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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01180634
• Other study ID #: Mpex-207
• Secondary ID: 2010-019515-38
• Status: Completed
• Phase: Phase 3
• Start date: November 4, 2010
• Est. completion date: May 7, 2012

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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: May 7, 2012
• Est. primary completion date: May 7, 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 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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Aeroquin
Inhalation Solution
• Placebo
Inhalation Solution

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Mater Miscericordiae Hospital	Brisbane	Queensland
Australia	Monash Medical Center	Melbourne
Australia	Royal Children's Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New South Wales
Australia	Westmead Chilren's Hospital	Westmead	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center Mount Scopus	Jerusalem
Israel	Schneider Childrens Medical Center of Israel	Petah Tikva
Israel	Sheba Medical Center	Ramat-Gan
New Zealand	Auckland Hospital	Auckland
United States	Childrens Hospital	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Horizon Pharma USA, Inc.	Forest Laboratories

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
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. 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
Secondary	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
Secondary	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)
Secondary	Time to First Hospitalization	Median and 95%CI was estimated using Kaplan Meier estimates.	Baseline to end of study (up to 59 days)
Secondary	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)