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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Amgen
- Enrollment
- 330
- Locations
- 14
- Primary Endpoint
- Time to an Exacerbation
Study Overview
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.
Detailed 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.
Study with completed results acquired from Horizon in 2024.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Aeroquin 240 mg
Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.
Intervention: Aeroquin (Drug)
Placebo
Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time to an Exacerbation
Time Frame: Baseline to end of study (up to 59 days)
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.
Secondary Outcomes
- Time to Administration of Other Systemic and/or Inhaled Antipseudomonal Antimicrobials(Baseline to end of study (up to 59 days))
- 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)
- Relative Change From Baseline in Percent Predicted FEV1(Baseline, Day 28)
- Time to First Hospitalization(Baseline to end of study (up to 59 days))
- Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)(Baseline, Day 28)
- Number of Participants With Treatment Emergent Adverse Events(From start of study until end of study (Up to 59 days))