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

NCT01180634 | Completed Phase 3 Results DMC

• 2 other identifiers: Mpex-2072010-019515-38
• Study Type: interventional
• Target: 330
• Locations: 5 countries
• Sites: 112

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Absolute Change in Percent Predicted Forced Expiratory Volume in One Second (FEV1)

  Baseline, day 28

• Change From Baseline in Pseudomonas Aeruginosa Sputum Density

  Baseline, Day 28

• Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)

  Baseline, Day 28

• Relative Change From Baseline in Percent Predicted FEV1

  Baseline, Day 28

• Time to Administration of Other Systemic and/or Inhaled Antipseudomonal Antimicrobials

  Baseline to end of study (up to 59 days)

Study Arms (2)

Aeroquin 240 mg

EXPERIMENTAL

Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.

Drug: Aeroquin

Placebo

PLACEBO COMPARATOR

Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.

Drug: Placebo

Interventions

Aeroquin DRUG

Inhalation Solution

Also known as: MP-376, Levofloxacin Inhalation solution 240 mg

Aeroquin 240 mg

Placebo DRUG

Inhalation Solution

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \>/= 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead
• Forest Laboratories: collaborator

Study Sites (112)

Unknown Facility

Mobile, Alabama, 36608, United States

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Anchorage, Alaska, 99508, United States

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Phoenix, Arizona, 85016, United States

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Tucson, Arizona, 85724, United States

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La Jolla, California, 92037, United States

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Long Beach, California, 90806, United States

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Childrens Hospital

Los Angeles, California, 90027, United States

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Los Angeles, California, 90033, United States

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Oakland, California, 94611, United States

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Orange, California, 92868, United States

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Palo Alto, California, 94304, United States

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Sacramento, California, 95817, United States

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San Diego, California, 92103, United States

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San Francisco, California, 94115, United States

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San Francisco, California, 94143, United States

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Aurora, Colorado, 80045, United States

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Denver, Colorado, 80206, United States

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Hartford, Connecticut, 06106, United States

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Wilmington, Delaware, 19803, United States

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Jacksonville, Florida, 32207, United States

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Miami, Florida, 33136, United States

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Orlando, Florida, 32801, United States

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St. Petersburg, Florida, 33701, United States

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Tampa, Florida, 33606, United States

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Atlanta, Georgia, 30322, United States

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Boise, Idaho, 83712, United States

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Chicago, Illinois, 60614, United States

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Chicago, Illinois, 60637, United States

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Glenview, Illinois, 60025, United States

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Niles, Illinois, 60714, United States

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Indianapolis, Indiana, 46202, United States

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Wichita, Kansas, 67214, United States

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Lexington, Kentucky, 40536, United States

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Louisville, Kentucky, 40202, United States

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New Orleans, Louisiana, 70011, United States

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Portland, Maine, 04102, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Worcester, Massachusetts, 01655, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48201, United States

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Grand Rapids, Michigan, 49503, United States

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Minneapolis, Minnesota, 55455, United States

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Jackson, Mississippi, 39216, United States

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Columbia, Missouri, 65212, United States

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Kansas City, Missouri, 64108, United States

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St Louis, Missouri, 63104, United States

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St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68198, United States

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Las Vegas, Nevada, 89107, United States

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Lebanon, New Hampshire, 03756, United States

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Manchester, New Hampshire, 03104, United States

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Livingston, New Jersey, 07039, United States

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Long Branch, New Jersey, 07440, United States

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Morristown, New Jersey, 07962, United States

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Albuquerque, New Mexico, 87131, United States

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Albany, New York, 12208, United States

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New York, New York, 10003, United States

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New York, New York, 10011, United States

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New York, New York, 10032, United States

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Syracuse, New York, 13210, United States

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Valhalla, New York, 10595, United States

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Chapel Hill, North Carolina, 27599, United States

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Akron, Ohio, 44308, United States

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Cincinnati, Ohio, 45229, United States

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Columbus, Ohio, 43205, United States

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Dayton, Ohio, 45404, United States

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Toledo, Ohio, 43606, United States

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Oklahoma City, Oklahoma, 73104, United States

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Oklahoma City, Oklahoma, 73112, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19102, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Charleston, South Carolina, 29425, United States

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Columbia, South Carolina, 29203, United States

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Sioux Falls, South Dakota, 57117, United States

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Memphis, Tennessee, 38105, United States

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Nashville, Tennessee, 37232, United States

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Austin, Texas, 78723, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78212, United States

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Tyler, Texas, 75708, United States

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Salt Lake City, Utah, 84132, United States

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Colchester, Vermont, 05446, United States

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Charlottesville, Virginia, 22908, United States

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Norfolk, Virginia, 23507, United States

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Portsmouth, Virginia, 23708, United States

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Richmond, Virginia, 23298, United States

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Seattle, Washington, 98105, United States

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Seattle, Washington, 98195, United States

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Morgantown, West Virginia, 26506, United States

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Milwaukee, Wisconsin, 53201, United States

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John Hunter Hospital

New South Wales, New South Wales, Australia

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Westmead Chilren's Hospital

Westmead, New South Wales, Australia

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Westmead Hospital

Westmead, New South Wales, Australia

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Mater Miscericordiae Hospital

Brisbane, Queensland, Australia

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Unknown Facility

Brisbane, Queensland, Australia

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Royal Adelaide Hospital

Adelaide, South Australia, Australia

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Royal Children's Hospital

Melbourne, Victoria, Australia

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The Alfred Hospital

Melbourne, Victoria, Australia

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Monash Medical Center

Melbourne, Australia

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Unknown Facility

Hamilton, Ontario, L8N3Z5, Canada

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Kingston, Ontario, K7L5G2, Canada

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Ottawa, Ontario, K1H8L6, Canada

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Rambam Medical Center

Haifa, 31096, Israel

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Hadassah Medical Center Mount Scopus

Jerusalem, 91240, Israel

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Schneider Childrens Medical Center of Israel

Petah Tikva, 49202, Israel

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Sheba Medical Center

Ramat Gan, 52620, Israel

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Auckland Hospital

Auckland, New Zealand

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MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Horizon Pharma USA, Inc.

medicalinformation@horizontherapeutics.com

1-866-479-6742

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2010
• First Posted: August 12, 2010
• Study Start: November 4, 2010
• Primary Completion: May 7, 2012
• Study Completion: May 7, 2012
• Last Updated: December 18, 2024
• Results First Posted: April 30, 2024

Record last verified: 2024-12

Locations

US (95); AU (9); NZ (1); IL (4); CA (3)