. The patient has a disease/condition that, in the medical judgment of the investigator, would put the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study. |
a.Bolesnik ima povijest astme opasne za život definirane za ovaj plan ispitivanja kao epizoda astme koja je zahtijevala intubaciju i/ili je bila povezana s hiperkapnijom, respiratornim arestom ili hipoksičnim napadajima.
b.Bolesnica je trudna ili doji ili planira zatrudnjeti tijekom ispitivanja ili u 30 dana od zadnjeg posjeta povezanog s ispitivanjem (samo za podobne bolesnice, ako je primjenjivo). Svaka ispitanica koja zatrudni tijekom ispitivanja povući će se iz ispitivanja.
c. Bolesnik je sudjelovao u bilo kojem ispitivanju eksperimentalnog lijeka u 30 dana (počevši od zadnjeg posjeta za praćenje tog ispitivanja) prije posjeta za probir (ili posjeta za pretprobir, ako je primjenjivo) ili planira sudjelovati u drugom ispitivanju drugog eksperimentalnog lijeka u bilo kojem trenutku ispitivanja.
d.Bolesnik je prethodno kao randomizirani ispitanik sudjelovao u ispitivanju dahom aktiviranog inhalatora beklometazon dipropionata.
e.Bolesnik ima poznatu preosjetljivost na bilo koji kortikosteroid ili pomoćnu tvar iz formulacije ispitivanog lijeka ili lijeka za trenutačnu pomoć.
f.Bolesnik je liječen bilo kojim poznatim jakim inhibitorom citohroma P450 (CYP) 3A4 (na primjer, azolnim antimikoticima, ritonavirom, klaritromicinom) u 30 dana prije posjeta za probir ili se planira tijekom ispitivanja liječiti bilo kojim jakim inhibitorom CYP3A4.
g.Bolesnik je liječen bilo kojim od zabranjenih lijekova tijekom (prema planu ispitivanja) propisanog razdoblja ispiranja prije posjeta za probir.
h. Bolesnik je koristio duhanske proizvode u prošloj godini (primjerice, cigarete, cigare, duhan za žvakanje ili duhan za lule, kako je primjenjivo).
i.Bolesnik ima kulturom dokumentiranu ili pretpostavljenu bakterijsku ili virusnu infekciju gornjih ili donjih dišnih putova, sinusa ili srednjeg uha koja nije izliječena najmanje 2 tjedna prije posjeta za probir.
Napomena: bolesnici koji dobiju infekciju gornjih ili donjih dišnih putova tijekom uvodnog razdoblja mogu se ponovo probirati 2 tjedna nakon rezolucije simptoma.
j.Bolesnik ima povijest zloporabe alkohola ili droge u 2 godine prije posjeta za probir.
k.Bolesnik ima pogoršanje astme koje zahtijeva liječenje oralnim kortikosteroidima u 30 dana prije posjeta za probir ili je zbog astme bio hospitaliziran u 2 mjeseca prije posjeta za probir.
l.Planira se početak ili povećanje doze imunoterapije (davane na bilo koji način) tijekom razdoblja ispitivanja. Može se, međutim, razmatrati uključivanje bolesnika koji su počeli s imunoterapijom 90 ili više dana prije posjeta za probir te su primali stabilnu dozu (za održavanje) tijekom 30 ili više dana.
m.Bolesnik je primao lijekove za imunosupresiju u 4 tjedna (28 dana) prije posjeta za probir.
n.Bolesnik nije sposoban podnijeti ili se ne može uskladiti s traženim razdobljem ispiranja i odgađanjem uzimanja svih primjenjivih lijekova.
o.Bolesnik na posjetu za probir ima neliječenu oralnu kandidijazu. Bolesnici s kliničkim vizualnim dokazom oralne kandidijaze koji pristanu primati liječenje i usklade se s odgovarajućim medicinskim nadzorom mogu se uključiti u ispitivanje. (Napomena: azolni antimikotici su zabranjeni!)
p.Bolesnik ima anamnezu pozitivnog testa na HIV, aktivni hepatitis B ili infekciju hepatitisom C.
q.Bolesnik je blizak rođak zaposlenika ispitivačkog centra.
r.U ispitivanju istodobno sudjeluje član bolesnikova kućanstva. (Međutim, nakon što uključeni ispitanik završi ili prekine ispitivanje, može se probrati drugi bolesnik iz istoga kućanstva.)
(s1) Bolesnik ima bolest ili stanje koje bi ga, prema medicinskoj prosudbi ispitivača, zbog sudjelovanja izložilo riziku ili koje bi moglo utjecati na analize učinkovitosti ili sigurnosti ako se ta bolest ili stanje tijekom ispitivanja pogorša. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable for this study is the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) percent predicted FEV1 AUEC 0-12wk. |
| Primarna varijabla učinkovitosti za ovo ispitivanje standardizirani je, prema početnoj vrijednosti prilagođeni najniži jutarnji (prije davanja doze i prije uzimanja bronhodilatatora za trenutačnu pomoć) postotak predviđene vrijednosti FEV1 AUEC0-12wk. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary efficacy endpoint timeline is over the 12-week treatment period. |
| Primarna krajna točka efikasnosti je za vrijeme 12-tjednog perioda liječenja. |
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| E.5.2 | Secondary end point(s) |
Secondary outcome variables are as follows:
- change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF over the 12-week treatment period
- change from baseline in weekly average of daily evening PEF over the 12-week treatment period
- change from baseline in the weekly average of total daily (24-hour) use of albuterol/salbutamol inhalation aerosol (number of inhalations) over weeks 1-12
- change from baseline in weekly average of the total daily asthma symptom score (the total daily asthma symptom score is the average of the daytime and nighttime scores) over weeks 1-12
- change from baseline in trough morning (pre-dose and pre-rescue bronchodilator) FEV1 over the 12-week treatment period
- time to patient withdrawal due to meeting stopping criteria for worsening asthma during the 12-week treatment period |
Sekundarne mjere ishoda i krajnje točke za ovo ispitivanje su:
•promjene tjednog prosjeka svakodnevnih najnižih jutarnjih (prije uzimanja doze i prije primjene bronhodilatatora za trenutačnu pomoć) vršnih ekspiratornih protoka tijekom razdoblja liječenja od 12 tjedana u odnosu na početne vrijednosti;
•promjene tjednog prosjeka svakodnevnog večernjeg vršnog ekspiracijskog protoka tijekom razdoblja liječenja od 12 tjedana u odnosu na početne vrijednosti;
•promjene tjednog prosjeka ukupnog dnevnog (24 sata) korištenja inhalacijskog aerosola albuterola/salbutamola (broj inhalacija) od 1. do 12. tjedna u odnosu na početne vrijednosti;
•promjene tjednog prosjeka ukupnog dnevnog rezultata simptoma astme (ukupni dnevni rezultat simptoma astme je prosjek dnevnih i noćnih rezultata) od 1. do 12. tjedna u odnosu na početne vrijednosti;
•promjene najnižih jutarnjih (prije uzimanja doze i prije primjene bronhodilatatora za trenutačnu pomoć) vrijednosti FEV1 tijekom razdoblja liječenja od 12 tjedana u odnosu na početne vrijednosti;
•vremena do povlačenja ispitanika zbog ispunjavanja kriterija za prekid zbog pogoršanja astme tijekom razdoblja liječenja od 12 tjedana.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Evaluations for all endpoints are over Weeks 1-12. |
| Evaluacija svih krajnjih točaka se radi tijekom 1-12 tjedana |
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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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 |
| Croatia |
| Lithuania |
| Mexico |
| Poland |
| Romania |
| Serbia |
| Ukraine |
| United States |
|
| 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
|
| LVLS |
| Posljednji posjet posljednjeg ispitanika |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| 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 | 1 |
| 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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