E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clostridium difficile infection |
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E.1.1.1 | Medical condition in easily understood language |
Clostridium difficile infection: Infection of the intestines, which can be severe, by types of C difficile that make chemicals (toxins). Mostly affects people given antibiotics, bacteria killing drugs |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054236 |
E.1.2 | Term | Clostridium difficile infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The objectives of this study are to: (1) evaluate the safety and tolerability of VP 20621 dosed orally for up to 14 days in adults previously treated for CDI; (2) characterize the frequency and duration of stool colonization with the VP 20621 strain of C. difficile; (3) evaluate the efficacy of VP 20621 for prevention of recurrence of CDI; and (4) select a dose regimen of VP 20621 to be used in future studies. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for this protocol, subjects must:
1. Be ≥18 years of age.
2. Have been diagnosed with a qualifying episode of CDI, defined as ALL of the following:
• ≥3 unformed (loose or watery) stools within a 24-hour period.
• A documented positive C. difficile toxin assay (enzyme immunoassay [EIA] or cellular cytotoxicity assay) or DNA PCR assay for toxigenic C. difficile from a stool sample collected while the subject was symptomatic; or documented colonic pseudomembranes on endoscopy.
• The diarrhea must have been considered unlikely to have another etiology.
3. Have a qualifying episode of CDI with symptoms that started within 28 days (inclusive) prior to the day of randomization.
4. Have a qualifying episode of CDI that is either a primary episode or a first recurrence of a prior episode.
• Primary episode: the subject had no episodes of CDI (other than the qualifying episode) within 6 months before the day of randomization.
• First recurrence: the subject had only one episode of CDI (other than the qualifying episode) within 6 months before the day of randomization; the prior episode of CDI was diagnosed within 8 weeks before the onset of symptoms of the qualifying episode of CDI, and subsequently resolved (in the opinion of the investigator) at least 2 days before the onset of the qualifying episode of CDI.
5. At the time of randomization, have been treated for the qualifying episode of CDI with a single course of metronidazole or oral vancomycin for a total of at least 10 and no more than 21 days. [The treatment may have switched between metronidazole (oral or intravenous) and oral vancomycin, provided that the total treatment course was of 10 21 days duration (inclusive).]
6. Have recovered from the qualifying episode of CDI, defined as ALL of the following:
• <3 unformed (loose or watery) stools per day for at least 2 consecutive days prior to and continuing to the time of randomization.
• Abdominal discomfort must be absent or only mild for at least 2 consecutive days prior to and continuing to the time of randomization.
7. Be randomized such that the first dose of study drug is administered 1 calendar day (or at most 2 calendar days) after the end of the course of metronidazole or oral vancomycin.
8. Be willing and able to follow study procedures (e.g., study visits, provide stool samples according to the study schedule, and reliably record information in a study diary), or have a caregiver who can ensure that study procedures are followed.
9. If female, be post-menopausal (cessation of menses greater than or equal to 1 year), surgically sterile or following an acceptable non-hormonal method of birth control such as abstinence, intrauterine device, or barrier control for at least 1 complete menstrual cycle before the screening visit, or using estrogen/progestin containing products for at least 3 months before the screening visit through discharge from the study.
10. Have reliable access to telephone service to allow for contact with study personnel.
11. Have reliable access to a refrigerator for storage of study drug.
12. Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed (or have a legally authorized representative provide such consent). |
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E.4 | Principal exclusion criteria |
To be eligible for this protocol, subjects must not:
1. Have had more than 1 episode of CDI (other than the qualifying episode) within 6 months before the day of randomization.
2. Have received any of the following for treatment of the qualifying episode of CDI:
• Any anti-microbial therapy other than metronidazole or oral vancomycin
• Any immunotherapy (e.g., intravenous immunoglobulin)
• Any toxin-binding therapy (e.g., cholestyramine [Questran], colestipol [Colestid], or colesevelam [Welchol])
3. Have any of the following GI disorders:
• diagnosis of inflammatory bowel disease
• diagnosis of celiac disease
• active irritable bowel syndrome (associated with symptoms within 6 months before the day of randomization)
• active gastroparesis (associated with symptoms within 6 months before the day of randomization)
• toxic megacolon during the qualifying episode of CDI
• GI surgery within 6 weeks before the day of randomization
4. Have received loperamide (e.g., Imodium), diphenoxylate (e.g., Lomotil), or opium tincture (including laudanum and paregoric) within 3 days before the day of randomization.
5. Have an acute febrile illness (fever >38C [100.4F]) on Day 1 prior to the first dose of study drug.
6. Be planning to receive any oral or parenteral (e.g., intravenous, intramuscular, or intraperitoneal) antibacterial therapy after randomization.
7. Have any contraindication to oral/enteral therapy (e.g., severe nausea/vomiting or ileus).
8. Have an absolute neutrophil count <1000/mm3 [1.0 x 109/L] at screening.
9. Have a known immunodeficiency disorder, including but not limited to:
• HIV infection
• receiving treatment with systemic corticosteroids at a dosage equivalent to ≥10 mg/day of prednisone
• receiving myelosuppressive cancer chemotherapy
10. If outpatient at any time during the study, have household contacts (i.e., those who also occupy the subject’s particular housing unit as their residence during this time) who are <2 years of age or who have an immunodeficiency disorder (including but not limited to the conditions listed in Exclusion criterion #9).
11. Require or have an anticipated need for mechanical ventilation or vasopressors for hemodynamic support during the study.
12. Be pregnant or breastfeeding.
13. Have participated in an active dosing phase of any other investigational (unapproved) drug evaluation within 30 days prior to the screening visit.
14. Have any clinically significant medical or surgical condition that in the investigator’s or sponsor’s opinion could interfere with the administration of study drug, interpretation of study results, or compromise the safety or well-being of the subject.
15. Have a known hypersensitivity to any ingredient in the study formulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The efficacy endpoint of major interest in this study is colonization. For these analyses, colonization is defined as positive central laboratory stool C. difficile culture demonstrating VP 20621 at any time after the end of the study drug administration period. The incidence of colonization among actively treated patients will be compared with that following placebo in pairwise fashion. Secondary efficacy will include analysis of CDI recurrence within 2, 3, 4, 5, and 6 weeks of start of study drug.
The primary analysis of safety will be the evaluation of treatment-emergent adverse events, defined as any adverse event that starts during the study drug treatment period (and up to 7 days after the last dose of the study drug), and was not seen at baseline, or was seen at baseline but increased in frequency and/or severity during the study drug treatment period (and up to 7 days after the last dose of study drug). This study will also include specific evaluation of adverse events of diarrhea or loose/watery stools as reported at any time throughout the study (i.e., through Week 26). |
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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) |
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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 | 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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 9 |
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 |
Belgium |
Canada |
Germany |
Spain |
Switzerland |
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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Last visit 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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |