E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pseudomonas aeruginosa infection in patients suffering from stable Cystic Fibrosis |
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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 | 10011763 |
E.1.2 | Term | Cystic fibrosis lung |
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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 | 10021860 |
E.1.2 | Term | Infection pseudomonas aeruginosa |
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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 efficacy of three dosage regimens of MP-376 administered over 28 days, compared to placebo
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of three dosage regimens of MP-376 administered over 28 days, compared to placebo
To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) relationships for levofloxacin with MP-376 administration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Are at least 16 years of age (at least 18 years of age in Germany and the Netherlands). 2. Have a clinical diagnosis of CF based on the following criteria: a) positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or b) a genotype with two identifiable mutations consistent with CF, and c) accompanied by one or more clinical features consistent with the CF phenotype. 3. Are able to elicit an FEV1 > 25% but < 85% predicted value at screening based on Hankinson/NHanes criteria (reference Hankinson, et. al). 4. Have received at least 3 courses of inhaled antimicrobials over the preceding 12 months and have received at least one course of inhaled tobramycin/TOBI®/colistin in the 2 months prior to Visit 1, but none in the 28 days prior to Visit 1. 5. Must have a sputum specimen at screening positive for P. aeruginosa and have a history of at least one positive sputum culture positive for P. aeruginosa within the last 18 months. 6. Clinically stable with no significant changes in health status within the last 30 days. 7. Are able to perform spirometry reproducibly. 8. Have not smoked tobacco within 30 days prior to Visit 1 and agree not to smoke for the duration of the study. 9. Are able to reproducibly expectorate sputum. 10. Are able to and have given written informed assent/consent in a manner approved by the Institutional Review Board/Ethics Committee and are willing to comply with the requirements of the study. |
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E.4 | Principal exclusion criteria |
1. Have used an investigational agent within 30 days prior to Visit 1. 2. Have used any nebulized or systemic antibiotics active against P. aeruginosa within 30 days prior to Visit 1, other than maintenance oral azithromycin, which must be have been initiated at least 30 days prior to Visit 1. 3. History of hypersensitivity to fluoroquinolones or excipients of MP-376 (magnesium chloride). 4. History of intolerance to bronchodilators or unwilling to use a bronchodilator during the study. 5. Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day. 6. Changes in physiotherapy technique or schedule within 14 days prior to Visit 1. 7. Changes in medical regimen for treatment of CF (e.g., introduction, dose escalation, or elimination of therapies such as dornase alfa, non-steroidal anti-inflammatory agents, azithromycin, hypertonic saline, or inhaled corticosteroids) within 30 days of Visit 1. 8. History of lung transplantation 9. Evidence of acute upper respiratory tract infection within 10 days or lower respiratory tract infection within 30 days prior to Visit 1 10. Are pregnant, breastfeeding, or unwilling to practice birth control or abstinence during participation in the study (women only). 11. Have a history of seizures or low seizure threshold (e.g., epilepsy). 12. Have renal dysfunction (calculated CrCl < 50ml/min) at Screening. 13. Have AST, ALT or total bilirubin ≥ 3 x upper limit of normal (ULN) at screening or evidence of severe liver disease (e.g., cirrhosis, portal hypertension). 14. Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection/seropositivity. (Based on medical history, screening labs are not required.) 15. Have a history of hemoptysis ≥ 30 mLs over any 24 hour period during the 30 days prior to Visit 1. 16. Have an oxygen saturation < 90% on room air at Screening or Visit 1. 17. Have a > 15% relative decline in FEV1 (L) from Screening to Visit 1. 18. Are a dependent (as an employee or relative) of the sponsor, contract research organization or Investigator. 19. Have a present condition, or abnormality in screening laboratory tests or physical examination findings, that in the opinion of the Investigator or Medical Monitor would compromise the safety of the patient or the quality of the data. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint Change in P. aeruginosa density (log10 colony-forming units [CFU] per gram sputum) from Visit 1 to Visit 4
Secondary Endpoints
Clinical • Changes in respiratory and other domains of CFQ-R from Visit 1 to Visit 4 •Time to administration of IV/oral/inhaled anti-pseudomonal antimicrobials in patients with at least one of the following: - Decreased exercise tolerance - Increased cough - Increased sputum/chest congestion - Decreased appetite
Microbiology • Change in P. aeruginosa density (log10 colony-forming units [CFU] per gram sputum) from Visit 1 to all subsequent scheduled study visits at which sputum for microbiology is collected (Study Visits 2, 3, 4, and Final/Early Term). • Changes in bacterial load of all organisms from Visit 1 to all subsequent scheduled study visits at which sputum for microbiology is collected (Study Visits 2, 3, 4 and Final Visit) • Changes in susceptibility patterns of isolated organisms from Visit 1 to all subsequent scheduled study visits at which sputum microbiology is collected (Study Visits 2, 3, 4 and Final Visit)
Pulmonary Function • Mean percent change in FEV1, FVC, and FEF 25-75 from Visit 1 to all subsequent scheduled study visits at which PFTs are collected (Study Visits 3, 4 and Final Visit).
Pharmacokinetic Evaluation • Population and Bayesian estimates of levofloxacin (e.g. AUC, Cmax, Cmin)
Safety • Assessment of adverse events and drug intolerability from Visit 1 through end of study between treatment groups will be evaluated. • Changes from Visit 1 in physical examination findings, pulse oximetry results, pulmonary function tests, safety laboratory test results and vital signs will be evaluated. |
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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 | No |
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 | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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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The end of the study is defined as the last visit of the last patient. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |