| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | C. difficile-associated diarrhea (CDAD) | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10012734 | |
| 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 safety and tolerability of GT267-004 versus vancomycin, and GT267-004 versus metronidazole, in patients with Clostridium difficile-associated diarrhea (CDAD).
To compare the effect of GT267-004 versus vancomycin, and GT276-004 versus metronidazole, on the resolution of CDAD.
To compare the effect of GT267-004 versus vancomycin, and GT276-004 versus metronidazole, on the rate of CDAD recurrence during the follow-up period.
To compare the safety, tolerability and efficacy of vancomycin versus metronidazole for resolution of CDAD and recurrence rates. | |
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Subjects must meet all of the following criteria in the 24 hours preceding enrollment:
1. Males and females 18 years of age or older.
2. The presence of C. difficile-associated diarrhea at the time of enrollment, defined as:
• ≥ 3 loose or watery bowel movements within the 24 hours preceding enrollment
• No other likely etiology for the diarrhea
• (+) C. difficile toxin assay (EIA or cellular cytotoxicity assay) or pseudomembranes on endoscopy
o Primary CDAD patients must have demonstrated a (+) toxin assay prior to
enrollment (can be up to 7 days prior).
o Presumed recurrent CDAD patients can either demonstrate a (+) toxin assay
prior to enrollment (can be up to 7 days prior) or have a stool sample collected
for a toxin assay within 24 hours of enrollment. Patients failing to demonstrate a
positive toxin assay within 7 days of enrollment must discontinue study drug,
undergo the End of Treatment Visit safety and Follow-Up procedures outlined in
the Protocol.
Note: Pseudomembranes on endoscopy may substitute for a (+) toxin assay in both primary and presumed recurrent CDAD patients.
3. Negative serum or urine pregnancy test (HCG) for women of childbearing potential.
4. If a woman of childbearing potential (pre-menopausal and not surgically sterilized), have an IUD or use parenteral hormonal (Depo-Provera®), abstinence, or barrier (condom or diaphragm, and spermicide) methods of contraception for the duration of the study. Women using oral contraceptives must also use a concomitant barrier method of contraception with spermicide for the duration of the study.
5. Voluntary signed/dated written informed consent to participate in this study. If a patient is unable to meet this criterion, he/she must have a legally authorized representative willing to consent to all visits and procedures as described in the consent form and scheduled by the site. Those health care providers responsible for the patient must be willing to cooperate with all visits and procedures as described in the consent form and scheduled by the site.
| |
| E.4 | Principal exclusion criteria | Subjects must not meet any of the following criteria in the 24 hours preceding enrollment:
1. Any contraindication to oral/enteral therapy (e.g., severe nausea / vomiting, ileus, toxic megacolon, severe abdominal pain / peritoneal signs).
2. Severe hepatic disease (e.g., ascites, hepatic encephalopathy or biliary obstruction).
3. Fulminant C. difficile disease requiring intravenous antibacterial therapy.
4. Any acutely life-threatening medical condition which in the judgement of the investigator would preclude completion of the study (patient should be considered sufficiently stable clinically to likely complete the 6 week study period).
5. Baseline serum potassium [K+; units are in mmol (meq)/L] exclusion criteria:
•K+ < 3.0 mmol (meq)/L
•K+ < 3.5 mmol (meq)/L and history of cardiac arrhythmias or currently receiving digoxin
6. Expected to remain on the CDAD inducing antibiotic(s) for > 7 days after enrollment.
7. Acute diarrhea of other cause (e.g., other stool pathogen, chronic gastrointestinal condition, laxative induced diarrhea or medications).
8. Chronic diarrhea with onset of diarrhea extending > 30 days prior to enrollment.
9. > 48 hours of treatment with oral or intravenous metronidazole, oral vancomycin or other antibacterial therapies for the current acute episode of CDAD within the 5 days preceding enrollment.
10. Allergy to vancomycin or metronidazole.
11. Participation in a clinical study of an investigational (unapproved) drug from 30 days preceding screening throughout study duration.
12. Women who are pregnant, or breast-feeding.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary endpoint will be non-inferiority of GT267-004 vs. vancomycin for the proportion of patients with Resolution of Diarrhea by Day 10 (ROD10) as determined by daily stool counts and average consistency. Diarrhea resolution is defined as 2 consecutive days when the patient has any number of bowel movements with an average consistency of hard or formed or no more than 2 bowel movements with an average consistency of loose or watery based on the daily Investigator Evaluation of number and average consistency of stools (average is based on evaluation of day’s overall consistency). If the first day of the two consecutive days is on or before Day 10, the patient will be considered to have resolved by Day 10. Patients who discontinue prior to resolution and Day 10 will be considered to have not resolved by Day 10. Patients who have a recurrence prior to the end of study Day 10 will be considered to have not resolved by Day 10. The primary analysis of ROD10 will be an assessment of non-inferiority. The proportions of patients with ROD will be tabulated by treatment group. A one-sided 95% lower confidence bound will be estimated for the difference in proportion between treatment groups (difference = test – referent). Non-inferiority will be established if the lower bound of this interval is greater than -0.10. If non-inferiority is established for the test product and a numerical advantage is observed, then superiority of GT267-004 over vancomycin will be assessed based on a one-sided Z-test for comparison of proportions. | |
| 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 | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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.8.3 | 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | | Last patient, last visit. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
