Trial registered on ANZCTR


Trial ID
ACTRN12609000578202
Ethics application status
Approved
Date submitted
10/07/2009
Date registered
14/07/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
An International, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Mixture Formulation Consisting of Liposomal and Free Ciprofloxacin for Inhalation Compared with Placebo for Inhalation in the Management of Pseudomonas aeruginosa in Patients with Non-Cystic Fibrosis Bronchiectasis with Chronic Lung Infections.
Scientific title
An International, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Mixture Formulation Consisting of Liposomal and Free Ciprofloxacin for Inhalation Compared with Placebo for Inhalation in the Management of Pseudomonas aeruginosa in Patients with Non-Cystic Fibrosis Bronchiectasis with Chronic Lung Infections
Universal Trial Number (UTN)
Trial acronym

Health condition
Health condition(s) or problem(s) studied:
Non cystic fibrosis (CF) bronchiectasis 237190 0
Condition category
Condition code
Respiratory 237513 237513 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 2a, international, multicenter, randomized, double-blind, placebo controlled study designed to evaluate safety and efficacy of the mixture formulation consisting of liposomal and free ciprofloxacin for inhalation compared to placebo for inhalation in patients with non CF bronchiectasis with chronic lung infection. Patients will be enrolled in this study for 6 months. This study will consist of a 14 day Screening Phase and a Treatment Phase consisting of three 28 day On treatment Periods (Months 1, 3, and 5) and three 28 day Off treatment Periods (Months 2, 4, and 6). Patients will have a one week wash out period after each treatment period.

Patients will be randomised to receive one of the following inhaled treatment regimens, which will be administered via nebulizer once daily during the three 28 day On-treatment Periods (Months 1, 3, and 5):
Mixture Formulation, which consists of the following:
Liposomal Ciprofloxacin and
Free Ciprofloxacin Or Placebo.
Intervention code [1] 236896 0
Treatment: drugs
Comparator / control treatment
Mixture Formulation, which consists of the following:
Liposomal Ciprofloxacin and Free Ciprofloxacin
Control group
Placebo

Outcomes
Primary outcome [1] 238342 0
The primary objective of this study will be to determine whether the microbiological efficacy of the mixture formulation consisting of Ciprofloxacin for Inhalation (CFI) and Free ciprofloxacin for Inhalation (FCI) is superior to placebo for inhalation in the treatment of patients with non Cystic fibrosis (CF) bronchiectasis by evaluating changes in Pseudomonas aeruginosa log10 Colony Forming Units (CFU)/gram of sputum from Baseline to Day 28.
Timepoint [1] 238342 0
The primary endpoint of this study will evaluate microbiological efficacy from Baseline to Day 28 on the following: Mean change in Pseudomonas aeruginosa density in sputum (log10) Colony Forming Units (CFU)/gram of sputum from Baseline to Day 28.
Secondary outcome [1] 244750 0
The secondary microbiological efficacy endpoints to be evaluated are the following: Mean change in Pseudomonas aeruginosa density in sputum (log10) CFU/gram of sputum from Baseline to Days 14, 56, 84, 112, 140, and 168
Timepoint [1] 244750 0
Mean change in Pseudomonas aeruginosa density in sputum (log10) CFU/gram of sputum from Baseline to Days 14, 56, 84, 112, 140, and 168.
Secondary outcome [2] 244795 0
Incidence of isolation of other sputum pathogens from Day 1 to Days 14, 28, 56, 84, 112, 140, and 168.
Timepoint [2] 244795 0
Incidence of isolation of other sputum pathogens from Day 1 to Days 14, 28, 56, 84, 112, 140, and 168.
Secondary outcome [3] 244796 0
Change in ciprofloxacin minimum inhibitory concentration (MIC) for P. aeruginosa from Day 1 to Days 14, 28, 56, 84, 112, 140, and 168.
Timepoint [3] 244796 0
Change in ciprofloxacin minimum inhibitory concentration (MIC) for P. aeruginosa from Day 1 to Days 14, 28, 56, 84, 112, 140, and 168.
Secondary outcome [4] 244797 0
Clinical Exacerbation Endpoints
Timepoint [4] 244797 0
Clinical exacerbation endpoints will evaluate exacerbations that occur from Day 1 to Day 168.
Secondary outcome [5] 244798 0
Spirometry Endpoints
Timepoint [5] 244798 0
Spirometry efficacy endpoints to be evaluated from Day 1 to Days 14, 28, 56, 84, 112, 140, and 168.
Secondary outcome [6] 244799 0
Quality of Life
Timepoint [6] 244799 0
Quality of life will be evaluated from Day 1 to Days 14, 28, 56, 84, 112, 140, and 168.
Secondary outcome [7] 244800 0
Safety and Tolerability
Timepoint [7] 244800 0
Safety and tolerability will be assessed from day 1 to the end of study.

Eligibility
Key inclusion criteria
1. Are willing and able to provide written informed consent.
2. Are males or females 18 to 80 year of age, inclusive, who are able to walk.
3. Have had a confirmed diagnosis of non-CF bronchiectasis per high resolution computed tomography.
4. Have a confirmed history of at least two exacerbations treated with a course of antibiotics within the last 12 months.
5. Have been off any anti-pseudomonal antibiotic for a minimum of 28 days prior to the Screening Visit (Visit 0).
6. Have FEV1 of more than 25% of predicted values at the Screening Visit (Visit 0).
7. Have positive documented Pseudomonas aeruginosa in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to the Screening Visit (Visit 0) and in the sputum/ deep-throat cough swab culture collected at the Screening Visit (Visit 0).
8. Are clinically stable in the opinion of the investigator.
9. Are willing to comply with the requirements for participation in the study.
10. Are willing to use an acceptable method of contraception during the study.
11. Female patients of childbearing potential must provide a negative pregnancy test at the Screening Visit and must use an acceptable method of contraception for at least 3 weeks prior to the first dose of study drugs and for 30 days after the last dose of study drugs. Acceptable methods of contraception for women are orally administered hormonal contraceptives, surgical intervention, intrauterine device (IUD), and sexual abstinence. If a hormonal contraceptive is utilized as the method of contraception, the same method must have been used for at least 3 months prior to Visit 1.
To be considered “not of child bearing potential”, female patients must be at least 2 years postmenopausal, 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 drugs.
Male patients whose female partners are of child bearing potential (definition as above) must agree to use an acceptable method of birth control (as listed above) for the duration of study treatment and for 30 days after the last dose of study drugs.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have a known local or systemic hypersensitivity to fluoroquinolone or quinolone antibiotics.
2. Have an exacerbation during the Screening Phase as defined as requiring treatment with inhaled, oral, or intravenous antibiotics prior to the first dose of study drugs.
3. Have a diagnosis of cystic fibrosis.
4. Have a diagnosis of allergic brochopulmonary aspergillosis.
5. Have received any intravenous, oral, or inhaled anti-pseudomonal antibiotic within 28 days prior to Visit 1.
6. Have used tizanidine within 28 days prior to Visit 1.
7. Have used supplemental oxygen within 28 days prior to Visit 1.
8. 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.
9. 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:
Azithromycin
Hypertonic saline
Mucolytics
Bronchodilator medications
Oral corticosteroid
10. Have had changes in physiotherapy technique or schedule within 28 days prior to Visit 1.
11. Have a history of solid organ (e.g., lung) transplantation.
12. Have a history of non-tuberculosis mycobacteria requiring treatment within 12 months prior to Visit 1.
13. Have serum creatinine levels greater than 1.5x upper limit of normal (ULN) at the Screening Visit (Visit 0).
14. Have serum transaminase levels >3x ULN at the Screening Visit (Visit 0).
15. Have a febrile illness within 1 week prior to Visit 1.
16. Have had massive hemoptysis (greater than or equal to 300 mL or requiring blood transfusion) within 6 months prior to Visit 1.
17. Have used any over-the-counter product, herbal product, diet aid, hormone supplement, etc., within 7 days prior to dosing unless approved by both the Principal Investigator and the Sponsor.
18. Have received an investigational drug or device within 28 days prior to Visit 1.
19. Have any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patients’ treatment, assessment, or compliance with the protocol.
20. Have a history or suspicion of unreliability, poor cooperation, or non-compliance with medical treatment.
21. Are unable to use nebulizers.
22. Are unable either to understand the instruction for use of the study drugs or to complete the Quality of life (QoL) questionnaire at Visit 1.
23. Have previously been enrolled in this study.
24. 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.
Patients who meet all inclusion and none of the exclusion criteria and meet the following sputum criteria at screening will be enrolled into the study:
Sputum positive for Pseudomonas aeruginosa
Sputum Pseudomonas aeruginosa sensitive to ciprofloxacin

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After signing the consent form, each patient will be assigned a screening number. This will be done via an e-mail based computer system that will generate randomization sequence numbers for each screened patient. Patients who drop out of the study before randomization will retain their screening number. Randomization will occur at Visit 1 after all screening procedures have been performed and eligibility for the study is confirmed. Patients will be randomized to either receive the mixture formulation or placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
After signing the consent form, each patient will be assigned a screening number. Randomisation numbers are generated by a computer software system.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy

Recruitment
Anticipated date of first participant enrolment
1/10/2009
Actual date of first participant enrolment
Anticipated date last participant enrolled
Actual date last participant enrolled
Target sample size
40
Actual sample size
Recruitment status
Recruiting
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 1875 0
New Zealand
State/province [1] 1875 0
Auckland, Tauranga, Wellington, Christchurch

Funding & Sponsors
Funding source category [1] 237307 0
Commercial sector/Industry
Name [1] 237307 0
Aradigm Corporation
Address [1] 237307 0
3929 Point Eden Way Hayward, CA 94545
Country [1] 237307 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Aradigm Corporation
Address
3929 Point Eden Way Hayward, CA 94545
Country
United States of America
Secondary sponsor category [1] 236792 0
Commercial sector/Industry
Name [1] 236792 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 236792 0
Level 3, 88 Jephson Street Toowong, Brisbane, QLD 4066
Country [1] 236792 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239402 0
Mater Adult Hospital
Ethics committee address [1] 239402 0
Department of Respiratory Medicine, Level 9, Raymond Terrace, South Brisbane, Queensland, 4101.
Ethics committee country [1] 239402 0
Australia
Date submitted for ethics approval [1] 239402 0
10/07/2009
Approval date [1] 239402 0
Ethics approval number [1] 239402 0

Summary
Brief summary
This study will compare the safety and efficacy of the mixture formulation consisting of liposomal and free ciprofloxacin for inhalation to placebo for inhalation in patients who have a confirmed diagnosis of non-CF bronchiectasis with a history of chronic Pseudomonas Aeruginosa infections.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29867 0
Address 29867 0
Country 29867 0
Phone 29867 0
Fax 29867 0
Email 29867 0
Contact person for public queries
Name 13114 0
CNS Project Manager
Address 13114 0
Clinical Network Services (CNS) Pty Ltd Level 4, 88 Jephson Street, Toowong, Brisbane, QLD, 4066
Country 13114 0
Australia
Phone 13114 0
+61 7 3719 6000
Fax 13114 0
+61 7 3719 6011
Email 13114 0
cns@clinical.net.au
Contact person for scientific queries
Name 4042 0
CNS Project Manager
Address 4042 0
Clinical Network Services (CNS) Pty Ltd Level 4, 88 Jephson Street, Toowong, Brisbane, QLD, 4066
Country 4042 0
Australia
Phone 4042 0
+61 7 3719 6000
Fax 4042 0
+61 7 3719 6011
Email 4042 0
cns@clinical.net.au