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: Placebo; Drug: Aeroquin

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.

• 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

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
Experimental: Aeroquin 240 mg; Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Drug: Aeroquin; Inhalation Solution; Other Names: MP-376, Levofloxacin Inhalation solution 240 mg
Placebo Comparator: Placebo; Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.	Drug: Placebo; Inhalation Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to an Exacerbation	The start of the exacerbation was determined by the earliest date at which a participant concurrently met at least 4 of the 12 modified Fuchs symptoms/signs; discontinued from the study early; died; or received an antipseudomonal agent for an event that did not meet modified Fuchs criteria but was determined to be an exacerbation by the Blinded Exacerbation. Fuchs symptoms/signs; Change in sputum; New or increased hemoptysis; Increased cough; Increased dyspnea; Malaise, fatigue or lethargy; Temperature above 38oC; Anorexia or weight loss; Sinus pain or tenderness; Change in sinus discharge; Change in physical examination of the chest; Decrease in pulmonary function by 10 percent or more from a previously recorded value; Radiographic changes indicative of pulmonary infection Median and 95%Ci were estimated using Kaplan Meier estimates.	Baseline to end of study (up to 59 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Percent Predicted Forced Expiratory Volume in One Second (FEV1)	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12-18 years, >18 years), and baseline FEV1 (<55%, >=55%).	Baseline, day 28
Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Pseudomonas aeruginosa density was measured as log10 colony-forming units [CFU] per gram sputum. LSMean and standard are determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12-18 years, >18 years), baseline FEV1 (<55%, >=55%), and baseline organism log density.	Baseline, Day 28
Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)	The Cystic Fibrosis Questionnaire (CFQ-R) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. LSMean and standard error were determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12 to 18 years, > 18 years), Baseline FEV1 (<55%, ≥ 55%), and Baseline value.	Baseline, Day 28
Relative Change From Baseline in Percent Predicted FEV1	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12-18 years, >18 years), and baseline FEV1 (<55%, >=55%).	Baseline, Day 28
Time to Administration of Other Systemic and/or Inhaled Antipseudomonal Antimicrobials	Participants who had at least one of four worsening respiratory symptoms (increased cough, increased sputum/chest congestion, decreased exercise tolerance, decreased appetite) at the time of administration of the anti-pseudomonal antimicrobial agent were included in the analysis. Median and 95% CI are estimated using Kaplan Meier estimates.	Baseline to end of study (up to 59 days)
Time to First Hospitalization	Median and 95%CI was estimated using Kaplan Meier estimates.	Baseline to end of study (up to 59 days)
Number of Participants With Treatment Emergent Adverse Events	An AE was defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a Study Drug, whether or not considered related to the Study Drug. An AE could potentially be a new disease, any untoward event, or an exacerbation of a pre-existing condition. AEs included, but were not limited to: Any symptom not previously reported by the patient (medical history); An exacerbation of a pre-existing illness; An increase in frequency or intensity of a pre-existing episodic event or condition; A condition first detected or diagnosed after Study Drug administration even though the condition may have been present before the start of the study; Overdose of Study Drug	From start of study until end of study (Up to 59 days)

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: Forest Laboratories
• Investigators: Study Director: MD, Amgen

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2010
• Primary Completion (Actual): May 7, 2012
• Study Completion (Actual): May 7, 2012

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Levofloxacin
• Other Study ID Numbers: Mpex-207; 2010-019515-38 (EudraCT Number)