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

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

Official Title
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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

Conditions
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Moderate Clostridium Difficile Infection

Intervention / Treatment
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* Drug: LFF571
* Drug: Vancomycin (POC)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFF571 (POC)<br> | Drug: LFF571<br> <br> |
| Active Comparator: Vancomycin (POC)<br> | Drug: Vancomycin (POC)<br> <br> |
| Experimental: LFF571 Dose level 1 (cohort 2)<br> | Drug: LFF571<br> <br> |
| Experimental: LFF571 Dose level 2 (cohort 2)<br> | Drug: LFF571<br> <br> |
| Experimental: LFF571 Dose level 3 (cohort 2)<br> | Drug: LFF571<br> <br> |
| Experimental: LFF571 Dose level 4 (cohort 2)<br> | Drug: LFF571<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Safety assessments will include vital signs, laboratory tests, electrocardiograms (ECG), pharmacokinetic (PK) samples and adverse events. (Cohorts 1 and 2) | 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). | 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 | Day 12/13 | 
| 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. | Day 12/13 | 
| 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. | Safety assessments will include vital signs, laboratory tests, electrocardiograms (ECG), pharmacokinetic (PK) samples and adverse events. | Day 12/13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDI,, Clostridium difficile,, C. difficile,, Clostridium difficile-associated disease,, CDAD,, pseudomembranous colitis,, PMC,, antibiotic-associated diarrhea