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

Primary Purpose

Moderate Clostridium Difficile Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LFF571
Vancomycin (POC)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Moderate Clostridium Difficile Infection focused on measuring Clostridium difficile,, C. difficile,, CDI,, Clostridium difficile-associated disease,, CDAD,, pseudomembranous colitis,, PMC,, antibiotic-associated diarrhea

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

LFF571 (POC)

Vancomycin (POC)

LFF571 Dose level 1 (cohort 2)

LFF571 Dose level 2 (cohort 2)

LFF571 Dose level 3 (cohort 2)

LFF571 Dose level 4 (cohort 2)

Arm Description

Outcomes

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.
POC: Safety and tolerability of LFF571
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).
Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other theraperutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-lliquid 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
Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other theraperutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-lliquid stools per day for two consecutive days.
Cohort 2: Dose-response relationship of different dose regimens and total daily dose s of LFF571
Cohort 2: Safety and tolerability of LFF571 dose regimens and total daily doses administered orally for 10 days to C. difficile infected patients.
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)
POC: To evaluate the relapse rate within 30 days following completion of LFF571-treated patients (cohort 1)
POC: To evaluate the sustained response and relapse rate within 30 days following completion of different oral LFF571 dose regimens (cohort 2)
POC: To evaluate the fecal concentrations of LFF571 following different LFF571 dose regimens (cohort 2)
POC: To evaluate the serum concentrations of LFF571 following different LFF571 dose regimens. (cohort 2)
Cohort 2: Time to resolution of diarrhea during the treatment period for oral LFF571 in C. difficile infected patients.
Cohort 2: Serum concentrations of oral LFF571 following different dose regimens in C. difficile infected patients.
Cohort 2: Fecal concentrations of LFF571 following different oral LFF571 dose regimens in C. Difficile infected patients.
Cohort 2: Sustained response (sustained clinical cure) rate and clinical relapse rate at 30 days following completion of different oral LFF571 dose regimens.
Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other theraperutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-lliquid stools per day for two consecutive days

Full Information

First Posted
November 1, 2010
Last Updated
December 11, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01232595
Brief Title
Safety and Efficacy of Multiple Daily Dosing of Oral LFF571 in Patients With Moderate Clostridium Difficile Infections
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moderate Clostridium Difficile Infection
Keywords
Clostridium difficile,, C. difficile,, CDI,, Clostridium difficile-associated disease,, CDAD,, pseudomembranous colitis,, PMC,, antibiotic-associated diarrhea

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
109 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LFF571 (POC)
Arm Type
Experimental
Arm Title
Vancomycin (POC)
Arm Type
Active Comparator
Arm Title
LFF571 Dose level 1 (cohort 2)
Arm Type
Experimental
Arm Title
LFF571 Dose level 2 (cohort 2)
Arm Type
Experimental
Arm Title
LFF571 Dose level 3 (cohort 2)
Arm Type
Experimental
Arm Title
LFF571 Dose level 4 (cohort 2)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LFF571
Intervention Type
Drug
Intervention Name(s)
Vancomycin (POC)
Primary Outcome Measure Information:
Title
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
Title
POC: Safety and tolerability of LFF571
Description
Safety assessments will include vital signs, laboratory tests, electrocardiograms (ECG), pharmacokinetic (PK) samples and adverse events. (Cohorts 1 and 2)
Time Frame
Day 12/13
Title
POC:Clinical response rates (clinical cure) of patients with moderate C. difficile infections to different LFF571 dose regimens and total daily doses (cohort 2).
Description
Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other theraperutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-lliquid stools per day for two consecutive days
Time Frame
Day 12/13
Title
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
Description
Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other theraperutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-lliquid stools per day for two consecutive days.
Time Frame
Day 12/13
Title
Cohort 2: Dose-response relationship of different dose regimens and total daily dose s of LFF571
Time Frame
Day 12/13
Title
Cohort 2: Safety and tolerability of LFF571 dose regimens and total daily doses administered orally for 10 days to C. difficile infected patients.
Description
Safety assessments will include vital signs, laboratory tests, electrocardiograms (ECG), pharmacokinetic (PK) samples and adverse events.
Time Frame
Day 12/13
Secondary Outcome Measure Information:
Title
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
Title
POC: To evaluate the relapse rate within 30 days following completion of LFF571-treated patients (cohort 1)
Time Frame
30 days
Title
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
Title
POC: To evaluate the fecal concentrations of LFF571 following different LFF571 dose regimens (cohort 2)
Time Frame
30 days
Title
POC: To evaluate the serum concentrations of LFF571 following different LFF571 dose regimens. (cohort 2)
Time Frame
30 days
Title
Cohort 2: Time to resolution of diarrhea during the treatment period for oral LFF571 in C. difficile infected patients.
Time Frame
Day 12/13
Title
Cohort 2: Serum concentrations of oral LFF571 following different dose regimens in C. difficile infected patients.
Time Frame
Day 12/13
Title
Cohort 2: Fecal concentrations of LFF571 following different oral LFF571 dose regimens in C. Difficile infected patients.
Time Frame
Day 12/13
Title
Cohort 2: Sustained response (sustained clinical cure) rate and clinical relapse rate at 30 days following completion of different oral LFF571 dose regimens.
Description
Clinical cure is resolution or improvement of symptoms and signs of C. difficile infection such that additional or alternative antimicrobial therapy or other theraperutic intervention is not needed. In addition, patient must have absence of fever for two consecutive days and <3 non-lliquid stools per day for two consecutive days
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Palm Desert
State/Province
California
ZIP/Postal Code
92211
Country
United States
Facility Name
Novartis Investigative Site
City
Bristol
State/Province
Connecticut
ZIP/Postal Code
06010
Country
United States
Facility Name
Novartis Investigative Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Novartis Investigative Site
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
Novartis Investigative Site
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Novartis Investigative Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Novartis Investigative Site
City
Michigan City
State/Province
Indiana
ZIP/Postal Code
46360
Country
United States
Facility Name
Novartis Investigative Site
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606
Country
United States
Facility Name
Novartis Investigative Site
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Novartis Investigative Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Novartis Investigative Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
Facility Name
Novartis Investigative Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Novartis Investigative Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Novartis Investigative Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78212
Country
United States
Facility Name
Novartis Investigative Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
Novartis Investigative Site
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 5H6
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Novartis Investigative Site
City
Trois-Rivières
State/Province
Quebec
ZIP/Postal Code
G8Z 3R9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
25534727
Citation
Mullane K, Lee C, Bressler A, Buitrago M, Weiss K, Dabovic K, Praestgaard J, Leeds JA, Blais J, Pertel P. Multicenter, randomized clinical trial to compare the safety and efficacy of LFF571 and vancomycin for Clostridium difficile infections. Antimicrob Agents Chemother. 2015 Mar;59(3):1435-40. doi: 10.1128/AAC.04251-14. Epub 2014 Dec 22.
Results Reference
derived
PubMed Identifier
25534724
Citation
Bhansali SG, Mullane K, Ting LS, Leeds JA, Dabovic K, Praestgaard J, Pertel P. Pharmacokinetics of LFF571 and vancomycin in patients with moderate Clostridium difficile infections. Antimicrob Agents Chemother. 2015 Mar;59(3):1441-5. doi: 10.1128/AAC.04252-14. Epub 2014 Dec 22.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=12263
Description
Results for CLFF571X2201from the Novartis Clinical Trials website

Learn more about this trial

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

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