E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bronchiectasis Complicated by Chronic Infection due to Pseudomonas aeruginosa |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006445 |
E.1.2 | Term | Bronchiectasis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of two dose levels of nebulized Arikace™ versus placebo. |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of two dose levels of nebulized Arikace™ versus placebo. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PK Sub-Study: Pharmacokinetics (PK) of Arikace™ in urine, blood and sputum will be determined in a subgroup of study subjects who consent to PK evaluation. |
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E.3 | Principal inclusion criteria |
1) Written informed consent obtained from the patient or legal representative prior to the performance of any study related procedures 2) Male or female study subjects≥ 18 years of age 3) Confirmed diagnosis of multi-focal bronchiectasis in two or more lung segments by HRCT of the chest 4) History of chronic infection with P. aeruginosa, defined as: At least 1 documented positive culture in the 12 months prior to screening AND One or more documented courses of antibiotics for respiratory tract infection in the past 12 months, including either: One course of IV antibiotics OR One treatment failure with oral antibiotics requiring additional antibiotic treatment for respiratory tract infection 5) Confirmation of infection with P. aeruginosa at screening (defined as mucopurulent sputum positive for P. aeruginosa) 6) SaO2 ≥ 90% at Screening while breathing room air 7) Ability to comply with study medication use, study visits, and study procedures as judged by the investigator 8) Ability to produce at least 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation 9) Female of childbearing potential agrees to practice an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) |
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E.4 | Principal exclusion criteria |
1) Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted at Screening 2) Subjects with hemoptysis of ≥ 60 ml within 4 weeks prior to screening 3) Positive pregnancy test or lactation. All women of child bearing potential will be tested 4) Bronchiectasis due to cystic fibrosis (CF), bronchopulmonary Aspergillus, aspiration of foreign body, or secondary to lung compression from tumors 5) History of non-tuberculous mycobacterial and/or Aspergillus infection requiring treatment or treated within 2 years prior to screening 6) History ofAllergic Bronchopulmonary Aspergillosis requiring systemic steroid treatment or treated within 3 months prior to screening 7) Pulmonary tuberculosis requiring treatment or treated within two years prior to screening 8) History of Lung transplantation 9) More than 3 bronchiectasis exacerbations within 12 months prior to screening 10) Treatment for bronchiectasis exacerbation within the 4 weeks prior to screening. 11) Radiographic finding of new pulmonary infiltrate(s) within 2 months prior to screening 12) Presence of any clinically significant cardiac disease as determined by Investigator: The QTc criteria for Exclusion of subjects is: males QTc> 450 msec (or 0.450 seconds), females QTc> 470 msec (or 0.470 seconds) 13) Use of any inhalation or systemic antibiotics (IV antibiotics, or oral antibiotics) within 4 weeks prior to Study Day 1 14) Initiation of chronic therapy (e.g., TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics, chronic suppressive antibacterial treatment) within the 28 days prior to Study Day 1 15) Administration of any investigational drug within 8 weeks prior to screening 16) Hypersensitivity to aminoglycosides 17) Evidence of biliary cirrhosis with portal hypertension 18) AST or ALT ≥ X 3 times the upper limit of normal at Screening 19) Absolute Neutrophil Count ≤ 1000 performed at Screening 20) Serum creatinine > X1.8 times normal performed at Screening 21) History of daily, continuous oxygen supplementation 22) Smoking tobacco or any substance within 6 months prior to screening, and throughout the study 23) History of alcohol, medication, or illicit drug abuse within the 1 year prior to screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Treatment emergent adverse events up to end of treatment • Treatment emergent marked laboratory abnormalities up to 28 days after study medication discontinuation • Treatment emergent pulmonary function test (PFT) abnormalities post-dose for acute tolerability assessment • Treatment emergent pulmonary function test (PFT) abnormalities up to end of treatment • Adverse events leading to permanent discontinuation of study medication • Serious adverse events up to 28 days after study medication discontinuation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 56 |
E.8.9.2 | In all countries concerned by the trial days | 56 |