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

NCT01232595 | Completed Phase 2

• 2 other identifiers: CLFF571X22012011-000947-26
• Study Type: interventional
• Target: 109
• Locations: 2 countries
• Sites: 18

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.

Conditions

Moderate Clostridium Difficile Infection

Keywords

Clostridium difficile,; C. difficile,; CDI,; Clostridium difficile-associated disease,; CDAD,; pseudomembranous colitis,; PMC,; antibiotic-associated diarrhea

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (9)

• 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

Study Arms (6)

LFF571 (POC)

EXPERIMENTAL

Drug: LFF571

Vancomycin (POC)

ACTIVE COMPARATOR

Drug: Vancomycin (POC)

LFF571 Dose level 1 (cohort 2)

EXPERIMENTAL

Drug: LFF571

LFF571 Dose level 2 (cohort 2)

EXPERIMENTAL

Drug: LFF571

LFF571 Dose level 3 (cohort 2)

EXPERIMENTAL

Drug: LFF571

LFF571 Dose level 4 (cohort 2)

EXPERIMENTAL

Drug: LFF571

Interventions

LFF571 DRUG

LFF571 (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)

Vancomycin (POC) DRUG

Vancomycin (POC)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative Site

Palm Desert, California, 92211, United States

Location

Novartis Investigative Site

Bristol, Connecticut, 06010, United States

Location

Novartis Investigative Site

Clearwater, Florida, 33756, United States

Location

Novartis Investigative Site

Decatur, Georgia, 30030, United States

Location

Novartis Investigative Site

Idaho Falls, Idaho, 83404, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60637, United States

Location

Novartis Investigative Site

Michigan City, Indiana, 46360, United States

Location

Novartis Investigative Site

Topeka, Kansas, 66606, United States

Location

Novartis Investigative Site

Butte, Montana, 59701, United States

Location

Novartis Investigative Site

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43215, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Novartis Investigative Site

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78212, United States

Location

Novartis Investigative Site

Hamilton, Ontario, L8N 4A6, Canada

Location

Novartis Investigative Site

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Related Publications (2)

• 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.

  PMID: 25534727 DERIVED

• 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.

  PMID: 25534724 DERIVED

Related Links

• Results for CLFF571X2201from the Novartis Clinical Trials website

MeSH Terms

Conditions

Enterocolitis, Pseudomembranous

Interventions

LFF571; Vancomycin

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2010
• First Posted: November 2, 2010
• Study Start: October 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 19, 2020

Record last verified: 2015-03

Locations

US (14); CA (4)