A multi-national, multi-centre, double-blind, randomised, parallel group study to compare the safety and efficacy of 200mg PAR-101 taken q12h with 125mg Vancomycin taken q6h for ten days in subjects with Clostridium Difficile-associated diarrhea - A double-blind, randomised study of PAR-101 vs vancomycin in CDAD

Phase 1

• Conditions: Clostridium difficile associated diarrhoea (CDAD); MedDRA version: 8.1 Level: LLT Classification code 10012748 Term: Diarrhoea, Clostridium difficile

• Registration Number: EUCTR2006-004291-12-BE
• Lead Sponsor: Optimer Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-02-20
• Study Completion: 2009-12-11
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 664

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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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. Concurrent or expected use of other drugs to control diarrhoea or which could affect peristalsis (eg. loperamide or other opiates).

9. Unable ot 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: Demonstrate that the cure rate of DCAD following treatment with PAR-101 is no worse than that following treatment with vancomycin.<br><br> Evaluate the safety and tolerability of PAR-101/OPT-80 in subjects with CDAD.<br> ;Secondary Objective: Demonstrate that the rate of recurrence of CDAD following treatment with PAR-101 is no worse than that following treatment with vancomycin.;Primary end point(s): Primary cure rates (primary response) in the microbiologically evaluable and Modified-Intent-to-Treat (mTT) populations.