Trial of Aeroquin versus Tobramycin Inhalation Solution (TIS) in Stable Cystic Fibrosis Patients

• Register: EUCTR
• Last refreshed on: 17 February 2014
• Main ID: EUCTR2010-019634-26-IE
• Date of registration: 15/02/2011
• Prospective Registration: Yes
• Primary sponsor: Mpex Pharmaceuticals, Inc.
• Public title: Trial of Aeroquin versus Tobramycin Inhalation Solution (TIS) in Stable Cystic Fibrosis Patients
• Scientific title: A Phase 3, Open-Label, Randomized Trial to Evaluate the Safety and Efficacy of MP-376 Inhalation Solution (Aeroquin™) versus Tobramycin Inhalation Solution (TIS) in Stable Cystic Fibrosis Patients
• Date of first enrolment: 03/05/2011
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019634-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Canada, France, Germany, Ireland, Israel, United Kingdom, United States

Contacts

• Name: Elizabeth E Morgan
• Affiliation: Mpex Pharmaceuticals, Inc

• Name: Elizabeth E Morgan
• Affiliation: Mpex Pharmaceuticals, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Patients will be included in the study if they meet all of the following criteria:
1. Are at least 12 years of age
2. Weigh at least 30 kilograms (kg) or 66 pounds
3. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
a) sweat chloride > 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)
b) two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
c) abnormal nasal potential difference
4. Are able to elicit an FEV1 > 25% but < 85% predicted value at screening based on
Hankinson/NHanes III criteria
5. Must have a sputum or throat swab (if unable to produce sputum) specimen at screening positive for P. aeruginosa and have a history of at least one additional sputum culture positive for P. aeruginosa within the last 12 months prior to Visit 1
6. Must have received at least three 28 day courses or a total of 84 days of an inhaled tobramycin over the previous 12 months, with at least a minimum 14 day course being finished within 29-56 days prior to Visit 1
7. Clinically stable with no significant changes in health status within the last 28 days prior to Visit 1
8. Are able to perform an acceptable spirometry session (defined as 3 acceptable or usable efforts per ATS/ERS criteria at Screening
9. Have not smoked tobacco within 28 days prior to Visit 1 and agree not to smoke for the duration of the study
10. Are able to and have given written informed consent (if they are adults) or assent in combination with consent of their legal representative(s) (if they are minors) in a manner approved by the Institutional Review Board/Ethics Committee, and are willing to comply with the requirements of the study
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 214
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Patients will be excluded from the study if they meet any of the following criteria:
1. Have used an investigational agent within 28 days prior to Visit 1
2. Have used any nebulized or systemic antimicrobials active against P. aeruginosa within 28 days prior to Visit 1, other than maintenance oral azithromycin, which must have been initiated at least 28 days prior to Visit 1
3. History of hypersensitivity or intolerance to fluoroquinolones (e.g. joint or tendon disorders), or any excipients of MP-376 (magnesium chloride)
4. History of hypersensitivity or intolerance to inhaled or systemic aminoglycosides, including tobramycin or any excipients of TIS (sodium chloride, sulfuric acid, sodium hydroxide)
5. History of intolerance to bronchodilators or unwilling to use a bronchodilator during the study
6. Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day at Screening or Visit 1
7. Changes in technique or schedule of physiotherapy and/or airway clearance techniques (ACT) within 14 days to Visit 1
8. Changes in medical regimen for treatment of CF (e.g., introduction, dose escalation, or elimination of therapies such as dornase alfa, non-steroidal anti-inflammatory agents, azithromycin, hypertonic saline, or inhaled corticosteroids) within 28 days of Visit 1
9. History of lung transplantation
10. Evidence of acute upper respiratory tract infection within 10 days or lower respiratory tract infection within 28 days prior to Visit 1
11. Active treatment for allergic bronchopulmonary aspergillosis (ABPA)
12. Active treatment for mycobacterial lung infection
13. Are pregnant, breastfeeding, or unwilling to practice a highly effective method of birth control or abstinence during participation in the study (women only).
14. Have a history of seizure disorder requiring anti-seizure medications (e.g., epilepsy)
15. Known history of chronic infection with human immunodeficiency virus (HIV), or chronic active hepatitis secondary to hepatitis B, and/or hepatitis C infection (Based
on medical history, screening labs are not required)
16. Have a history of hemoptysis > 30 mLs over any 24 hour period during the 28 days prior to Visit 1
17. Have a calculated creatinine clearance less than 20mL/min (Cockroft-Gault method) at Screening for patients that are = 18 years of age. Have a calculated creatinine clearance less than 20 mL/min/1.73m2 (Schwarz method) at Screening for patients that are <18 years of age
18. Have an oxygen saturation < 90% on room air at Screening or Visit 1
19. Have a > 15% relative change (increase or decline) in FEV1(L) from Screening to Visit 1
20. History of suspected auditory, vestibular, or neuromuscular dysfunction
21. Have a present condition, or abnormality in screening laboratory tests or physica
examination findings, that in the opinion of the Investigator or Medical Monitor would compromise the safety of the patient or the quality of the data
22. Are a dependent (as an employee or relative) of the sponsor, contract research organization, or investigator


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Pseudomonas aeruginosa infection in patients suffering from stable Cystic Fibrosis
MedDRA version: 14.1 Level: PT Classification code 10011763 Term: Cystic fibrosis lung System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 14.1 Level: LLT Classification code 10021860 Term: Infection pseudomonas aeruginosa System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: Aeroquin
Product Code: MP-376
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: levofloxacin
CAS Number: 100986-85-4
Other descriptive name: levofloxacin hemihydrate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: TOBI
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: TOBRAMYCIN
CAS Number: 32986-56-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are to:
1. To assess the efficacy of MP-376 and TIS on Pulmonary Function from Baseline (Visit 1/Day 1) to Day 28.

2. To assess the efficacy of MP-376 and TIS on Microbiology status from Baseline (Visit 1/Day 1) to Day 28.

3. To assess the efficacy of MP-376 and TIS on Patient Reported Outcome from Baseline (Visit 1/Day 1) to Day 28.

4. To assess the efficacy of MP-376 and TIS on Exploratory Efficacy Endpoints as follows:
Change in clinical status from Baseline (Visit 1/Day 1) to Day 140.
Change in Pulmonary Function status from Baseline (Visit 1/Day 1) to Day 140.
Change in Microbiology status from Baseline (Visit 1/Day 1) to Day 140.
Change in Patient Reported Outcomes from Baseline (Visit 1/Day 1) to Day 140.

5. PK Evaluations
To assess the serum and sputum concentrations of levofloxacin in patients treated with MP-376 at periodic intervals, only in patients randomized to the MP-376 group.

Primary end point(s): Primary Analysis
Assessment of adverse events and safety from Baseline (Visit 1/Day 1) through Final Visit

Primary Efficacy Endpoint:
Percent change in percent predicted FEV1 from Baseline (Visit 1/Day 1) to Day 28

Timepoint(s) of evaluation of this end point: 1. 168 days
2. 28 days

Main Objective: The primary objectives of this study are to:
1. To compare the safety of MP-376 and TIS when administered over multiple cycles
2. To compare the efficacy of MP-376 and TIS administered over 28 days

Secondary Outcome(s)

Secondary end point(s): 1. Change in respiratory and other domains of CFQ-R from Baseline to Day 28
2. Evaluate changes in FEV1 and FVC from Baseline to Day 28
3. Changes in bacterial load and susceptibility patterns of isolated organisms from Baseline to Day 28

Timepoint(s) of evaluation of this end point: 1.-3.: 28 days

Secondary ID(s)

2010-019634-26-DE

MPEX-209

Source(s) of Monetary Support

Mpex Pharmaceuticals, Inc