E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bronchiectasis
Lung infections |
Bronchiectasien
Long/luchtweg infecties |
|
E.1.1.1 | Medical condition in easily understood language |
Abnormal widening of the bronchi or their branches |
Abnormale verwijdingen van de luchtwegen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 pharmacokinetics and the local tolerabilityof dry powder tobramycin at different dosages in patients with bronchiectasis |
Het onderzoeken van de farmacokinetiek en de lokale verdraagzaamheid van droog poeder tobramycine bij patienten met bronchiectasieen |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18 years or older
• Obtained informed consent
• Patients having bronchiectasis (confirmed with HR-CT of the chest)
|
Leeftijd boven de 18 jaar
Verkregen informed consent
Voorgeschiedenis van bronchiectasieen, bewezen middels HR-CT van de thorax
|
|
E.4 | Principal exclusion criteria |
Pregnant or breast feeding
Subjects with known or suspected renal, auditory, vestibular or neuromuscular dysfunction, or with severe, active haemoptysis
History of adverse events on previous tobramycin or other aminoglycoside use
No concurrent use of ciclosporin, cisplatin, amfotericin B, cephalosporins, polymyxins, vancomycin and NSAIDs |
Zwanger of borstvoeding gevend
Personen met bekende of vermeende nier-, gehoor- of neuromuculaire dysfunctie of met ernstige, actieve hemoptysis
Voorgeschiedenis van bijwerkingen op vroeger tobramycine gebruik of een andere aminoglycoside
Niet gelijktijdig gebruik of geen mogelijkheid tot stoppen van ciclosporine, cisplatinum, amfotericin B, cephalosporinen, polymyxinen, vancomycine en NSAIDs |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The following pharmacokinetic parameters will be calculated:
• Actual dose (dose minus remainder in inhaler after inhalation)
• AUC0-12 (area under the curve from 0 -12 h)
• Cmax (maximum plasma concentration)
• Tmax (time to maximum plasma concentration)
• Ka absorption rate constant
• T 1/2 el terminal elimination half-life
• CL/F clearance following pulmonary administration (F= bioavailability)
Local tolerability of the inhalation of dry powder tobramycin. Both points need to have a positive result.
• Drop of FEV1 of >10% (lung function measurement)
• Adverse events
|
De volgende farmacokinetische parameters worden berekend:
• Actuele dosis (dosis min het overblijfsel in de inhaler na inhalatie)
• AUC0-12 (area under the curve van 0 -12 uur)
• Cmax (maximum plasma concentratie)
• Tmax (time to maximum plasma concentratie)
• Ka absorption rate constant
• T 1/2 el terminal elimination half-life
• CL/F clearance na pulmonale toediening (F= bioavailability)
Lokale verdraagzaamheid van de inhalatie van droog poeder tobramycine. Beide punten moeten een positief resultaat hebben:
• Afname in FEV1 van >10% (long functie meting)
• Bijwerkingen |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
within four weeks after the last test dose
|
binnen 4 weken na de laatste test dosering |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | 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 | 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 | No |
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
|
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | |