Clinical trial NCT00503490: Safety, Pharmacokinetic and Pharmacodynamic Study of MP-376 in Patients With Cystic Fibrosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2007-07-18
Enrollment: 40
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. 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.

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 acquired from Horizon in 2024.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of MP-376 administered twice a day for 14 days
timeFrame: 14 days
Secondary outcomes:
measure: Evaluate changes in the microbiology of CF sputum after 14 days of treatment with MP-376
timeFrame: 14 days
measure: PK Profile of single-dose vs multi-dose of MP-376
timeFrame: 14 days
measure: Evaluate changes in FEV1 and FVC over 14 days of Treatment
timeFrame: 14 days
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Kalamazoo
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Albany
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Charleston
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: