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Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients

Primary Purpose

Cystic Fibrosis (CF)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MP-376
Placebo
Sponsored by
Horizon Pharma USA, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis (CF)

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria (selected):

  • > 16 years of age
  • Confirmed Diagnosis of Cystic Fibrosis
  • Positive sputum culture for P. aeruginosa within the past 18 months
  • Patients are able to elicit a forced expiratory volume in 1 second (FEV1) >/= 25% but </= 85% of predicted value at screening
  • Have received at least 3 courses of inhaled antimicrobials over the preceding 12 months
  • Clinically stable with no changes in health status within the last 30 days
  • Able to reproducibly produce sputum and perform spirometry

Exclusion Criteria (selected):

  • Use of any nebulized or systemic antibiotics within 30 days prior to baseline
  • History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
  • Evidence of acute upper within 10 days or lower respiratory infections within 30 days prior to dosing
  • Creatine clearance < 50mg/ml, aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin >/= 3 x upper limit of normal (ULN) at Screening

Sites / Locations

  • Childrens Hospital
  • Oklahoma CF Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Placebo

MP-376 120 mg QD

MP-376 240 mg QD

MP-376 240 mg BID

Arm Description

Placebo inhaled either once or twice daily via the PARI eFlow nebulizer for 28 days

MP-376 120 mg inhaled Once Daily (QD) via the PARI eFlow nebulizer for 28 days

MP-376 240 mg inhaled QD bia the PARI eFlow nebulizer for 28 days

MP-376 240 mg inhaled twice daily (BID) via the PARI eFlow nebulizer for 28 days

Outcomes

Primary Outcome Measures

Change in P. Aeruginosa Density
Patients were required to cough deeply and then spit sputum into a sterile container. The bacteria contained in the sputum sample was incubated in a laboratory and the number of P. aeruginosa colony forming units per gram of sputum (CFU/g) was determined. The difference in CFUs/g were then compared from baseline to the conclusion of the 28 day treatment period

Secondary Outcome Measures

Time to Administration of Other Anti-pseudomonal Antimicrobials
Time to administration of other anti-pseudomonal antimicrobials in patients with at least one of the following: decreased exercise tolerance, increased cough, increased sputum/chest congestion, or decreased appetite; 25th percentile data reported
Percent Change in Forced Expiratory Volume in 1 Second (FEV1)
Percent change in the amount of air the patient could exhale in 1 second
Change in FEV1 Percent Predicted
Change in the predicted percent of air the patient could exhale in one second
Changes in Respiratory Domain Scores of Cystic Fibrosis Questionnaire - Revised (CFQ-R)
Change in the score from 0 to 100 that a patient reports for their respiratory symptoms in the CFQ-R. An increase in score illustrates an improvement in symptoms. An increase of 4 or more is considered clinically significant
Changes in Susceptability Patterns of Isolated Organisms
All isolates of P. aeruginosa cultures grown from patient sputum samples were evaluated to see whether the minimum concentration of levofloxacin needed to inhibit growth of the bacteria (i.e., minimum inhibitory concentration; MIC) had increased; 2. The MIC50 and MIC90 values were calculated as the 50th percentile value and the 90th percentile value, respectively. Note that percentile values between dilution values were rounded up to the nearest dilution value

Full Information

First Posted
May 12, 2008
Last Updated
January 17, 2018
Sponsor
Horizon Pharma USA, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00677365
Brief Title
Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients
Official Title
Phase II, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability and Efficacy of Three Dosage Regimens of MP-376 Solution for Inhalation Given for 28 Days to Stable CF Patients
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Horizon Pharma USA, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients with cystic fibrosis (CF) suffer from chronic infections of the lower respiratory tract that can be caused by one or multiple bacteria, including Pseudomonas aeruginosa, which has been particularly problematic to eradicate and been implicated as the major cause of morbidity and mortality in CF patients. Aerosol delivery of antibiotics directly to the lung increases the local concentrations of antibiotic at the site of infection resulting in improved antimicrobial effects compared to systemic administration. Bacterial resistance to current aerosol antibiotic treatments indicate a need for improved therapies to treat CF patients with pulmonary infections caused by multi-drug resistant Pseudomonas aeruginosa and other bacteria. High concentrations of MP-376 delivered directly to the lung are projected to have antimicrobial effects on even the most resistant organisms.
Detailed Description
This trial will be a double-blind, placebo-controlled study to evaluate the safety, tolerability and efficacy of levofloxacin administered as MP-376 of three dosage regimens given for 28 days by the aerosol route to CF patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis (CF)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo inhaled either once or twice daily via the PARI eFlow nebulizer for 28 days
Arm Title
MP-376 120 mg QD
Arm Type
Experimental
Arm Description
MP-376 120 mg inhaled Once Daily (QD) via the PARI eFlow nebulizer for 28 days
Arm Title
MP-376 240 mg QD
Arm Type
Experimental
Arm Description
MP-376 240 mg inhaled QD bia the PARI eFlow nebulizer for 28 days
Arm Title
MP-376 240 mg BID
Arm Type
Experimental
Arm Description
MP-376 240 mg inhaled twice daily (BID) via the PARI eFlow nebulizer for 28 days
Intervention Type
Drug
Intervention Name(s)
MP-376
Other Intervention Name(s)
Levofloxacin Inhalation Solution, Aeroquin
Intervention Description
3 dose regimens of MP-376 administered twice daily (BID) or once daily (QD) for 28 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
same frequency as study drug using the same nebulizer
Primary Outcome Measure Information:
Title
Change in P. Aeruginosa Density
Description
Patients were required to cough deeply and then spit sputum into a sterile container. The bacteria contained in the sputum sample was incubated in a laboratory and the number of P. aeruginosa colony forming units per gram of sputum (CFU/g) was determined. The difference in CFUs/g were then compared from baseline to the conclusion of the 28 day treatment period
Time Frame
from baseline to end of treatment (28 days)
Secondary Outcome Measure Information:
Title
Time to Administration of Other Anti-pseudomonal Antimicrobials
Description
Time to administration of other anti-pseudomonal antimicrobials in patients with at least one of the following: decreased exercise tolerance, increased cough, increased sputum/chest congestion, or decreased appetite; 25th percentile data reported
Time Frame
from baseline until final study visit (up to 56 days)
Title
Percent Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
Percent change in the amount of air the patient could exhale in 1 second
Time Frame
from baseline to end of the 28-day treatment period (28 days)
Title
Change in FEV1 Percent Predicted
Description
Change in the predicted percent of air the patient could exhale in one second
Time Frame
from baseline to the end of the treatment 28-day treatment period (28 days)
Title
Changes in Respiratory Domain Scores of Cystic Fibrosis Questionnaire - Revised (CFQ-R)
Description
Change in the score from 0 to 100 that a patient reports for their respiratory symptoms in the CFQ-R. An increase in score illustrates an improvement in symptoms. An increase of 4 or more is considered clinically significant
Time Frame
from baseline to the end of the 28-day treatment period (28 days)
Title
Changes in Susceptability Patterns of Isolated Organisms
Description
All isolates of P. aeruginosa cultures grown from patient sputum samples were evaluated to see whether the minimum concentration of levofloxacin needed to inhibit growth of the bacteria (i.e., minimum inhibitory concentration; MIC) had increased; 2. The MIC50 and MIC90 values were calculated as the 50th percentile value and the 90th percentile value, respectively. Note that percentile values between dilution values were rounded up to the nearest dilution value
Time Frame
from baseline until the end of the 28-day treatment period (28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (selected): > 16 years of age Confirmed Diagnosis of Cystic Fibrosis Positive sputum culture for P. aeruginosa within the past 18 months Patients are able to elicit a forced expiratory volume in 1 second (FEV1) >/= 25% but </= 85% of predicted value at screening Have received at least 3 courses of inhaled antimicrobials over the preceding 12 months Clinically stable with no changes in health status within the last 30 days Able to reproducibly produce sputum and perform spirometry Exclusion Criteria (selected): Use of any nebulized or systemic antibiotics within 30 days prior to baseline History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication Evidence of acute upper within 10 days or lower respiratory infections within 30 days prior to dosing Creatine clearance < 50mg/ml, aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin >/= 3 x upper limit of normal (ULN) at Screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas J Conrad, M.D.
Organizational Affiliation
UCSD
Official's Role
Principal Investigator
Facility Information:
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Childrens Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60025
Country
United States
City
Oak Lawn
State/Province
Illinois
ZIP/Postal Code
60453
Country
United States
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89107
Country
United States
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45224
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
Oklahoma CF Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78212
Country
United States
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
City
Berlin
Country
Germany
City
Essen
Country
Germany
City
Frankfurt
Country
Germany
City
Gerlingen
Country
Germany
City
Gieben
Country
Germany
City
Kiel
Country
Germany
City
Munchen
Country
Germany
City
Tubingen
Country
Germany
City
Amsterdam
Country
Netherlands
City
Groesbeek
Country
Netherlands
City
Rotterdam
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
21471106
Citation
Geller DE, Flume PA, Staab D, Fischer R, Loutit JS, Conrad DJ; Mpex 204 Study Group. Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011 Jun 1;183(11):1510-6. doi: 10.1164/rccm.201008-1293OC. Epub 2011 Feb 25.
Results Reference
derived

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Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients

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