Trial of Aeroquin Versus Tobramycin Inhalation Solution (TIS) in Cystic Fibrosis (CF) Patients - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: MP-376 (Levofloxacin Solution for Inhalation) Drug: TIS (Tobramycin Inhalation Solution)	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 3, Open-label, Randomized Trial to Evaluate the Safety and Efficacy of MP-376 Inhalation Solution (Aeroquin) vs. Tobramycin Inhalation Solution (TIS) in Stable CF Patients

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Tobramycin Tobramycin sulfate Ofloxacin Levofloxacin Ofloxacin hydrochloride

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by Forest Laboratories:

Primary Outcome Measures:

Safety [ Time Frame: 168 and 336 days ]
Assessment of adverse events and safety from Baseline through Final Visit

Extension portion of Study: Descriptive statistics for all patients receiving at least one dose of MP-376 in the extension phase of the study will be summarized for the safety, microbiology, and disease-related endpoints. No formal hypothesis tests are planned.
Efficacy [ Time Frame: 28 Days ]
Percent change in percent predicted FEV1 from Baseline to Day 28

Secondary Outcome Measures:

Changes in respiratory and other domains of CFQ-R from Baseline to Day 28 [ Time Frame: 28 days ]
Evaluate changes in FEV1 and FVC from Baseline to Day 28 [ Time Frame: 28 days ]
Changes in bacterial load and susceptability patterns of isolated organisms from Baseline to Day 28 [ Time Frame: 28 days ]


Enrollment:	267
Study Start Date:	January 2011
Study Completion Date:	June 2013
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Aeroquin Aeroquin, Inhaled Levofloxacin (MP-376)	Drug: MP-376 (Levofloxacin Solution for Inhalation) MP-376 (Aeroquin, Levofloxacin solution for Inhalation) 240 mg administered BID for 28-days treatment followed by 28 days off treatment Other Name: (Aeroquin, Levofloxacin solution for Inhalation)
Active Comparator: TIS Tobramycin Inhalation solution (TIS) [TOBI® Novartis Pharmaceuticals]	Drug: TIS (Tobramycin Inhalation Solution) Tobramycin Inhalation Solution administered BID over 3 consecutive cycles of 28-days treatment followed by 28 days off treatment Other Name: TOBI

Detailed Description:

This study will assess the comparative safety of MP-376 (Aeroquin) and Tobramycin Inhalation solution (TIS) [TOBI® Novartis Pharmaceuticals] over three consecutive cycles of 28-days treatment followed by 28-days off in stable CF patients with chronic P. aeruginosa lung infection. Efficacy data for MP-376 and TIS at the end of the first 28-day treatment period will also be compared, as well as explored over multiple treatment cycles.

Study patients participating in Mpex 209 will be given the option to participate in a six-month open label extension phase of the Mpex 209 protocol. The open label extension will allow enrolled patients to receive three additional courses of MP-376 (levofloxacin inhalation solution, Aeroquin™).

Eligibility


Ages Eligible for Study:	12 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria (selected):

> 12 years of age
Confirmed Diagnosis of Cystic Fibrosis
Positive sputum culture for P. aeruginosa 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 tobramycin 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 inhaled or systemic aminoglycosides including tobramycin or any excipients
Evidence of acute upper within 10 days or lower respiratory infections within 28 days prior to dosing
CrCl < 20 at Screening
History of lung transplantation

Extension Portion of the Study: Patients enrolled in Mpex 209 are permitted to participate in the open label extension as long as they complete Visit 7 (Day 168), provide informed consent for participation in the open label extension of in the study and are clinically stable, as assessed by the Investigator.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01270347

Show 130 Study Locations

Sponsors and Collaborators

Forest Laboratories

Investigators


Principal Investigator:	Patrick Flume, M.D.	Medical University of South Carolina

More Information


Responsible Party:	Forest Laboratories
ClinicalTrials.gov Identifier:	NCT01270347 History of Changes
Other Study ID Numbers:	Mpex-209
Study First Received:	January 3, 2011
Last Updated:	July 11, 2013

Additional relevant MeSH terms:


Fibrosis Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pharmaceutical Solutions Levofloxacin Ofloxacin	Tobramycin Anti-Infective Agents, Urinary Anti-Infective Agents Renal Agents Anti-Bacterial Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 14, 2017

Trial of Aeroquin Versus Tobramycin Inhalation Solution (TIS) in Cystic Fibrosis (CF) Patients (TIS)