E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Bacterial Skin and Skin Structure Infections |
Akutne bakterijske kožne infekcije i infekcije kožnih struktura |
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E.1.1.1 | Medical condition in easily understood language |
Acute Bacterial Skin and Skin Structure Infections |
Akutne bakterijske kožne infekcije i infekcije kožnih struktura |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052891 |
E.1.2 | Term | Skin bacterial infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 compare the efficacy of treatment with a single dose of dalbavancin 1500 mg to treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with known or suspected Gram-positive abSSSI at 48 -72 hours after initiation of treatment. |
Usporediti učinkovitost terapije jednokratnom dozom dalbavancina 1500 mg u odnosu na terapiju s dvije doze dalbavancina (1000 mg 1. dana, a zatim 500 mg 8. dana) za liječenje pacijenata s poznatom ili suspektnom Gram-pozitivnom akutnom bakterijskom infekcijom kože i kožnih struktura (abSSSI) nakon 48 72 sata od početka terapije. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy outcomes at relevant time points as well as the safety profile of treatment with a single dose of dalbavancin 1500 mg versus the safety profile of treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with known or suspected Gram-positive abSSSI. To compare the population PK profiles of a single dose of dalbavancin 1500 mg versus the two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with acute bacterial skin and skin structure infections and to estimate and compare the PK/PD relationship of each dose regimen. |
Usporediti učinkovitost rezultata u određenim vremenskim točkama kao i profil sigurnosti terapije s jednokratnom dozom dalbavancina 1500 mg u odnosu na profil sigurnosti terapije s dvije doze dalbavancina (1000 mg 1. dana, a zatim 500 mg 8. dana) za liječenje pacijenata s poznatom ili suspektnom Gram-pozitivnom akutnom bakterijskom infekcijom kože i kožnih struktura (abSSSI). Usporediti FK profile populacije liječene jednokratnom dozom dalbavancina 1500 mg u odnosu na terapiju s dvije doze dalbavancina (1000 mg 1. dana, a zatim 500 mg 8. dana) za liječenje pacijenata s akutnom bakterijskom kožnom infekcijom i infekcijom kožnih struktura i za procjenu i usporedbu FK/FD odnosa svakog doznog režima.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic sub-study to compare the population PK profiles of a single dose of dalbavancin 1500 mg versus the two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with acute bacterial skin and skin structure infections and to estimate and compare the PK/PD relationship of each dose regimen.The PK substudy will be conducted at selected sites on a voluntary basis. It has been determined that up to 125 subjects will have pharmacokinetic samples drawn in this study.Patients enrolled in the treatment portion of the study may elect not to participate in the PK substudy. |
Farmakokinetičko podispitivanje usporedbe FK profila populacije liječene jednokratnom dozom dalbavancina 1500 mg u odnosu na terapiju s dvije doze dalbavancina (1000 mg 1. dana, a zatim 500 mg 8. dana) za liječenje pacijenata s akutnom bakterijskom kožnom infekcijom i infekcijom kožnih struktura i za procjenu i usporedbu FK/FD odnosa svakog doznog režima. Farmakokinetičko podispitivanje biti će provedeno na odabranim centrima na osnovi dobrovoljnog pristanka ispitanika. Određeno je da će se uzorci krvi za FK podispitivanje uzeti na uzorku od 125 ispitanika. ispitanici uključeni u glavno ispitivanje mogu odabrati da ne sudjeluju u FK podispitivanju.
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E.3 | Principal inclusion criteria |
1. Male or female patients, 18-85 years of age. 2. A personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 3. Patients having an abSSSI (suspected or confirmed to be caused by Gram-positive bacteria) defined for purposes of this study as an infection either involving deeper soft tissue or requiring significant surgical intervention: (a) Major cutaneous abscess characterized as a collection of pus within the dermis or deeper that is accompanied by erythema, edema and/or induration which: i. requires surgical incision and drainage, and ii. is associated with cellulitis such that the total affected area involves at least 75 cm2 of erythema, and iii. is defined by a margin of erythema that is ≥ 5 cm from the rim of induration or edema that defines the border of the abscess in all directions, or, iv. alternatively, involves the central face and is associated with an area of erythema of at least 50 cm2 and a margin ≥ 3 cm in all directions from the abscess rim (b) Surgical site or traumatic wound infection characterized by purulent drainage with surrounding erythema, edema and/or induration which occurred within 30 days after the trauma or surgery and is associated with cellulitis such that i. the total affected area involves at least 75 cm2 of erythema, and ii. is defined by a margin of erythema in at least one direction that is ≥ 5 cm from the edge of the wound, or iii. alternatively, involves the central face and is associated with an affected area of at least 50 cm2 and has a margin of erythema in at least one direction ≥ 3 cm from the wound edge (c) Cellulitis, defined as a diffuse skin infection characterized by spreading areas of erythema, edema and/or induration and i. is associated with erythema that involves at least 75 cm2 of surface area, or ii. alternatively, cellulitis of the central face that is associated with an affected area of at least 50 cm2 4. In addition to the requirement for erythema, all patients are required to have at least two (2) of the following signs of abSSSI (a) Purulent drainage/discharge (b) Fluctuance (c) Heat/localized warmth (d) Tenderness to palpation (e) Swelling/induration 5. Patients must present with at least ONE of the following systemic signs of infection: (a) An elevated body temperature 38C/100.4F as measured by the patient/caregiver or investigator within 24 hours of baseline; (b) White blood cell count > 12,000 cells/mm3; (c) A manually performed white blood differential count with ≥ 10% band forms, regardless of peripheral white blood cell count. 6. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
1. Pacijenti i pacijentice u dobi od 18 do 85 godina. 2. Osobno potpisani i datirani dokument informiranog pristanka koji pokazuje da je pacijent (ili zakonski prihvatljiv predstavnik) bio informiran o svim bitnim aspektima ispitivanja. 3. Pacijenti koji imaju infekciju abSSSI (suspektnu ili potvrđenu uzrokovanu Gram-pozitivnom bakterijom) koja je za potrebe ovog ispitivanja definirana kao infekcija bilo da uključuje dublje meko tkivo ili zahtijeva značajnu kiruršku intervenciju: (a) Veći kožni apsces karakteriziran kao nakupina gnoja unutar dermisa ili dublje koji je popraćen eritemom, edemom i/ili induracijom koji: i. zahtijeva kiruršku inciziju i drenažu, i ii. povezan sa celulitisom tako da ukupna zahvaćena površina uključuje najmanje 75 cm2 eritema, i iii. definiran rubom eritema koji se nalazi ≥ 5 cm od ruba induracije ili edema koji definira granicu apscesa u svim smjerovima, ili iv. pak, uključuje središnju stranu, a povezan je s površinom eritema od najmanje 50 cm2, uz rub od ≥ 3 cm u svim smjerovima od ruba apscesa (b) Infekcija na kirurškom mjestu ili traumatskoj rani karakterizirana gnojnom drenažom s okolnim eritemom, edemom i/ili induracijom koja se pojavila u roku od 30 dana nakon traume ili operacije te je povezana s celulitisom tako da i. ukupna zahvaćena površina uključuje najmanje 75 cm2 eritema, i ii. definirana je rubom eritema koji se nalazi u najmanje jednom smjeru ≥ 5 cm od ruba rane, ili, iii. pak, uključuje središnju stranu, a povezana je sa zahvaćenom površinom od najmanje 50 cm2 i ima rub eritema u najmanje jednom smjeru ≥ 3 cm od ruba rane (c) Celulitis, definiran kao difuzna infekcija kože karakterizirana širenjem područja eritema, edema i/ili induracije i i. povezan s eritemom tako da uključuje najmanje 75 cm2 površine, ili ii. pak uključuje središnju stranu celulitisa, koja je povezana sa zahvaćenom površinom od najmanje 50 cm2 4. Osim uvjeta za eritem, svi pacijenti moraju imati najmanje dva (2) od sljedećih znakova abSSSI-a (a) gnojna drenaža/iscjedak (b) fluktuacija (c) užarenost/lokalizirana toplina (d) osjetljivost na palpitaciju (e) otok/induracija 5. Pacijenti moraju imati najmanje JEDAN od sljedećih sistemskih znakova infekcije: (a) povišenu tjelesnu temperaturu 38 C/100,4 F koju je izmjerio pacijent/skrbnik ili ispitivač u roku od 24 sata od početnog posjeta; (b) broj leukocita > 12.000 leukocita/mm3; (c) ručno izvedenu diferencijalnu sliku leukocita ≥ 10% štapićastog oblika, bez obzira na perifernu sliku bijelih krvnih stanica. 6. Pacijent mora biti spreman i sposoban dolaziti na zakazane posjete, pridržavati se plana liječenja, laboratorijskih pretraga i drugih postupaka u ispitivanju.
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E.4 | Principal exclusion criteria |
1. Patients with a contra-indication to the administration of dalbavancin (see Section 5.4.1) such as hypersensitivity to any of the glycopeptide agents. 2. Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant. 3. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg for more than 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure. 4. Participation in another study of an investigational drug or device within 30 days prior to enrollment. 5. Receipt of a systemically or topically administered antibiotic with a Gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the abSSSI within 14 days prior to randomization. An exception is allowed for patients receiving a single dose of a short-acting (half-life ≤ 12 hours) antibacterial drug prior to randomization; up to 25% of subjects may have received such therapy. 6. Infection due to an organism known prior to study entry to be resistant to dalbavancin or vancomycin (vancomycin MIC > 8 g/mL). 7. Patients with evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis; endovascular infection, such as clinical and/or echocardiographic evidence of endocarditis or septic thrombophlebitis. 8. Infections caused exclusively by Gram-negative bacteria (without Gram-positive bacteria present) and infections caused by fungi, whether alone or in combination with a bacterial pathogen. 9. Venous catheter entry site infection. 10. Infections involving a diabetic foot ulceration, perirectal abscess or a decubitus ulcer. 11. Patient with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, hemodialysis catheter, implantable pacemaker or defibrillator, intra-aortic balloon pump, left ventricular assist device, a peritoneal dialysis catheter, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter. 12. Gram-negative bacteremia, even in the presence of Gram-positive infection or Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the study, or is subsequently found to have been present at Baseline, the patient should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia. Such patients must have an EOT visit performed within 3 calendar days after discontinuing study medication and are required to have AEs reported through Final Visit. 13. Patients whose abSSSI is the result of having sustained full or partial thickness burns.14. Patients with an infection involving a limb with evidence of critical ischemia of an affected limb defined as any of the following criteria: absent or abnormal Doppler wave forms, toe blood pressure of < 45 mm Hg, ankle brachial index < 0.5, and/ or critical ischemia as assessed by a vascular surgeon. 15. Patients with abSSSI such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure. 16. Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study. 17. Anticipated need of antibiotic therapy for longer than 14 days. 18. Patients who are placed in a hyperbaric chamber as adjunctive therapy for the abSSSI. 19. More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the abSSSI, or patients who are expected to require more than 2 such interventions. 20. Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity). 21. Absolute neutrophil count < 500 cells/mm3. 22. Known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count < 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count. 23. Patients with a recent bone marrow transplant (in post-transplant hospital stay). 24. Patients receiving oral steroids > 20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation. 25. Patients with a rapidly fatal illness, who are not expected to survive for 3 months. 26. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation |
1. Pacijenti s kontraindikacijom za primjenu dalbavancina (vidjeti Odjeljak 5.4.1), kao što je preosjetljivost na bilo koji agens glikopeptida. 2. Žene u fertilnoj dobi koje nisu u mogućnosti poduzeti odgovarajuće kontracepcijske mjere opreza, imaju pozitivan rezultat na trudnoću unutar 24 sata prije ulaska u ispitivanje, znaju da su trudne ili trenutno doje. 3. Pacijenti s teškim šokom definiranim kao sistolički krvni tlak < 90 mm Hg tijekom više od 2 sata usprkos adekvatnoj reanimaciji tekućinama, s dokazom hipoperfuzije ili potrebom za simpatomimetičkim lijekovima za održavanje krvnog tlaka. 4. Sudjelovanje u drugom ispitivanju nekog ispitivanog lijeka ili uređaja unutar 30 dana prije upisa. 5. Primanje sistemskog ili topikalnog antibiotika iz Gram-pozitivnog spektra koji ostvaruje terapijske koncentracije u serumu ili na mjestu abSSSI-a unutar 14 dana prije randomizacije. Iznimka je dopuštena u pacijenata koji primaju jednokratnu dozu kratkog djelovanja (poluživot ≤ 12 sati), antibakterijski lijek prije randomizacije; do 25% ispitanika mogu primati takvu terapiju. 6 Infekcija uzrokovana organizmom za koji je prije ulaska u ispitivanje bilo poznato da je otporan na dalbavancin ili vankomicin (vankomicin MIC > 8 g/ml). 7. Pacijenti s dokazanim meningitisom, nekrotizirajućim fascitisom, plinskom gangrenom, gangrenom, septičkim artritisom, osteomijelitisom; endovaskularnom infekcijom, kao što su klinički i/ili ehokardiografski dokazani endokarditis ili septički tromboflebitis. 8. Infekcije uzrokovane isključivo Gram-negativnim bakterijama (bez prisutnih Gram-pozitivnih bakterija) i infekcije uzrokovane gljivicama, bilo da su same ili u kombinaciji s patogenim bakterijama. 9. Infekcija na mjestu primjene venskog katetera. 10. Infekcije koje uključuju ulceracije dijabetičkog stopala, perirektalni apsces ili dekubitalni ulkus. 11. Pacijent sa zaraženim uređajem, čak i ako je uređaj uklonjen. Primjeri uključuju infekcije od: protetskog srčanog zaliska, vaskularnog grafta, baterije srčanog elektrostimulatora, proteze zgloba, katetera za hemodijalizu, implantiranog srčanog elektrostimulatora ili defibrilatora, intra-aortne balonske pumpe, pomoćnog uređaja za lijevi ventrikul, katetera za peritonejsku dijalizu ili neurokirurških uređaja kao što su ventrikuloperitonejski šant, monitor za intrakranijalni tlak ili epiduralni kateter. 12. Gram-negativna bakterijemija, čak i u prisutnosti Gram-pozitivne infekcije ili Gram-pozitivne bakterijemije. Napomena: Ako se Gram-negativna bakterijemija razvije tijekom ispitivanja, ili se naknadno utvrdi da je bila prisutna na početku liječenja, pacijent bi trebao biti uklonjen iz ispitivanja i primiti odgovarajući(e) antibiotik(e) za liječenje Gram-negativne bakterijemije. Takvi pacijenti moraju obaviti završni posjet u liječenju (EOT) u roku od 3 kalendarska dana nakon prekida primanja ispitivanog lijeka i moraju izvijestiti o nuspojavama (AE) prilikom konačnog posjeta. 13. Pacijenti kod kojih je infekcija abSSSI nastala nakon što su pretrpjeli opekline pune ili djelomične debljine kože. 14. Pacijenti s infekcijom koja uključuje ekstremitet s dokazima o kritičnoj ishemiji zahvaćenog ekstremiteta definirana bilo kojim od sljedećih kriterija: odsutni ili abnormalni oblici Doppler vala, krvni tlak nožnog prsta < 45 mm Hg, brahijalni indeks gležnja < 0,5 i/ili kritična ishemija prema procjeni vaskularnog kirurga. 15. Pacijenti s infekcijom abSSSI poput površinskog/jednostavnog celulitisa/erizipela, lezije od impetiga, furunkula ili jednostavnog apscesa koji zahtijeva samo kiruršku drenažu. 16. Istovremeno stanje koje zahtijeva neku antibiotsku terapiju koja bi mogla utjecati na procjenu ispitivanog lijeka za stanje koje se ispituje. 17. Predviđena primjena antibiotske terapije dulje od 14 dana. 18. Pacijenti koji su smješteni u hiperbaričnu komoru kao pomoćne terapije za abSSSI. 19. Više od 2 kirurške intervencije (definirane kao postupci koji se provode sterilnom tehnikom i obično se ne mogu obavljati uz postelju) za abSSSI ili pacijenti za koje se očekuje da će trebati više od 2 takve intervencije. 20. Zdravstvena stanja u kojima kronična upala može spriječiti procjenu kliničkog odgovora na terapiju i nakon uspješnog liječenja (npr. kronični stazni dermatitis donjih ekstremiteta). 21. Apsolutni broj neutrofila < 500 stanica/mm3. 22. Pacijenti s poznatom ili suspektnom infekcijom virusom humane imunodeficijencije (HIV) s brojem CD4 stanica < 200 stanica/mm3 s prošlim ili trenutnim stanjem definiranim sindromom stečene imunodeficijencije (AIDS) i nepoznat broj CD4 stanica. 23. Pac.s nedavnom transplantacijom koštane srži (u posttransplantacijskom boravku u bolnici). 24. Pac. koji primaju peroralne steroide > 20 mg prednizolona dnevno (ili ekvivalent) ili primaju imunosupresivne lijekove nakon transplantacije organa. 25. Pacijenti s brzo napredujućom fatalnom bolesti, za koje se ne očekuje da će preživjeti više od 3 mjeseca.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy assessment will be the clinical status (success or failure) in the ITT population at 48-72 hours after initiation of therapy; The primary outcome measure for efficacy evaluation will be the percentage of patients in each treatment group who demonstrate a clinical response at 48-72 hours after the initiation of therapy with study medication, with clinical response defined as follows: • The patient is alive; • The patient has received no rescue therapy for abSSSI; and • Examination of the patient’s abSSSI lesion demonstrates a decrease of ≥20% in lesion area (calculated as the longest length multiplied by the longest perpendicular width) relative to the baseline measurement. For the primary efficacy evaluation, these percentages will be compared using an Intention to Treat (ITT) population comprised of all randomized subjects. |
Primarni rezultat mjera za procjenu učinkovitosti bit će klinički status (uspjeh ili neuspjeh) u populaciji s namjerom liječenja (eng. Intention to Treat, ITT) na 48-72 sata nakon početka terapije. Primarni rezultat mjera za procjenu učinkovitosti bit će postotak pacijenata u svakoj terapijskoj skupini, koji pokazuju klinički odgovor na 48-72 sata nakon početka terapije ispitivanim lijekom, s kliničkim odgovorom koji je definiran na sljedeći način: • pacijent je živ; • pacijent nije dobio nikakvu simptomatsku terapiju za abSSSI; i • pregled abSSSI lezija na pacijentu pokazuje pad ≥ 20% u području lezije (izračunata kao najveća duljina pomnožena s najduljom okomitom širinom) u odnosu na mjerenja osnovnih vrijednosti. Za primarnu procjenu učinkovitosti, ovi će se postoci usporediti primjenom populacije s namjerom liječenja (eng. Intention to Treat, ITT), koja se sastoji od svih randomiziranih ispitanika. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
48-72 hours after the initiation of therapy with study medication |
48-72 sata nakon početka terapije ispitivanim lijekom |
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E.5.2 | Secondary end point(s) |
The secondary outcome measure for efficacy evaluation (Clinical Status - ) will be the percentage of patients in each treatment group who demonstrate clinical success at Day 28 (+/- 2 days). |
Sekundarni rezultat mjera za procjenu učinkovitosti bit će (klinički status - ) postotak ispitanika u svakoj terapijskoj grupi koji pokažu klinički uspjeh na 28. dan (+/- 2 dana) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 28 (+/- 2 days). |
28. dan (+/- 2 dana) |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 |
Režim doze dalbavancina (1000 mg 1. dana, a zatim 500 mg 8. dana) |
Two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) |
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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 | 26 |
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 |
Bulgaria |
Croatia |
Estonia |
Georgia |
Hungary |
Latvia |
Lithuania |
Romania |
Russian Federation |
Serbia |
Ukraine |
United States |
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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
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LSLV |
Posljednji posjet posljednjeg pacijenta |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |