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

NCT01270347 | Completed Phase 3 Results DMC

• 2 other identifiers: Mpex-2092010-019634-26
• Study Type: interventional
• Target: 282
• Locations: 6 countries
• Sites: 130

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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 the study (up to 168 days)

• Relative Change From Baseline 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 (SE) were determined from an analysis of covariance model with terms for treatment, region (US, non-US), and age (12 to 18 years, \> 18 years), and Baseline FEV1 (\< 55%, . 55%).

  Baseline, day 28

Secondary Outcomes (8)

• Percent Change From Baseline in Average Expired Flow Over the Middle Half of The FVC Maneuver (FEF25-75)

  Baseline, day 28

• Percent Change From Baseline in Forced Vital Capacity (FVC)

  Baseline, day 28

• Number of Participants in Each Category of Relative Change in Percent Predicted FEV1

  Day 28

• Number of Participants in Each Category of Percent Change From Baseline in FEV1

  Day 28

• Change From Baseline in Pseudomonas Aeruginosa Sputum Density

  Baseline, day 28

Study Arms (2)

Aeroquin

EXPERIMENTAL

Aeroquin, Inhaled Levofloxacin (MP-376)

Drug: MP-376 (Levofloxacin Solution for Inhalation)

TIS

ACTIVE COMPARATOR

Tobramycin Inhalation solution (TIS) \[TOBI® Novartis Pharmaceuticals\]

Drug: TIS (Tobramycin Inhalation Solution)

Interventions

MP-376 (Levofloxacin Solution for Inhalation) DRUG

MP-376 (Aeroquin, Levofloxacin solution for Inhalation) 240 mg administered BID for 28-days treatment followed by 28 days off treatment

Also known as: (Aeroquin, Levofloxacin solution for Inhalation)

Aeroquin

TIS (Tobramycin Inhalation Solution) DRUG

Tobramycin Inhalation Solution administered BID over 3 consecutive cycles of 28-days treatment followed by 28 days off treatment

Also known as: TOBI

TIS

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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Forest Laboratories: collaborator

Study Sites (130)

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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Little Rock, Arkansas, 72202, 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 Diego, California, 92123, United States

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San Francisco, California, 94115, 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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New Haven, Connecticut, 65020, United States

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Wilmington, Delaware, 19803, United States

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Gainesville, Florida, 32610, 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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Peoria, Illinois, 61637, United States

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Indianapolis, Indiana, 43202, 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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Portland, Maine, 04102, United States

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Baltimore, Maryland, 21287, 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, 63110, United States

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Omaha, Nebraska, 68105, 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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Morristown, New Jersey, 07962, United States

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Albuquerque, New Mexico, 87131, United States

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Albany Medical College #2

Albany, New York, 12208, United States

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Albany, New York, 12208, United States

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New Hyde Park, New York, 11042, United States

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New York, New York, 10003, 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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Durham, North Carolina, 27710, 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 CF Center

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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Morgantown, West Virginia, 26506, United States

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Milwaukee, Wisconsin, 53201, United States

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Unknown Facility

Milwaukee, Wisconsin, 53266, United States

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Hôpital Pellegrin Enfants - CHU Bordeaux

Bordeaux, 33076, France

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CRCM adultes et enfants Service des maladies respiratoires et pédiatrie 1 CHU- Arnaud de Villeneuve

Montpellier, 34295, France

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Hôpital Cochin

Paris, 75014, France

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Hôpital Necker-Enfants Malades

Paris, 75743, France

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Hôpital Haut-Lévêque CHU de Bordeaux

Pessac, 33604, France

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CRCM adulte Hôpital Larrey-CHU de Toulouse

Toulouse, 31059, France

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Charité Campus Virchow-Klinikum

Berlin, Germany

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Universitätskinderklinik Dresden Mukoviszidose-Ambulanz

Dresden, Germany

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Universitätsklinikum Essen

Essen, Germany

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Katharina-Kasper Kliniken GmbH St. Elisabethen-Krankenhaus Medizinische Klinik

Frankfurt, Germany

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Universitätsklinikum Frankfurt

Frankfurt, Germany

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Universitätsklinik Gießen und Marburg GmbH Zentrum für Kinderheilkunde und Jugendmedizin

Gieben, Germany

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Kinderärztliche Gemeinschaftspraxis Dr. H. E. Heuer, Dr. C. Runge, W. Sextro

Hamburg, Germany

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Universitätsklinikum Kiel

Kiel, Germany

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Dr. von Haunersches Kinderspital der Universität München Christiane Herzog Ambulanz

Munich, Germany

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Ludwig-Maximilians Universität Klinikum Innenstadt

München, Germany

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Universitätsklinik für Kinder- und Jugendmedizin

Tübingen, Germany

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Cork University Hospital

Cork, Ireland

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Beaumont Hospital

Dublin, Ireland

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National Children's Hospital Tallaght

Dublin, Ireland

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St. Vincent's University Hospital

Dublin, Ireland

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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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Safra Childrens Hospital, Sheba Medical Center

Ramat Gan, 52621, Israel

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Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

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Birmingham Heartlands Hospital

Birmingham, B95SS, United Kingdom

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Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

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St James's University Hospital

Leeds, LS97TF, United Kingdom

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King's College Hospital

London, SE59RS, United Kingdom

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University Hospital Llandough, Penarth

Penarth, CF64 2XX, United Kingdom

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Related Publications (1)

• 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.

  PMID: 26935334 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Inhalation

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

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2011
• First Posted: January 5, 2011
• Study Start: January 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: June 1, 2013
• Last Updated: December 13, 2024
• Results First Posted: May 21, 2024

Record last verified: 2024-11

Locations

IE (4); FR (6); GB (6); US (99); DE (11); IL (4)