Trial of Aeroquin Versus Tobramycin Inhalation Solution (TIS) in Cystic Fibrosis (CF) Patients (TIS)

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: MP-376 (Levofloxacin Solution for Inhalation); Drug: TIS (Tobramycin Inhalation Solution)

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 Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Hôpital Pellegrin Enfants - CHU Bordeaux
  • Montpellier, France, 34295
    • CRCM adultes et enfants Service des maladies respiratoires et pédiatrie 1 CHU- Arnaud de Villeneuve
  • Paris, France, 75014
    • Hopital Cochin
  • Paris, France, 75743
    • Hôpital Necker-Enfants Malades
  • Pessac, France, 33604
    • Hôpital Haut-Lévêque CHU de Bordeaux
  • Toulouse, France, 31059
    • CRCM adulte Hôpital Larrey-CHU de Toulouse
• Germany
  • Berlin, Germany
    • Charité Campus Virchow-Klinikum
  • Dresden, Germany
    • Universitätskinderklinik Dresden Mukoviszidose-Ambulanz
  • Essen, Germany
    • Universitatsklinikum Essen
  • Frankfurt, Germany
    • Universitatsklinikum Frankfurt
  • Frankfurt, Germany
    • Katharina-Kasper Kliniken GmbH St. Elisabethen-Krankenhaus Medizinische Klinik
  • Gieben, Germany
    • Universitätsklinik Gießen und Marburg GmbH Zentrum für Kinderheilkunde und Jugendmedizin
  • Hamburg, Germany
    • Kinderärztliche Gemeinschaftspraxis Dr. H. E. Heuer, Dr. C. Runge, W. Sextro
  • Kiel, Germany
    • Universitätsklinikum Kiel
  • Munchen, Germany
    • Ludwig-Maximilians Universität Klinikum Innenstadt
  • Munich, Germany
    • Dr. von Haunersches Kinderspital der Universität München Christiane Herzog Ambulanz
  • Tubingen, Germany
    • Universitätsklinik für Kinder- und Jugendmedizin
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • St. Vincent's University Hospital
  • Dublin, Ireland
    • National Children's Hospital Tallaght
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Jerusalem, Israel, 91240
    • Hadassah Medical Center Mount Scopus
  • Petah Tikva, Israel, 49202
    • Schneider Childrens Medical Center of Israel
  • Ramat Gan, Israel, 52621
    • Safra Childrens Hospital, Sheba Medical Center
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • Birmingham, United Kingdom, B95SS
    • Birmingham Heartlands Hospital
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital
  • Leeds, United Kingdom, LS97TF
    • St James's University Hospital
  • London, United Kingdom, SE59RS
    • King's College Hospital
  • Penarth, United Kingdom, CF64 2XX
    • University Hospital Llandough, Penarth
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
  • Alaska
    • Anchorage, Alaska, United States, 99508
  • Arizona
    • Phoenix, Arizona, United States, 85016
    • Tucson, Arizona, United States, 85724
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
  • California
    • La Jolla, California, United States, 92037
    • Long Beach, California, United States, 90806
    • Los Angeles, California, United States, 90033
    • Los Angeles, California, United States, 90027
      • Childrens Hospital
    • Oakland, California, United States, 94611
    • Orange, California, United States, 92868
    • Palo Alto, California, United States, 94304
    • Sacramento, California, United States, 95817
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92123
    • San Francisco, California, United States, 94115
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Denver, Colorado, United States, 80206
  • Connecticut
    • Hartford, Connecticut, United States, 06106
    • New Haven, Connecticut, United States, 65020
  • Delaware
    • Wilmington, Delaware, United States, 19803
  • Florida
    • Gainesville, Florida, United States, 32610
    • Jacksonville, Florida, United States, 32207
    • Miami, Florida, United States, 33136
    • Orlando, Florida, United States, 32801
    • Saint Petersburg, Florida, United States, 33701
    • Tampa, Florida, United States, 33606
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Idaho
    • Boise, Idaho, United States, 83712
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Chicago, Illinois, United States, 60614
    • Glenview, Illinois, United States, 60025
    • Niles, Illinois, United States, 60714
    • Peoria, Illinois, United States, 61637
  • Indiana
    • Indianapolis, Indiana, United States, 46202
    • Indianapolis, Indiana, United States, 43202
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Lexington, Kentucky, United States, 40536
    • Louisville, Kentucky, United States, 40202
  • Maine
    • Portland, Maine, United States, 04102
  • Maryland
    • Baltimore, Maryland, United States, 21287
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
    • Boston, Massachusetts, United States, 02115
    • Worcester, Massachusetts, United States, 01655
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
    • Detroit, Michigan, United States, 48201
    • Grand Rapids, Michigan, United States, 49503
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
  • Mississippi
    • Jackson, Mississippi, United States, 39216
  • Missouri
    • Columbia, Missouri, United States, 65212
    • Kansas City, Missouri, United States, 64108
    • Saint Louis, Missouri, United States, 63110
  • Nebraska
    • Omaha, Nebraska, United States, 68105
  • Nevada
    • Las Vegas, Nevada, United States, 89107
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
    • Manchester, New Hampshire, United States, 03104
  • New Jersey
    • Livingston, New Jersey, United States, 07039
    • Morristown, New Jersey, United States, 07962
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • New York
    • Albany, New York, United States, 12208
    • Albany, New York, United States, 12208
      • Albany Medical College #2
    • New Hyde Park, New York, United States, 11042
    • New York, New York, United States, 10032
    • New York, New York, United States, 10003
    • Syracuse, New York, United States, 13210
    • Valhalla, New York, United States, 10595
  • North Carolina
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Akron, Ohio, United States, 44308
    • Cincinnati, Ohio, United States, 45229
    • Columbus, Ohio, United States, 43205
    • Dayton, Ohio, United States, 45404
    • Toledo, Ohio, United States, 43606
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma CF Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19102
    • Pittsburgh, Pennsylvania, United States, 15224
  • South Carolina
    • Charleston, South Carolina, United States, 29425
    • Columbia, South Carolina, United States, 29203
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
  • Tennessee
    • Memphis, Tennessee, United States, 38105
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Austin, Texas, United States, 78723
    • Dallas, Texas, United States, 75390
    • Fort Worth, Texas, United States, 76104
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78212
    • Tyler, Texas, United States, 75708
  • Utah
    • Salt Lake City, Utah, United States, 84132
  • Vermont
    • Colchester, Vermont, United States, 05446
  • Virginia
    • Charlottesville, Virginia, United States, 22908
    • Norfolk, Virginia, United States, 23507
    • Portsmouth, Virginia, United States, 23708
    • Richmond, Virginia, United States, 23298
  • Washington
    • Seattle, Washington, United States, 98105
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
    • Milwaukee, Wisconsin, United States, 53266

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aeroquin; Aeroquin, Inhaled Levofloxacin (MP-376)	Drug: MP-376 (Levofloxacin Solution for Inhalation); MP-376 (Aeroquin, Levofloxacin solution for Inhalation) 240 mg administered BID for 28-days treatment followed by 28 days off treatment; Other Names: (Aeroquin, Levofloxacin solution for Inhalation)
ACTIVE_COMPARATOR: TIS; Tobramycin Inhalation solution (TIS) [TOBI® Novartis Pharmaceuticals]	Drug: TIS (Tobramycin Inhalation Solution); Tobramycin Inhalation Solution administered BID over 3 consecutive cycles of 28-days treatment followed by 28 days off treatment; Other Names: TOBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Assessment of adverse events and safety from Baseline through Final Visit Extension portion of Study: Descriptive statistics for all patients receiving at least one dose of MP-376 in the extension phase of the study will be summarized for the safety, microbiology, and disease-related endpoints. No formal hypothesis tests are planned.	168 and 336 days
Efficacy	Percent change in percent predicted FEV1 from Baseline to Day 28	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in respiratory and other domains of CFQ-R from Baseline to Day 28	28 days
Evaluate changes in FEV1 and FVC from Baseline to Day 28	28 days
Changes in bacterial load and susceptability patterns of isolated organisms from Baseline to Day 28	28 days

Collaborators and Investigators

• Sponsor: Horizon Pharma USA, Inc.
• Collaborators: Forest Laboratories

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: January 4, 2011
• First Posted (ESTIMATE): January 5, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2018
• Last Update Submitted That Met QC Criteria: January 17, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Pharmaceutical Solutions; Levofloxacin; Ofloxacin; Tobramycin
• Other Study ID Numbers: Mpex-209; 2010-019634-26 (EUDRACT_NUMBER)