| 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 | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives | Sub Study: Immune Response
Objective: To evaluate the difference in patient immune response against C. difficile, and to gain an understanding of how toxin binding with GT267-004 affects host immune response in comparison to vancomycin and metronidazole.
Denmark will not be participating in the sub-study
| |
| 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; to remain eligible, the patient must have ≥ 3 loose or watery bowel movements within the 24 hours preceding the first dose of study drug
• No other likely etiology for the diarrhea
• (+) C. difficile toxin assay (EIA or cellular cytotoxicity assay) or pseudomembranes on endoscopy
→ Primary CDAD patients must have demonstrated a (+) toxin assay within 72 hours prior to enrollment.
→ Recurrent CDAD patients with a history of CDAD but who have not received
therapy for a prior episode of CDAD within the 30 days pre-enrollment must have
demonstrated a (+) toxin assay within 72 hours prior to enrollment.
→ Recurrent CDAD patients who have completed therapy for a prior episode of CDAD within the 30 days pre-enrollment may be enrolled as presumed recurrent CDAD patients and can either demonstrate a (+) toxin assay within 72 hours prior to enrollment OR have a stool sample collected for a toxin assay within 24 hours post enrollment. Refer to Section 13.2 for information on patients failing to demonstrate a positive toxin assay within the 72 hours following enrollment.
Note: Pseudomembranes on endoscopy may substitute for a (+) toxin assay in all patients.
3. Negative serum 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 double barrier (condom or diaphragm, with 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 legally authorized representatives 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 | Patients 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 (e.g., severe colitis with findings such as peritoneal signs, ileus, megacolon; sepsis with hypotension that, despite adequate fluid resuscitation, requires pressor therapy; other contraindications to exclusively oral therapy for CDAD).
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+) exclusion criteria:
• K+ < 3.0 mmol (meq)/L or
• K+ < 3.5 mmol (meq)/L and history of cardiac arrhythmias or currently receiving a cardiac glycoside (e.g., digoxin or digitoxin)
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 specific for CDAD within the 5 days preceding enrollment.
Note: this includes antibiotics prescribed for other indications, but which are also effective for treating CDAD as administered (e.g., intravenous vancomycin is not effective for CDAD and so would not be exclusionary).
10. Allergy to vancomycin, metronidazole or hypersensitivity to parabens or other ingredients of the formulations.
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.
13. Inability or unwillingness to abstain from alcohol during the 14 day treatment period.
14. Previous exposure to either GT160-246 or GT267-004.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary efficacy variable will assess non-inferiority of GT267-004 versus vancomycin for Clinical Success, defined as the presence of explicit data indicating diarrhea resolution and the absence of severe abdominal discomfort due to CDAD on Day 10. If the first of the two consecutive days establishing resolution is on or before Day 10, the patient will be considered to have resolved by Day 10. | |
| 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 | Information not present in EudraCT |
| 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 | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
