E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile associated diarrhoea (CDAD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012748 |
E.1.2 | Term | Diarrhoea, Clostridium difficile |
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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 |
Demonstrate that the cure rate of CDAD following treatment with PAR-101/OPT-80 is no worse than that following treatment with vancomycin.
Evaluate the safety and tolerability of PAR-101/OPT-80 in subjects with CDAD. |
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E.2.2 | Secondary objectives of the trial |
Demonstrate that the rate of recurrence of CDAD following treatment with PAR-101/OPT-80 is no worse than that following treatment with vancomycin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female in/outpatients 16 years of age or older who have CDAD as defined by - Diarrhoea:is defined as a change in bowel habits, with >3 unformed bowel movements in the 24 hours prior to randomisation, and - Presence of either toxin A or B of C. difficile in the stool within 48 hours of randomization (for metronidazole failures) or 96 hours of randomization (for subjects with ≤ 24 hours pretreatment with C. difficile therapy).
2. Female subjects of childbearing potential must be using an adequate and reliable method of contraception (eg. barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Females who are postmenopausal must have been postmenopausal at least 1 year. Subjects (both male and female) must agree to avoid conception during treatment and for four weeks following the end of study treatment.
3. All subjects will be required to sign an Informed Consent Form.
4. Opiates will be permitted as long as the subject is on a stable dose at the time of randomization and is expected to maintain this dose during the treatment period.
• PRN opiate is permitted as long as the total daily dose is not changed during the treatment period.
5. Subjects who have failed at least a full 3-day course of metronidazole but continue to meet the definition of diarrhea without any significant clinical improvement and remain toxin positive may be enrolled in the study. |
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E.4 | Principal exclusion criteria |
1. Life threatening or fulminant CDAD (WBC>30x109/L; temperature >40C; or evidence of hypotension [systolic blood pressure less than 90 mm Hg], and septic shock, peritoneal signs or significant dehydration.)
2. Toxic megacolon.
3. Previous exposure to PAR-101/OPT-80.
4. Females who arwe pregnant or breastfeeding.
5.Likelihood of death within 72 hours from any cause.
6. Concurrent use of: oral vancomycin, metronidazole, oral bacitracin, fusidic acid, rifaximin, nitazoxanide, or related drugs. If the Investigator feels the clinical imperative to begin treatment before knowing the laboratory result for stool toxin, up to 4 doses but no more than 24 hours of treatment with metronidazole and/or vancomycin will be allowed. While such pretreated subjects may be enrolled (ie. no more than 24 hours of previous therapy), it is preferred that subjects be enrolled who have not received prior CDAD treatment on this admission. The Investigators are encoursaged to identify eligible subjects whenever possible before other therapy is given and to "sensitise" their institution to this study so that subjects may be entered without prior therapy whenever possible.
7. The anticipated need to continue other antibacterials for a period exceeding seven days from study start.
8. Subjects who in the opinion of the investigator require other drugs to control diarrhea (e.g., loperamide) or which could affect peristalsis.
9. Unable or unwilling to compy with study protocol, including ingesting capsules, having blood drawn, and providing stool samples as scheduled.
10. Participation in other clinical research studies utilising an investigational agent within one month prior to screening or within five half lives of the investigational agent, whichever is longer.
11. History of ulcerative colitis or Crohn's disease.
12. Multiple occurrences (defined as more than one prior occurence) of CDAD within the past three months. Subjects presenting with the first recurrence within the three months may be enrolled.
13. Subjects the Investigator feels are inappropriate for the trial will not be included, eg. subjects with known hypersensitivity to vancomycin. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary cure rates (primary response) in the microbiologically evaluable and Modified-Intent-to-Treat (mTT) populations. |
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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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 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 | 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 |
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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
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Last post-dose visit (days 36-40) of the last subject. |
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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 | 12 |
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 | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |