A Phase 2 Study of MP-376 to Prevent Acute Exacerbations in Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from frequent and recurrent acute exacerbations (AECB) which are associated with enormous healthcare expenditures and significant morbidity, specifically an increased risk of death, a decline in pulmonary function and a significant change in quality of life. Bacteria appear to have an important role in acute exacerbations in chronic bronchitis and COPD. Studies of acute exacerbations in COPD have shown a reduction in bacterial load with prolonged exacerbation-free interval. In addition, recent studies indicate that acquisition of a new strain of H. influenzae, M. catarrhalis, S. pneumoniae or P. aeruginosa are responsible for many of these exacerbations. Chronic inflammation and bacterial infection predispose many patients to frequent and recurrent acute exacerbations. Mpex believes that intermittent administration of inhaled MP-376 in high risk patients will decrease the incidence of acute exacerbations by both by lowering the organism burden, and resultant inflammation, as well as pre-emptive eradication of any newly acquired bacterial strains.

Detailed Description
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This study will be a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of MP-376 inhalation solution given daily for 5 days in a 28 day treatment cycle to COPD patients.

Official Title
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Phase 2, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability and Efficacy of MP-376 Inhalation Solution Administered for 5 Days Every 28 Days to Prevent Acute Exacerbations in High Risk COPD Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: MP-376
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (selected): > 40 years of age History of COPD Forced expiratory volume in 1 second (FEV1) </= 70% of predicted and FEV1/Forced vital capacity (FVC) </= 0.7 value at screening Have at least two acute exacerbation episodes in the proceeding year Clinically stable with no changes in health status within the last 30 days Lifetime smoking history of at least 10 pack-years Willing and able to use a daily electronic diary Exclusion Criteria (selected): Use of any systemic or inhaled antibiotics within 30 days prior to baseline History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication Creatinine clearance < 40 mg/ml/min, AST, ALT >/= 5 x upper limit of normal (ULN) or total bilirubin >/= 3 x ULN at Screening

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo inhaled twice daily via the PARI eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles | Drug: Placebo<br>* same frequency as study drug using the same method of delivery<br>* Other names: MP-376 color-matched placebo;|
| Experimental: MP-376 240 mg Twice Daily (BID)<br>MP-376 240 mg BID inhaled via the PARI eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles | Drug: MP-376<br>* MP-376 administered via inhalation for 5 consecutive days within 28-day treatment cycles for up to 12 cycles<br>* Other names: Aeroquin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exacerbation Rate | The number of acute exacerbations per patient-year of study participation, where an acute exacerbation was defined as a deterioration in respiratory symptoms that required treatment with antibiotics, corticosteroids, hospitalization or a combination of those treatments. | From randomization to the patients final study visit (up to 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Acute Exacerbation | From the beginning of antibiotics and/or systemic corticosteroids to the end of antibiotics and/or systemic corticosteroids, whichever was longer, for treatment of the first acute exacerbation | from randomization to the patient's final study visit (up to 12 months) | 
| Percent Change in Forced Vital Capacity (FVC) | The percent change in the amount of air a patient can inhale | from baseline to the conclusion of the fourth 28-day treatment cycle (4 months) | 
| Percent Change in Forced Expiratory Volume in 1 Second (FEV1) | The percent change in the amount of air a patient can exhale in 1 second | from baseline to the conclusion of the fourth 28-day treatment cycle (4 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Patients