Safety, Pharmacokinetic and Pharmacodynamic Study of MP-376 in Patients With Cystic Fibrosis

Phase I, Single and Multi-dose, Placebo Controlled, Randomized, Dose-Escalation Study to Evaluate the Safety, Tolerability and PK Profile of MP-376 Using the PARI eFlow Nebulizer for 14 Days to CF Patients

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 and reduce the emergence of resistant bacteria.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: MP-376 (Levofloxacin solution for Inhalation); Drug: placebo

Detailed Description

This trial will be a single-blind, placebo-controlled, dose escalating between cohorts, single and multi-dose, multi-center study to evaluate the safety, tolerability and pharmacokinetic profile of levofloxacin administered as MP-376 once, then twice daily for 14 days by the aerosol route to CF patients.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
    • Los Angeles, California, United States, 90033
    • Palo Alto, California, United States, 94303
  • Florida
    • Orlando, Florida, United States, 32801
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
  • Nebraska
    • Omaha, Nebraska, United States, 68154
  • New York
    • Albany, New York, United States, 12208
    • New Hyde Park, New York, United States, 11040
  • Ohio
    • Columbus, Ohio, United States, 43205
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • South Carolina
    • Charleston, South Carolina, United States, 29425
    • Charleston, South Carolina, United States, 29203
  • Texas
    • San Antonio, Texas, United States, 78212
  • Utah
    • Salt Lake City, Utah, United States, 84132

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• > 16 years of age
• Confirmed Diagnosis of Cystic Fibrosis
• Positive sputum culture for P. aeruginosa within the past 6 months
• Patients are able to elicit an FEV1 >/= 40% of predicted value at screening
• Clinically stable with no evidence of acute respiratory or lower respiratory infections within 28 days prior to dosing
• Able to reproducibly perform spirometry measurements and be able to repeatedly produce sputum over several hours

Exclusion Criteria:

• Use of any nebulized or systemic antibiotics within 4 weeks of starting study
• History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
• Uncontrolled diabetes or abnormal renal function
• Tobacco use (smoking) in the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: placebo; BID
Experimental: 1; Inhaled Levofloxacin	Drug: MP-376 (Levofloxacin solution for Inhalation); 40, 80, 120mg RDD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of MP-376 administered twice a day for 14 days	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate changes in the microbiology of CF sputum after 14 days of treatment with MP-376	14 days
PK Profile of single-dose vs multi-dose of MP-376	14 days
Evaluate changes in FEV1 and FVC over 14 days of Treatment	14 days

Collaborators and Investigators

• Sponsor: Horizon Pharma USA, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: July 16, 2007
• First Submitted That Met QC Criteria: July 16, 2007
• First Posted (Estimate): July 18, 2007

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: January 17, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin
• Other Study ID Numbers: Mpex-203