A Multi-centre, Randomised, Double-Blind, Placebo-Controlled Study to evaulate the Safety and Efficacy of Pulmaquin® (ARD-3150, Dual Release Coprofloxacin for Inhalation) in subjects who have a lung infection that includes the bacteria Pseudomonas aeruginosa due to the non-cystic fibrosis bronchiectasis
- Conditions
- Chronic lung infections with Pseudomonas aeruginosa in subjects with non-cystic fibrosis bronchiectasisMedDRA version: 16.1Level: LLTClassification code 10057582Term: Lung infection pseudomonalSystem Organ Class: 100000004862MedDRA version: 16.1Level: LLTClassification code 10006446Term: Bronchiectasis NOSSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2013-005366-19-GB
- Lead Sponsor
- Aradigm Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 255
Subjects will be entered into this study only if they meet all of the following criteria:
1. Are willing and able to provide written informed consent.
2. Are males or females who are 18 year of age or older and are able to
walk.
3. Have had a confirmed diagnosis of non-CF bronchiectasis per
computerized tomography showing bronchial wall dilatation (internal
bronchial lumen diameter greater than accompanying pulmonary artery
or lack of tapering) with or without bronchial wall thickening.
4. Have a documented history of at least 2 pulmonary exacerbations
treated with courses of antibiotics within the last 12 months.
5. Have been off any antibiotic treatment for a minimum of 28 days prior
to Visit 1, except for macrolides (azithromycin or erythromycin) used
chronically at a stable dose.
6. Have FEV1 = 25% of predicted values at the Screening Visit (Visit 0).
7. Have positive documented P. aeruginosa in a sputum/deep-throat
swab culture (or bronchoalveolar lavage [BAL] or bronchoscopic
specimen) prior to the Screening Visit (Visit 0).
8. Have positive P. aeruginosa in the sputum/deep-throat swab culture
collected at the Screening Visit (Visit 0). If sputum sample is negative,
sputum/swab culture can be repeated on up to 3 occasions during
Screening to document P. aeruginosa presence.
9. Are clinically stable and capable of performing the 6mwt without
supplemental oxygen.
10. Are willing and able to comply with the requirements for
participation in the study.
11. Female subjects of childbearing potential must have a negative
pregnancy test at the Screening Visit and must use an acceptable
method of contraception for at least 3 months prior to the first dose of
study drug and for 28 days after the last dose of study drug. Acceptable
methods of contraception for women are orally administered or
implantable hormonal contraceptives, surgical intervention, intrauterine
device (IUD), and sexual abstinence. To be considered not of
childbearing potential, female subjects must be postmenopausal for at
least 1 year as confirmed by an elevated follicle-stimulating hormone
(FSH) level (= 30 mIU/mL) at Screening and 1 year of amenorrhea, or
have been irreversibly surgically sterilized by hysterectomy,
oophorectomy, or bilateral tubal ligation for at least 3 months prior to
the first dose of study drug. Male subjects whose female partners are of
childbearing potential (definition as above) must agree to use an
acceptable method of birth control for the duration of study treatment
and for 28 days after the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55
Subjects will be randomized into this study only if they meet none of the following criteria:
1. Have a pulmonary exacerbation during the Screening Phase (between Visit 0 and randomization), defined as requiring acute treatment with inhaled, oral, or intravenous antibiotics prior to the first dose of study drug.
2. Have a clinical diagnosis of CF.
3. Have primary diagnosis of Chronic Obstructive Pulmonary Disease (COPD) related to smoking history of greater than 10 pack years.
4. Have a current diagnosis of active allergic bronchopulmonary aspergillosis.
5. Have received any intravenous, oral, or inhaled anti-pseudomonal antibiotic (except chronic macrolides erythromycin or azithromycin with a stable dose) within 28 days prior to Visit 1.
6. Have an allergy to ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, or norfloxacin.
7. Have a known allergy to soy products.
8. Have used tizanidine within 28 days prior to Visit 1 and would need to use tizanidine during the study (because tizanidine is contraindicated due to a pharmacokinetic interaction with ciprofloxacin).
9. Have initiated supplemental oxygen within 28 days prior to Visit 1.
10. Have used any intravenous or intramuscular corticosteroid or have
used oral corticosteroid > 10 mg/day or > 20 mg every other day within
28 days of Visit 1.
11. Have had changes in either the treatment regimen or initiation of
treatment with any of the following medications within 28 days prior to
Visit 1:
a. Macrolides, e.g., azithromycin or erythromycin
b. Inhaled hypertonic saline or inhaled mannitol
c. Mucolytics
d. Bronchodilator medications
e. Oral corticosteroid
12. Have had changes in physiotherapy technique or frequency within 28
days prior to Visit 1.
13. Have a history of solid organ (e.g., lung) transplantation.
14. Have a non-tuberculosis mycobacterial infection requiring treatment.
15. Have active tuberculosis.
16. Have serum creatinine levels = 2.0x upper limit of normal (ULN) at
the Screening Visit (Visit 0).
17. Have serum transaminase levels > 3x ULN at the Screening Visit
(Visit 0).
18. Have a febrile illness within 1 week prior to Visit 1.
19. Have had massive hemoptysis (greater than or equal to 300 mL or
requiring blood transfusion) within 6 months prior to Visit 1.
20. Have received an investigational drug or device within 28 days prior
to Visit 1.
21. Have any serious or active medical or psychiatric illness, which in the
opinion of the Investigator, would interfere with subjects' treatment,
assessment, or compliance with the protocol.
22. Have a history or suspicion of unreliability, poor cooperation, or noncompliance
with medical treatment.
23. Are unable to use nebulizers.
24. Are unable either to understand the instructions for use of the study
drug or to complete the QoL-B questionnaire at Visit 1.
25. Have previously been enrolled in this study.
26. Are pregnant, plan to become pregnant during this study, are nursing
mothers or are unwilling to use an acceptable method of contraception
for the duration of the study.
27. Have any other condition that, in the opinion of the Investigator,
would prohibit the subject from participating in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective of this study is to evaluate the efficacy of Pulmaquin compared to placebo in the management of chronic lung infections with P. aeruginosa (a type of bacteria) in subjects with noncystic fibrosis bronchiectasis by evaluating the time to first pulmonary exacerbation (worsening).;Secondary Objective: The secondary objectives of this study are to evaluate:<br>- Efficacy of Pulmaquin compared to placebo as assessed by clinical outcomes (including pulmonary exacerbations), pulmonary function, patient-reported outcomes, and exercise testing in the Double-Blind Phase.<br>- Microbiological response.<br>- Safety and tolerability of Pulmaquin compared to placebo in the Double-Blind Phase.;Primary end point(s): The primary efficacy endpoint of this study is the time to first pulmonary exacerbation from baseline (Day 1) to Week 48.;Timepoint(s) of evaluation of this end point: From baseline (Day 1) to Week 48.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Number of pulmonary exacerbations from baseline (Day 1) to Week 48.<br>- Number of severe pulmonary exacerbations from baseline (Day 1) to<br>Week 48.<br>- Change in Respiratory Symptoms Domain score of Qol-B from baseline<br>(Day 1) to Week 48.;Timepoint(s) of evaluation of this end point: From baseline (Day 1) to Week 48.