A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension (ORBIT-4) - Pulmaquin® with Non-Cystic Fibrosis Bronchiectasis (ORBIT 3)

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2013-005366-19-HU
• Date of registration: 21/03/2014
• Prospective Registration: Yes
• Primary sponsor: Aradigm Corporation
• Public title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension (ORBIT-4) - Pulmaquin® with Non-Cystic Fibrosis Bronchiectasis (ORBIT 3)
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension (ORBIT-4) - Pulmaquin® with Non-Cystic Fibrosis Bronchiectasis (ORBIT 3)
• Date of first enrolment: 08/05/2014
• Target sample size: 255
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005366-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, France, Georgia, Germany, Hungary, Israel, Italy, New Zealand, Poland, Romania, Serbia, Spain, United Kingdom, United States

Contacts

• Name: Chief Medical Officer
• Affiliation: Aradigm Corporation

• Name: Chief Medical Officer
• Affiliation: Aradigm Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
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 (or high resolution 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 forced expiratory volume in 1 second (FEV1) = 25% of predicted values at the Screening Visit (Visit 0).
6. 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). Subjects without documented P. aeruginosa prior to Screening who meet all other eligibility criteria must have at least two sputum samples or deep-throat swabs collected 3-4 or more weeks apart from each other during the 42-day Screening Phase. Two of the samples collected must test positive for P. aeruginosa. These two positive tests must be from samples taken a minimum of 3-4 or more weeks apart.
7. Have positive P. aeruginosa in the sputum/deep-throat swab culture collected at the Screening Visit (Visit 0) and at least one P. aeruginosa isolate non-resistant to ciprofloxacin. If the sputum sample is negative for P. aeruginosa, or only shows resistant P. aeruginosa isolates, the sputum/swab culture can be repeated multiple times during Screening to document the presence of P. aeruginosa. In subjects without documented P. aeruginosa prior to Screening who meet all other eligibility criteria and who had two or more sputum cultures or deep-throat swab cultures obtained 3-4 or more weeks apart from each other during Screening, at least one P. aeruginosa isolate taken after 3-4 or more weeks must be non-resistant to ciprofloxacin for the subject to be considered eligible for randomization. The qualifying sputum culture results must be available within the 42-day Screening Phase.
8. Are clinically stable and capable of performing the 6mwt without supplemental oxygen.
9. Are willing and able to comply with the requirements for participation in the study.
10. 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 or injectable hormonal contraceptives, surgical intervention, and intrauterine device (IUD).
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 stud
Exclusion criteria:
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 signing the ICF and randomization), defined as requiring acute treatment with inhaled, oral, or intravenous antibiotics.
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, clarithromycin 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 PK 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 (prednisone or prednisolone equivalents) 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, clarithromycin or erythromycin
b. Inhaled hypertonic saline or inhaled mannitol
c. Mucolytics
d. Bronchodilator medications
e. Oral corticosteroid
12. Have had changes in pulmonary rehabilitation, chest 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 and are currently receiving antibiotic treatment or are anticipated to require initiation of antibiotic treatment during the study.
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 42 days prior to Visit 1.
21. Have a malignancy or any other serious or active medical illness with a life expectancy of less than 12 months.
22. 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.
23. Have a history or suspicion of unreliability, poor cooperation, or non-compliance with medical treatment.
24. Are unable to use nebulizers during the course of the study.
25. Are unable either to understand the instruction for use of the study drug or to complete the Quality of Life Questionnaire-Bronchiectasis (QoL-B) at Visit 1.
26. Have previously been randomized in this study.
27. 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.
28. Have any other condition that, in the opinion of the Investigator, would prohibit the subject from

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

Health Condition(s) or Problem(s) studied

Chronic lung infections with Pseudomonas aeruginosa in subjects with non-cystic fibrosis bronchiectasis.
MedDRA version: 18.0 Level: PT Classification code 10057582 Term: Lung infection pseudomonal System Organ Class: 10021881 - Infections and infestations
MedDRA version: 18.0 Level: LLT Classification code 10006446 Term: Bronchiectasis NOS System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Pulmaquin®
Product Code: ARD-3150
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Ciprofloxacin Hydrochloride
CAS Number: 86483-48-9
Current Sponsor code: Ciprofloxacin for Inhalation (CFI)
Other descriptive name: CIPROFLOXACIN HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Ciprofloxacin Hydrochloride
CAS Number: 86483-48-9
Current Sponsor code: Free Ciprofloxacin for Inhalation (FCI)
Other descriptive name: CIPROFLOXACIN HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline (Day 1) to Week 48.

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 in subjects with non-Cystic Fibrosis (non-CF) bronchiectasis by evaluating the time to first pulmonary exacerbation 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.

Secondary Objective: The secondary objectives of this study are to evaluate the following:
• 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.
• Microbiological response in the Double-Blind Phase and the Open-Label Extension.
• Safety and tolerability of Pulmaquin compared to placebo in the Double-Blind Phase.
• Safety and tolerability of Pulmaquin in the Open-Label Extension.

Secondary Outcome(s)

Secondary end point(s): • Number of pulmonary exacerbations from baseline (Day 1) to Week 48.
• Number of severe pulmonary exacerbations from baseline (Day 1) to Week 48.
• Change in Respiratory Symptoms Domain score of QoL-B from baseline (Day 1) to Week 48.

Timepoint(s) of evaluation of this end point: From baseline (Day 1) to Week 48.

Secondary ID(s)

2013-005366-19-GB

NCT02104245

ARD-3150-1202

Source(s) of Monetary Support

Aradigm Corporation

Ethics review

Status: Approved
Approval date: 29/04/2014
Contact:

Results

• Results available: Yes
• Date Posted: 25/04/2018
• Date Completed: 12/10/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005366-19/results