Safety and Efficacy of Multiple Daily Dosing of Oral LFF571 in Patients With Moderate Clostridium Difficile Infections

This study is currently recruiting participants.
Verified June 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01232595
First received: November 1, 2010
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

This study will assess the safety and efficacy of multiple daily dosing of oral LFF571 in patients who have moderate Clostridium difficile infections.


Condition Intervention Phase
Moderate Clostridium Difficile Infection
Drug: LFF571
Drug: Vancomycin (POC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-center, Randomized, Evaluator-blind, Active-controlled,Parallel-group Design to Determine Safety, Tolerability, and Efficacy of Multiple Daily Administration of LFF571 for 10 Days in Patients With Moderate Clostridium Difficile Infections

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • POC: Difference in clinical response rate of LFF571 compared to vancomycin in patients with moderate C. difficile infections at day 12/13. [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
  • POC: Safety and tolerability of LFF571 [ Time Frame: Day 12/13 ] [ Designated as safety issue: Yes ]
    Safety assessments will include vital signs, laboratory tests, electrocardiograms (ECG), pharmacokinetic (PK) samples and adverse events. (Cohorts 1 and 2)

  • POC:Clinical response rates (clinical cure) of patients with moderate C. difficile infections to different LFF571 dose regimens and total daily doses (cohort 2). [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
    Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other therapeutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-liquid stools per day for two consecutive days

  • Cohort 2: Clinical response rate (clinical cure) of LFF571 in patients with mild and moderate C. difficile infections to different LFF571 dose regimens and total daily doses administered orally for 10 days [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
    Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other therapeutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-liquid stools per day for two consecutive days.

  • Cohort 2: Dose-response relationship of different dose regimens and total daily dose s of LFF571 [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
  • Cohort 2: Safety and tolerability of LFF571 dose regimens and total daily doses administered orally for 10 days to C. difficile infected patients. [ Time Frame: Day 12/13 ] [ Designated as safety issue: Yes ]
    Safety assessments will include vital signs, laboratory tests, electrocardiograms (ECG), pharmacokinetic (PK) samples and adverse events.


Secondary Outcome Measures:
  • POC: To evaluate the time to resolution of diarrhea during the treatment period for LFF571-treated patients (cohorts 1 and 2) [ Time Frame: End of therapy ] [ Designated as safety issue: No ]
  • POC: To evaluate the relapse rate within 30 days following completion of LFF571-treated patients (cohort 1) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • POC: To evaluate the sustained response and relapse rate within 30 days following completion of different oral LFF571 dose regimens (cohort 2) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • POC: To evaluate the fecal concentrations of LFF571 following different LFF571 dose regimens (cohort 2) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • POC: To evaluate the serum concentrations of LFF571 following different LFF571 dose regimens. (cohort 2) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Cohort 2: Time to resolution of diarrhea during the treatment period for oral LFF571 in C. difficile infected patients. [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
  • Cohort 2: Serum concentrations of oral LFF571 following different dose regimens in C. difficile infected patients. [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
  • Cohort 2: Fecal concentrations of LFF571 following different oral LFF571 dose regimens in C. Difficile infected patients. [ Time Frame: Day 12/13 ] [ Designated as safety issue: No ]
  • Cohort 2: Sustained response (sustained clinical cure) rate and clinical relapse rate at 30 days following completion of different oral LFF571 dose regimens. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other therapeutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-liquid stools per day for two consecutive days


Estimated Enrollment: 160
Study Start Date: October 2010
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LFF571 (POC) Drug: LFF571
Active Comparator: Vancomycin (POC) Drug: Vancomycin (POC)
Experimental: LFF571 Dose level 1 (cohort 2) Drug: LFF571
Experimental: LFF571 Dose level 2 (cohort 2) Drug: LFF571
Experimental: LFF571 Dose level 3 (cohort 2) Drug: LFF571
Experimental: LFF571 Dose level 4 (cohort 2) Drug: LFF571

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females between 18 and 90 years of age, inclusive.
  • Diagnosed with primary episode or first relapse of moderate C. difficile infection.

Received ≤24 hours of therapy effective for C. difficile infection prior to enrollment.

Exclusion Criteria:

  • Severe C. difficile infection
  • Expected to require more than 10 days of C. difficile infection treatment.
  • More than one prior episode of C. difficile infection within the prior 3 months.
  • Use of anti-peristaltic drugs (including tincture of opium, metoclopramide, loperamide),, cholestyramine, or colestipol

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01232595

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 47 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01232595     History of Changes
Other Study ID Numbers: CLFF571X2201, 2011-000947-26
Study First Received: November 1, 2010
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Novartis:
Clostridium difficile,
C. difficile,
CDI,
Clostridium difficile-associated disease,
CDAD,
pseudomembranous colitis,
PMC,
antibiotic-associated diarrhea

Additional relevant MeSH terms:
Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014