E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute exacerbation of non-cystic fibrosis bronchiectasis due to Pseudomonas aeruginosa infection. |
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E.1.1.1 | Medical condition in easily understood language |
Worsening bronchiectasis caused by Pseudomonas aeruginosa bacterium |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy of POL7080 administered for 10 to 14 days in the treatment of patients with acute exacerbation of non-cystic fibrosis bronchiectasis due to Pseudomonas aeruginosa infection. |
|
E.2.2 | Secondary objectives of the trial |
?To investigate POL7080 for the following parameters:
a.Safety and tolerability.
b.Pharmacokinetics/pharmacodynamics of POL7080. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male* and female** aged ?18 to <80 and suffering from documented non-cystic fibrosis bronchiectasis***.
* Men should practice contraception up to 75 days after the end of treatment.
**Women of child bearing potential should practice a reliable method of contraception up to 30 days after the end of treatment.
***The diagnosis of bronchiectasis must have been made by high-resolution computed tomography or by bronchogram and documented in the patient?s record.
2. Patients currently having an exacerbation with:
Increased cough.
Increased volume of sputum production.
Increase in sputum purulence.
3. Patients with documented Pseudomonas aeruginosa infection for the current episode or a positive rapid test for Pseudomonas aeruginosa in the sputum at inclusion or known to be chronically infected with Pseudomonas aeruginosa in the past or isolation of Pseudomonas aeruginosa in the sputum culture at least 2 times in the last 12 months prior to inclusion (from patient records).
4. Sputum sample collected for quantitative culture before starting treatment.
5. Venous access available for IV dosing.
6. Written informed consent from patient. |
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E.4 | Principal exclusion criteria |
1. Female patients who are pregnant or breast feeding or unwilling to follow reliable method of contraception (in women of child bearing age). Men who are unwilling to follow contraception.
2. Subjects suffering from cystic fibrosis, active pulmonary mycobacterial infection, end stage chronic obstructive pulmonary disease on long term oxygen therapy, severe uncontrolled asthma, active sarcoidosis and active allergic broncho-pulmonary aspergillosis.
3. Current exacerbation of bronchiectasis is associated with lung abscess or empyema.
4. Current exacerbation episode is suspected or documented to be due to pathogens other than Pseudomonas aeruginosa.
5. Change or addition to maintenance anti-pseudomonas antibiotics including inhalation antibiotics within 4 weeks prior to current exacerbation.
6. Change or increase in total daily dose of maintenance macrolide antibiotics within 8 weeks prior to current exacerbation.
7. Change or increase in total daily dose of systemic or local corticosteroids or NSAIDs within 8 weeks prior to current exacerbation.
8. Patients with known HIV infection with CD4+ cell count < 200/mm3.
9. Patients with life threatening arrhythmia identified at study baseline or having been diagnosed and/or treated for life threatening arrhythmia in the last 6 months.
10. Concomitant morbidity of such severity that the patient is likely to die or present with serious medical conditions within 6 weeks of study entry.
11. Patients who are currently enrolled in, or have not yet completed at least 30 days since ending another investigational device or drug trial or are receiving other investigational agent.
12. Creatinine clearance <60mL/min. If the patient develops renal insufficiency (with creatinine clearance of <50mL/minute in 2 consecutive measurements within 24 hours) after the inclusion, the POL7080 treatment should be discontinued and the patient treated with different anti pseudomonas antibiotic(s) as per the discretion of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sputum Bacterial clearance [reduction in the daily quantitative viable counts of (cfu/mL) Pseudomonas aeruginosa by at least 1-log]. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint will be evaluated througout the study |
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E.5.2 | Secondary end point(s) |
1. Safety and tolerability of POL7080 by evaluating adverse events (AEs), changes in vital signs, physical examination results, blood chemistry, haematology and ECG parameters.
2. Pharmacokinetics/pharmacodynamics of POL7080, by assessing the correlation of selected PK parameters of POL7080 with primary end points and selected secondary end points.
3. Time to log reductions in cfu/mL of Pseudomonas aeruginosa as compared to baseline.
4. 24-h sputum volume.
5. Sputum purulence score.
6. Total WBC count, serum C-reactive protein (CRP) and procalcitonin (PCT).
7. Lung function tests: FEV1 (% predicted), FVC (% predicted), FEV1/FVC ratio.
8. Microbiology:
a) The in vitro susceptibility [(MIC - minimum inhibitory concentration performed at the central laboratory) of POL7080 and selected anti pseudomonas antimicrobials for the baseline Pseudomonas aeruginosa isolates will be summarised and compared.
b) All Pseudomonas aeruginosa isolates that show any increase in MIC to POL7080, as compared to baseline, during the daily sputum culture will be summarized. The sero typing results of such isolates will also be presented.
c) Microbiological response at TOC.
9. Patient Reported Outcome (PRO): Leicester Cough Questionnaire (LCQ), St. George`s Respiratory Questionnaire (SGRQ).
10. Evaluation of following biomarkers: Sputum Myeloperxidase (SMPO), Sputum Elastase Activity (SEA), sputum cell counts, IL6 and IL8 (wherever possible). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoint will be evaluated througout the study |
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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 | No |
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 | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
End of study: Test of cure (TOC) assessment for the last patient.
Test-of-Cure (TOC) is the time of the primary end point assessment at 4± 1 day after EOT. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |