Clinical trial NCT01180634: MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis
Official title: A Phase 3, Multi-Center, Multinational, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of MP-376 (Levofloxacin Inhalation Solution; Aeroquin™) In Stable Cystic Fibrosis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2010-08-12
Enrollment: 330
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. Decreased efficacy, intolerance and high treatment burden with currently available therapies indicate a need for additional therapies. MP-376 (Aeroquin™) is a novel formulation of the fluoroquinolone levofloxacin that has been optimized for aerosol delivery. Preclinical and clinical studies conducted to date show that aerosol doses of MP-376 are safe and well tolerated, exert an antimicrobial effect, improve lung function and reduce the need for other anti-pseudomonal antibiotics. High concentrations of levofloxacin in the lung delivered as MP-376 are active against CF pathogens including those with high minimum inhibitory concentration (MIC) levels to aminoglycosides such as tobramycin (TOBI®) and other inhaled antimicrobial agents. Inhaled MP-376 can be delivered rapidly and efficiently using a customized PARI investigational configuration of the eFlow® nebulizer system.

Detailed description: This trial will be a double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin administered as MP-376 given for 28 days by the aerosol route to CF patients.

Study with completed results acquired from Horizon in 2024.

Eligibility criteria: Inclusion Criteria (selected):

* \>/= 12 years of age
* Confirmed Diagnosis of Cystic Fibrosis
* Positive sputum culture for P. aeruginosa at screening and within the past 12 months
* Patients are able to elicit an 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 28 days
* Able to reproducibly produce sputum and perform spirometry

Exclusion Criteria (selected):

* Use of any nebulized or systemic antibiotics within 28 days prior to baseline
* History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
* Evidence of respiratory infections within 14 days prior to dosing
* CrCl \< 20ml/min or \< 20ml/min/1.73 m2 at Screening

Primary outcomes:
measure: Time to an Exacerbation
timeFrame: Baseline to end of study (up to 59 days)
Secondary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in One Second (FEV1)
timeFrame: Baseline, day 28
measure: Change From Baseline in Pseudomonas Aeruginosa Sputum Density
timeFrame: Baseline, Day 28
measure: Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)
timeFrame: Baseline, Day 28
measure: Relative Change From Baseline in Percent Predicted FEV1
timeFrame: Baseline, Day 28
measure: Time to Administration of Other Systemic and/or Inhaled Antipseudomonal Antimicrobials
timeFrame: Baseline to end of study (up to 59 days)
measure: Time to First Hospitalization
timeFrame: Baseline to end of study (up to 59 days)
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From start of study until end of study (Up to 59 days)
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Anchorage
country: United States
state: Alaska
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital
state: California
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: Orange
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Wilmington
country: United States
state: Delaware
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Glenview
country: United States
state: Illinois
city: Niles
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Portland
country: United States
state: Maine
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Columbia
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Lebanon
country: United States
state: New Hampshire
city: Manchester
country: United States
state: New Hampshire
city: Livingston
country: United States
state: New Jersey
city: Long Branch
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Albany
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Colchester
country: United States
state: Vermont
city: Charlottesville
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Portsmouth
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Chilren's Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Miscericordiae Hospital
state: Queensland
city: Brisbane
country: Australia
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Center
city: New South Wales
country: Australia
facility: John Hunter Hospital
city: Hamilton
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center Mount Scopus
city: Petah Tikva
country: Israel
facility: Schneider Childrens Medical Center of Israel
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center
city: Auckland
country: New Zealand
facility: Auckland Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: