E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary ciliary dyskinesia (PCD) |
|
E.1.1.1 | Medical condition in easily understood language |
Primary ciliary dyskinesia |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10069713 |
E.1.2 | Term | Primary ciliary dyskinesia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 determine the efficacy of 6 months of maintenance treatment with azithromycin on respiratory system exacerbations in subjects with Primary ciliary dyskinesia, 7-50 years of age. |
|
E.2.2 | Secondary objectives of the trial |
•To determine the efficacy of azithromycin on FEV1, FVC and FEF25-75; •To determine the efficacy of azithromycin on Intra Thoracic Gas Volume (ITGV) and airways resistance; •To determine the efficacy of azithromycin on the new outcome measure: Lung Clearance Index (LCI); •To determine the efficacy of azithromycin on Respiratory symptoms, Sinus symptoms and Ear & Hearing symptoms on the Quality Of Life – Primary ciliary dyskinesia measure (QOL-PCD); •To determine the efficacy of azithromycin on hearing impairment; •To determine the efficacy of azithromycin on sputum microbiology and inflammatory markers; •To assess the safety of azithromycin.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A confirmed diagnosis of PCD: - Characteristic clinical symptoms; and - High speed video microscopic recordings of abnormal ciliary beat pattern and/or frequency; and: either - Abnormally low nasal NO production < 77 nl/min; and/or - Abnormal ciliary ultra-structure demonstrated by transmission electron microscopy analysis or high resolution immunofluorescence (not incl. isolated IDA); and/or - An unequivocal genetic mutation recognized to cause PCD.
• Age ≥ 7 years and < 50 years at inclusion;
• Ability to swallow tablets;
• At least 30 days treatment with antibiotics prescribed against respiratory tract infections/pulmonary exacerbations in the previous 2 years;
• No AZN treatment within 1 month prior to screening (visit 1);
• No current therapy with systemic or inhaled maintenance antibiotics;
• FEV1 % predicted > 40 % at screening (Visit 1);
• Ability to perform spirometry and Multiple Breath Washout (MBW);
• Personally provide, or have a legal guardian provide written informed consent to participate in the trial, according to local regulations.
|
|
E.4 | Principal exclusion criteria |
• Known infection with Nontuberculous Mycobacteria (NTM) (found in sputum in the past 6 months prior to screening (Visit 1), Achromobacter xylosoxidans, Burkholderia cepacia or chronic infection with Pseudomonas aeruginosa;
• Be currently participating in, or have participated in another investigative drug trial within four weeks prior of screening (Visit 1);
• A history of allergic reaction to macrolide antibiotics incl. ketolide antibiotics, peanut, or to any of the excipients of ‘Azithromycine CF 250 mg’ or to any of the ingredients of the placebo (Carboxymethylstarch sodium, Cellulose microcryst. (PH 102), Colloidal anhydrous silica, Gelatin, Glycerol distearate, Lactose monohydrate, Magnesium stearate, Microcrystalline cellulose, Polyvinyl alcohol, Potato starch, Pregelatinised maize starch, Sodium laurilsulfate, Sodium starch glycolate, Soya lecithin, Talc, Titanium dioxide (E171) and Xanthan gum);
• Liver disease with Alanine transaminase (ALT) twice or more the upper limits of normal or history of portal hypertension ;
• Known kidney disease with serum creatinine > 150 µmol/l and/or Glomerular Filtration Rate (GFR) < 50 ml/min;
• Known congenital or documented acquired prolonged QT-interval, cardiac arrhythmia, clinical relevant bradycardia, severe heart failure, or electrolyte disturbances.
• Known myasthenia gravis.
• Current treatment with ciclosporin, coumarin-like oral anticoagulants (e.g. warfarin), digoxin, ergotamine derivatives (e.g. methylergometrine), nelfinavir, rifabutin and active substances known to prolong QT interval such as amiodarone and other class ΙA and class ΙΙΙ antiarrhythmics, cisapride, terfenadin, antipsychotic agents such as pimozide, antidepressants such as citalopram and fluoroquinolones such as moxifloxacin and levofloxacin;
• Be pregnant or breastfeeding; plan to become pregnant whilst in the trial; or be female of childbearing potential (at the discretion of the investigator) using an unreliable form of contraception;
• Requirement of home oxygen (not incl. supplemental oxygen for use only when exercising, mountaineering or travelling by air) or assisted ventilation; or • Have any concomitant medical, psychiatric, or social condition that, in the Investigator’s opinion, would put the subject at significant risk, may confound the results or may significantly interfere with the subject’s participation in the trial.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Difference in the number of respiratory system exacerbations between treatments in the pre- to post-intervention period.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Difference in FEV1 % predicted, FVC % predicted and FEF25-75 % predicted between treatments in the pre- to post-intervention period.
• Difference in RV % predicted, RV/TLC % predicted and Raw % predicted between treatments in the pre- to post-intervention period.
• Difference in Lung Clearance Index (LCI), Sacin and Scond between treatments in the pre- to post-intervention period.
• Difference in Respiratory symptoms, Sinus symptoms and Ear & Hearing symptoms on the QOL-PCD between treatments in the pre- to post-intervention period.
• Difference in hearing threshold between treatments in the pre- to post-intervention period.
• Difference in tympanometry between treatments in the pre- to post-intervention period.
• Difference in inflammatory markers between treatments in the pre- to post-intervention period.
• Difference in sputum microbiology between treatments in the pre- to post-intervention period.
• Adverse Events (AE) and Serious Adverse Events (SAE). |
|
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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
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 | No |
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 |
|
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
|
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |