Clinical trial NCT01270347: Trial of Aeroquin Versus Tobramycin Inhalation Solution (TIS) in Cystic Fibrosis (CF) Patients
Official title: Phase 3, Open-label, Randomized Trial to Evaluate the Safety and Efficacy of MP-376 Inhalation Solution (Aeroquin) vs. Tobramycin Inhalation Solution (TIS) in Stable CF Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2011-01-05
Enrollment: 282
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. 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 study will assess the comparative safety of MP-376 (Aeroquin) and Tobramycin Inhalation solution (TIS) \[TOBI® Novartis Pharmaceuticals\] over three consecutive cycles of 28-days treatment followed by 28-days off in stable CF patients with chronic P. aeruginosa lung infection. Efficacy data for MP-376 and TIS at the end of the first 28-day treatment period will also be compared, as well as explored over multiple treatment cycles.

Study patients participating in Mpex 209 will be given the option to participate in a six-month open label extension phase of the Mpex 209 protocol. The open label extension will allow enrolled patients to receive three additional courses of MP-376 (levofloxacin inhalation solution, Aeroquin™).

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 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 tobramycin 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 inhaled or systemic aminoglycosides including tobramycin or any excipients
* Evidence of acute upper within 10 days or lower respiratory infections within 28 days prior to dosing
* CrCl \< 20 at Screening
* History of lung transplantation

Extension Portion of the Study: Patients enrolled in Mpex 209 are permitted to participate in the open label extension as long as they complete Visit 7 (Day 168), provide informed consent for participation in the open label extension of in the study and are clinically stable, as assessed by the Investigator.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From start of study until end of the study (up to 168 days)
measure: Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (FEV1)
timeFrame: Baseline, day 28
Secondary outcomes:
measure: Percent Change From Baseline in Average Expired Flow Over the Middle Half of The FVC Maneuver (FEF25-75)
timeFrame: Baseline, day 28
measure: Percent Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: Baseline, day 28
measure: Number of Participants in Each Category of Relative Change in Percent Predicted FEV1
timeFrame: Day 28
measure: Number of Participants in Each Category of Percent Change From Baseline in FEV1
timeFrame: Day 28
measure: Change From Baseline in Pseudomonas Aeruginosa Sputum Density
timeFrame: Baseline, day 28
measure: Number of Participants in Each Category of 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: Number of Participants in Each Category of Change From Baseline in the Respiratory Domain of CFQ-R
timeFrame: Baseline, day 28
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: Little Rock
country: United States
state: Arkansas
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 Diego
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: New Haven
country: United States
state: Connecticut
city: Wilmington
country: United States
state: Delaware
city: Gainesville
country: United States
state: Florida
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: Peoria
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
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: Portland
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
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: 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: Morristown
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College #2
state: New York
city: Albany
country: United States
state: New York
city: New Hyde Park
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: Durham
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
facility: Oklahoma CF Center
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: Morgantown
country: United States
state: West Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Bordeaux
country: France
facility: Hôpital Pellegrin Enfants - CHU Bordeaux
city: Montpellier
country: France
facility: CRCM adultes et enfants Service des maladies respiratoires et pédiatrie 1 CHU- Arnaud de Villeneuve
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Pessac
country: France
facility: Hôpital Haut-Lévêque CHU de Bordeaux
city: Toulouse
country: France
facility: CRCM adulte Hôpital Larrey-CHU de Toulouse
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Dresden
country: Germany
facility: Universitätskinderklinik Dresden Mukoviszidose-Ambulanz
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Katharina-Kasper Kliniken GmbH St. Elisabethen-Krankenhaus Medizinische Klinik
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Gieben
country: Germany
facility: Universitätsklinik Gießen und Marburg GmbH Zentrum für Kinderheilkunde und Jugendmedizin
city: Hamburg
country: Germany
facility: Kinderärztliche Gemeinschaftspraxis Dr. H. E. Heuer, Dr. C. Runge, W. Sextro
city: Kiel
country: Germany
facility: Universitätsklinikum Kiel
city: Munchen
country: Germany
facility: Ludwig-Maximilians Universität Klinikum Innenstadt
city: Munich
country: Germany
facility: Dr. von Haunersches Kinderspital der Universität München Christiane Herzog Ambulanz
city: Tubingen
country: Germany
facility: Universitätsklinik für Kinder- und Jugendmedizin
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: National Children's Hospital Tallaght
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
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: Safra Childrens Hospital, Sheba Medical Center
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Penarth
country: United Kingdom
facility: University Hospital Llandough, Penarth
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Elborn JS, Flume PA, Cohen F, Loutit J, VanDevanter DR. Safety and efficacy of prolonged levofloxacin inhalation solution (APT-1026) treatment for cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. J Cyst Fibros. 2016 Sep;15(5):634-40. doi: 10.1016/j.jcf.2016.01.005. Epub 2016 Feb 28.