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

Cystic Fibrosis Clinical Trial

— TIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01270347
• Other study ID #: Mpex-209
• Secondary ID: 2010-019634-26
• Status: Completed
• Phase: Phase 3
• Start date: January 2011
• Est. completion date: June 2013

Study information

• Verified date: April 2024
• Source: Horizon Pharma USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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™).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: June 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
France	Hôpital Pellegrin Enfants - CHU Bordeaux	Bordeaux
France	CRCM adultes et enfants Service des maladies respiratoires et pédiatrie 1 CHU- Arnaud de Villeneuve	Montpellier
France	Hôpital Cochin	Paris
France	Hôpital Necker-Enfants Malades	Paris
France	Hôpital Haut-Lévêque CHU de Bordeaux	Pessac
France	CRCM adulte Hôpital Larrey-CHU de Toulouse	Toulouse
Germany	Charité Campus Virchow-Klinikum	Berlin
Germany	Universitätskinderklinik Dresden Mukoviszidose-Ambulanz	Dresden
Germany	Universitätsklinikum Essen	Essen
Germany	Katharina-Kasper Kliniken GmbH St. Elisabethen-Krankenhaus Medizinische Klinik	Frankfurt
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinik Gießen und Marburg GmbH Zentrum für Kinderheilkunde und Jugendmedizin	Gieben
Germany	Kinderärztliche Gemeinschaftspraxis Dr. H. E. Heuer, Dr. C. Runge, W. Sextro	Hamburg
Germany	Universitätsklinikum Kiel	Kiel
Germany	Ludwig-Maximilians Universität Klinikum Innenstadt	Munchen
Germany	Dr. von Haunersches Kinderspital der Universität München Christiane Herzog Ambulanz	Munich
Germany	Universitätsklinik für Kinder- und Jugendmedizin	Tubingen
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	National Children's Hospital Tallaght	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center Mount Scopus	Jerusalem
Israel	Schneider Childrens Medical Center of Israel	Petah Tikva
Israel	Safra Childrens Hospital, Sheba Medical Center	Ramat Gan
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	St James's University Hospital	Leeds
United Kingdom	King's College Hospital	London
United Kingdom	University Hospital Llandough, Penarth	Penarth
United States	Albany Medical College #2	Albany	New York
United States	Childrens Hospital	Los Angeles	California
United States	Oklahoma CF Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Horizon Pharma USA, Inc.	Forest Laboratories

Countries where clinical trial is conducted

United States,  France,  Germany,  Ireland,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Percent Change From Baseline in Average Expired Flow Over the Middle Half of The FVC Maneuver (FEF25-75)	LSMean and SE were determined from an ANCOVA model with terms for treatment, region (US, non-US), age (12-18 years, >18 years), baseline FEV1 (<55%, >=55%), and baseline as a covariate.	Baseline, day 28
Secondary	Percent Change From Baseline in Forced Vital Capacity (FVC)	LSMean and SE were determined from an ANCOVA model with terms for treatment, region (US, non-US), age (12-18 years, >18 years), baseline FEV1 (<55%, >=55%), and baseline as a covariate	Baseline, day 28
Secondary	Number of Participants in Each Category of Relative Change in Percent Predicted FEV1	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer.	Day 28
Secondary	Number of Participants in Each Category of Percent Change From Baseline in FEV1	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer.	Day 28
Secondary	Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Pseudomonas aeruginosa density was measured as log10 colony-forming units [CFU] per gram sputum.	Baseline, day 28
Secondary	Number of Participants in Each Category of Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Pseudomonas aeruginosa density was measured as log10 colony-forming units [CFU] per gram sputum.	Baseline, day 28
Secondary	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.	Baseline, day 28
Secondary	Number of Participants in Each Category of Change From Baseline in the Respiratory Domain of 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.	Baseline, day 28