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

Phase 2

Completed

• Conditions: Moderate Clostridium Difficile Infection
• Interventions: Drug: LFF571; Drug: Vancomycin (POC)

• Registration Number: NCT01232595
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2010-11-01
• Study First Submitted QC: 2010-11-01
• Study First Posted: 2010-11-02
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2015-03
• Disposition First Submitted: 2020-08-20
• Disposition First Submitted QC: 2020-08-20
• Disposition First Posted: 2020-08-28
• Last Update Submitted: 2020-12-11
• Last Update Posted: 2020-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 109

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LFF571 (POC)	LFF571	-
Vancomycin (POC)	Vancomycin (POC)	-
LFF571 Dose level 1 (cohort 2)	LFF571	-
LFF571 Dose level 2 (cohort 2)	LFF571	-
LFF571 Dose level 3 (cohort 2)	LFF571	-
LFF571 Dose level 4 (cohort 2)	LFF571	-

Primary Outcome Measures

Name	Time	Method
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: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: 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.
Cohort 2: Dose-response relationship of different dose regimens and total daily dose s of LFF571	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)

Secondary Outcome Measures

Name	Time	Method
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 time to resolution of diarrhea during the treatment period for LFF571-treated patients (cohorts 1 and 2)	End of therapy
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
POC: To evaluate the relapse rate within 30 days following completion of LFF571-treated patients (cohort 1)	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: 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
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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇨🇦 Trois-Rivières, Quebec, Canada