MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Monash Medical Center
  • New South Wales, Australia
    • John Hunter Hospital
  • New South Wales
    • Westmead, New South Wales, Australia
      • Westmead Hospital
    • Westmead, New South Wales, Australia
      • Westmead Chilren's Hospital
  • Queensland
    • Brisbane, Queensland, Australia
    • Brisbane, Queensland, Australia
      • Mater Miscericordiae Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia
      • The Alfred Hospital
    • Melbourne, Victoria, Australia
      • Royal Children's Hospital
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N3Z5
    • Kingston, Ontario, Canada, K7L5G2
    • Ottawa, Ontario, Canada, K1H8L6
• 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, 52620
    • Sheba Medical Center
• New Zealand
  • Auckland, New Zealand
    • Auckland Hospital
• 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
  • 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 Francisco, California, United States, 94115
    • San Francisco, California, United States, 94143
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Denver, Colorado, United States, 80206
  • Connecticut
    • Hartford, Connecticut, United States, 06106
  • Delaware
    • Wilmington, Delaware, United States, 19803
  • Florida
    • 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
  • Indiana
    • Indianapolis, Indiana, United States, 46202
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Lexington, Kentucky, United States, 40536
    • Louisville, Kentucky, United States, 40202
  • Louisiana
    • New Orleans, Louisiana, United States, 70011
  • Maine
    • Portland, Maine, United States, 04102
  • 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
    • Saint Louis, Missouri, United States, 63104
  • Nebraska
    • Omaha, Nebraska, United States, 68198
  • 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
    • Long Branch, New Jersey, United States, 07440
    • Morristown, New Jersey, United States, 07962
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • New York
    • Albany, New York, United States, 12208
    • New York, New York, United States, 10032
    • New York, New York, United States, 10011
    • New York, New York, United States, 10003
    • Syracuse, New York, United States, 13210
    • Valhalla, New York, United States, 10595
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
  • 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
  • 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
    • Seattle, Washington, United States, 98195
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: Placebo; same volume and frequency as study drug
Experimental: 1; Inhaled MP-376 (Aeroquin)	Drug: MP-376 (Levofloxacin solution for Inhalation); 240 mg of MP-376 administered BID for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to an exacerbation	56 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to administration of other anti-pseudomonal antimicrobials	56 days
Evaluate changes in FEV1, FEF 25-75 and FVC from baseline to end of treatment	28 days
Changes in bacterial load and susceptibility patterns of isolated organisms from baseline to end of treatment	28 days
Changes in respiratory domain of CFQ-R from baseline to end of treatment baseline to end of treatment	28 days
Evaluate the safety of MP-376 administered over 28 days, compared to placebo	56 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 10, 2010
• First Submitted That Met QC Criteria: August 10, 2010
• First Posted (Estimate): August 12, 2010

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; Levofloxacin; Ofloxacin
• Other Study ID Numbers: Mpex-207; 2010-019515-38 (EudraCT Number)