E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile-associated diarrhea (CDAD) |
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E.1.1.1 | Medical condition in easily understood language |
Intestinal infection due to Clostridium difficile |
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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 | 18.1 |
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. |
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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. |
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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 |
- PRO sub-study: A multi-center sub-study to validate the CDAD-DaySyms (Clostridium difficile-associated diarrhea – Daily Symptoms) PRO in subjects with CDAD participating in study AC-061A301 or AC-061A302 Final version 3 dated 30Nov15 objective: to demonstrate the content and psychometric validity of the CDAD-DaySyms (Clostridium difficile-associated diarrhea – Daily Symptoms) PRO (Patient-Reported Outcome) and its appropriateness for the population of subjects with CDAD.
-Gut microbiome sub-study: A multi-center sub-study to assess the effects of cadazolid versus vancomycin on the composition of intestinal microbiota of subjects with Clostridium difficile-associated diarrhea (CDAD) participating in study AC-061A301 or AC-061A302. Final version 1 dated 11Mar15 objective: The objective of this sub-study is to assess the effect of cadazolid versus vancomycin on the composition of intestinal microbiota in CDAD subjects in study AC-061A301 and study AC-061A302. |
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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 unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile GDH and toxin test on the same stool sample produced within 72 hours prior to randomization. |
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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 or known positive diagnostic test for enteropathogens. - 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. |
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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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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 after EOT and Visit 5 AND • Positive C. difficile GDH and toxin stool test on the same stool sample AND • Antimicrobial treatment active against CDAD or FMT started between 3 days after EOT and Visit 5 (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. |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Croatia |
Czech Republic |
Greece |
Hungary |
Israel |
Korea, Democratic People's Republic of |
Romania |
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. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
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 |