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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01232595

Collaborator

(none)

109

Enrollment

Locations

Arms

Duration (Months)

6.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Moderate Clostridium Difficile Infection	Drug: LFF571 Drug: Vancomycin (POC)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

109 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

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. [Day 12/13]
POC: Safety and tolerability of LFF571 [Day 12/13]
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). [Day 12/13]
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 [Day 12/13]
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 [Day 12/13]
Cohort 2: Safety and tolerability of LFF571 dose regimens and total daily doses administered orally for 10 days to C. difficile infected patients. [Day 12/13]
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) [End of therapy]
POC: To evaluate the relapse rate within 30 days following completion of LFF571-treated patients (cohort 1) [30 days]
POC: To evaluate the sustained response and relapse rate within 30 days following completion of different oral LFF571 dose regimens (cohort 2) [30 days]
POC: To evaluate the fecal concentrations of LFF571 following different LFF571 dose regimens (cohort 2) [30 days]
POC: To evaluate the serum concentrations of LFF571 following different LFF571 dose regimens. (cohort 2) [30 days]
Cohort 2: Time to resolution of diarrhea during the treatment period for oral LFF571 in C. difficile infected patients. [Day 12/13]
Cohort 2: Serum concentrations of oral LFF571 following different dose regimens in C. difficile infected patients. [Day 12/13]
Cohort 2: Fecal concentrations of LFF571 following different oral LFF571 dose regimens in C. Difficile infected patients. [Day 12/13]
Cohort 2: Sustained response (sustained clinical cure) rate and clinical relapse rate at 30 days following completion of different oral LFF571 dose regimens. [30 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Palm Desert	California	United States	92211
2	Novartis Investigative Site	Bristol	Connecticut	United States	06010
3	Novartis Investigative Site	Clearwater	Florida	United States	33756
4	Novartis Investigative Site	Decatur	Georgia	United States	30030
5	Novartis Investigative Site	Idaho Falls	Idaho	United States	83404
6	Novartis Investigative Site	Chicago	Illinois	United States	60637
7	Novartis Investigative Site	Michigan City	Indiana	United States	46360
8	Novartis Investigative Site	Topeka	Kansas	United States	66606
9	Novartis Investigative Site	Butte	Montana	United States	59701
10	Novartis Investigative Site	Durham	North Carolina	United States	27710
11	Novartis Investigative Site	Columbus	Ohio	United States	43215
12	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73112
13	Novartis Investigative Site	Charleston	South Carolina	United States	29425
14	Novartis Investigative Site	San Antonio	Texas	United States	78212
15	Novartis Investigative Site	Hamilton	Ontario	Canada	L8N 4A6
16	Novartis Investigative Site	Chicoutimi	Quebec	Canada	G7H 5H6
17	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
18	Novartis Investigative Site	Trois-Rivières	Quebec	Canada	G8Z 3R9