E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile-associated diarrhea (CDAD) |
Proljev uzrokovan bakterijom Clostridium difficille |
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E.1.1.1 | Medical condition in easily understood language |
Intestinal infection due to Clostridium difficile |
Probavna infekcija uzrokovana bakterijom Clostridium difficille |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054236 |
E.1.2 | Term | Clostridium difficile 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 determine whether the clinical response after 10-day oral administration of cadazolid is non-inferior to oral vancomycin in subjects with CDAD. |
Utvrditi je li klinički odgovor nakon 10 dana primjene oralnoga kadazolida neinferioran oralnom vankomicinu u ispitanika s proljevom uzrokovanim bakterijom Clostridium difficile. |
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E.2.2 | Secondary objectives of the trial |
To determine whether oral administration of cadazolid for 10 days is superior to oral vancomycin in the sustained clinical response of subjects with CDAD. To determine whether the resolution of diarrhea (ROD) is more rapid with oral administration of cadazolid compared to vancomycin. To determine whether CDAD symptoms, as reported by the subject, show larger improvements from baseline with oral administration of cadazolid compared to vancomycin. |
Utvrditi je li oralna primjena kadazolida tijekom 10 dana superiorna oralnom vankomicinu prema održivom kliničkom odgovoru u ispitanika s proljevom uzrokovanim bakterijom Clostridium difficile. Utvrditi je li rezolucija proljeva brža uz oralnu primjenu kadazolida u odnosu na vankomicin. Utvrditi pokazuju li simptomi proljeva uzrokovanog bakterijom Clostridium difficile koje prijavi ispitanik veća poboljšanja od početnih vrijednosti uz oralnu primjenu kadazolida u odnosu na vankomicin.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed Informed Consent. - Male or female ≥ 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception. - Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with > 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization. |
Potpisan informirani pristanak. Muškarci i žene s ≥ 18 godina starosti. Žene koje mogu zatrudnjeti moraju pristati koristiti odgovarajuću i pouzdanu metodu kontracepcije. Ispitanici s dijagnozom blagog do umjerenog ili ozbiljnog proljeva uzrokovanog bakterijom Clostridium difficile (prva pojava ili prva ponovna pojava bolesti u 3 mjeseca) s: - proljevom: promjena uobičajenog rada crijeva s > 3 neformirane stolice u 24 sata prije randomizacije i - pozitivnim testom na toksine C. difficile (na enzimskom imunotestiranju koje odobri naručitelj) na uzorku stolice pribavljenom u 72 sata prije randomizacije.
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E.4 | Principal exclusion criteria |
- More than one previous episode of CDAD in the 3-month period prior to randomization. - Evidence of life-threatening or fulminant CDAD. - Likelihood of death within 72 hours from any cause. - History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea. - Antimicrobial treatment active against CDAD administered for > 24 hours except for metronidazole treatment failures (MTF) - Known hypersensitivity or contraindication to study drugs, oxazolidinones, or quinolones. - Unable or unwilling to comply with all protocol requirements. |
Više od jedne prethodne epizode proljeva uzrokovanog bakterijom Clostridium difficile u razdoblju od 3 mjeseca prije randomizacije. Dokaz fulminantnog proljeva uzrokovanog bakterijom Clostridium difficile ili proljeva uzrokovanog bakterijom Clostridium difficile koji je opasan za život. Vjerojatnost smrti u 72 sata zbog bilo kojeg razloga. Povijest upalnih kolitisa, kronične boli u trbuhu ili kroničnog proljeva ili postojanje pozitivnog dijagnostičkog testa na enteropatogene. Nemogućnost uzimanja oralnog lijeka ili ispitanici hranjeni putem katetera (odnosno, kad bi se ispitivani lijek morao davati putem katetera za hranjenje). Antimikrobno liječenje aktivno protiv proljeva uzrokovanog bakterijom Clostridium difficile u > 24 sata, osim neuspješnih liječenja metronidazolom. Planirano liječenje nedopuštenim popratnim lijekovima. Transplantacija fekalnih mikroba, liječenje imunoglobulinima i ispitivani lijek za prevenciju ili liječenje proljeva uzrokovanog bakterijom Clostridium difficile u mjesec dana prije randomizacije. Monoklonska antitijela protiv C. difficile u 6 mjeseci prije randomizacije. Prethodna vakcinacija protiv C. difficile. Prethodno sudjelovanje u kliničkom ispitivanju kadazolida.
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Cure defined as: • Resolution of Diarrhea (ROD: ≤ 3 UBMs per day for at least 2 consecutive days) on study treatment, maintained for 2 days after End of Treatment (EOT) AND • No additional antimicrobial treatment active against CDAD or FMT between first dose and 2 days after EOT (inclusive).
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Kliničko izlječenje definirano kao: • rezolucija proljeva (≤ 3 neformirane stolice na dan tijekom najmanje 2 uzastopna dana) ispitivanim lijekom, održana tijekom 2 dana nakon posjeta za kraj liječenja, i • nepostojanje dodatnog antimikrobnog liječenja aktivnog protiv proljeva uzrokovanog bakterijom Clostridium difficile ili transplantacije fekalnih mikroba između prve doze i 2 dana nakon posjeta za kraj liječenja.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Sustained Cure defined as: • Clinical Cure AND • No Recurrence Recurrence is defined for subjects with Clinical Cure as: • New episode of diarrhea (NED: > 3 UBMs within 1 day) occurring between 3 days and 4 weeks after EOT AND • Positive C. difficile toxin stool test AND • Antimicrobial treatment active against CDAD or FMT started between 3 days and 4 weeks after EOT (or participation in the re-treatment extension with cadazolid).
Time to ROD, defined as: • The time (h) elapsed between the first dose of study drug and the time when ROD is considered achieved.
Absolute change from baseline in CDAD DaySyms Patient Reported Outcomes (PRO). CDAD DaysSyms total daily score change from baseline up to Day 12. |
Povratak bolesti je definiran za ispitanike s kliničkim izlječenjem kao: • nova epizoda proljeva (> 3 neformirane stolice u danu) koja se pojavi između 3. dana od posjeta za kraj liječenja i 5. posjeta, i • pozitivni test na toksine C. difficile u stolici, i • antimikrobno liječenje aktivno protiv proljeva uzrokovanog bakterijom Clostridium difficile ili transplantacija fekalnih mikroba započeti između 3. dana od posjeta za kraj liječenja i 5. posjeta (ili sudjelovanje u produljenju za ponovno liječenje kadazolidom).
Vrijeme do rezolucije proljeva definirano kao: • vrijeme (h) proteklo između prve doze ispitivanog lijeka i trenutka kada se rezolucija proljeva smatra ostvarenom.
Apsolutna promjena u odnosu na početne vrijednosti u Dnevniku o svakodnevnim simptomima proljeva uzrokovanog bakterijom C.diff koje prijavljuje ispitanik. Ukupna promjena dnevnog rezultata prema Dnevniku o svakodnevnim simptomima proljeva uzrokovanog bakterijom C.diff od trenutka utvrđivanja početnih vrijednosti do 12. dana
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Belgium |
Brazil |
Canada |
Chile |
Czech Republic |
Greece |
Hungary |
Israel |
Korea, Democratic People's Republic of |
Slovakia |
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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The end of the trial occurs when all the subjects have completed Visit 5 or Re-5 for those participating in the re-treatment extension with cadazolid. |
Kraj ispitivanja nastupa nakon što ispitanik završi Posjet br 5 ili Posjet br 5 u sklopu ekstenzije ispitivanja, tj. u ponovljenom liječenju. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |