Cystic Fibrosis MedDRA version: 9.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Be male or post-menopausal/surgically sterile female (total hysterectomy and/or bilateral total ophorectomy) > 18 years old 3. Have a clinical diagnosis of cystic fibrosis with an FEV1 >40% of predicted normal 4. Be able to comply with induced sputum procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Significant portal hypertension in the opinion of the Investigator 2. Any clinically relevant disease or disorder (past or present), which in the opinion of the investigator may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient's ability to participate in the study 3. Concomitant diagnosis of significant pulmonary disease other than CF-related lung disease, including symptomatic asthma and allergic bronchopulmonary aspergillosis 4. A clinical suspicion of active or latent tuberculosis defined as any of the following: positive tuberculosis test (such as Quantiferon GOLD), and/or suspicion of active or latent tuberculosis on chest X-ray taken within last 12 months, and/or past medical history of tuberculosis 5. An acute exacerbation (defined as, an increase in respiratory symptoms requiring hospitalisation and/or a course of oral glucocorticosteroids and/or antibiotics, either prescribed or self administered); or acute respiratory infection (upper or lower) requiring oral steroids or antibiotics in the 4 weeks prior to Visit 2 6. Vaccination (killed vaccine) within 1 week before each biomarker sampling (see Table 2). For live vaccine, the limit is 4 weeks before Visit 2. Vaccination is accepted 1 week after last dose (Visit 4) 7. Acute respiratory infection with fever in the two weeks prior to Visit 2, or other acute infections requiring treatment with antibiotics, fungicides or anthelmintica in the 4 weeks before Visit 2 8. Use of oral corticosteroids in the 8 weeks prior to Visit 2 (use of inhaled corticosteroids is allowed as long as dose remains stable in the 4 weeks before Visit 2) 9. Use of antibiotics (systemic or nebuliser) in the 4 weeks prior to Visit 2 (except prophylactic treatment – acceptable if unchanged for 8 weeks prior to Visit 2), macrolides or tetracyclins not allowed 10. Treatment with any immunomodulatory agents within 8 weeks prior to Visit 2 11. Increased Cardiac Troponin I>Upper Limit of Normal (ULN) at screening (Visit 1) 12. Any clinically relevant abnormal finding in physical examination, clinical chemistry, haematology, urinalysis, vital signs or ECG at baseline, which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study 13. Patients with glomerular filtration rate less than 30 mL/min, calculated as creatinine clearance from serum-creatinine according to the Cockcroft and Gault formula: (CLcreatinine (mL/min)=constant x (140-age) x weight (kg)/serum creatinine (µM). Constant being 1.23 for men and 1.04 for women 14. Patients with underlying musculoskeletal symptoms of unknown origin and patients with shoulder girdle musculoskeletal symptoms or Dupuytrens contracture symptoms as judged by the investigator 15. Suspected or known risk of the patient transmitting HIV, hepatitis B or C via infected blood 16. Known to be infected with Burkholderia cepacia 17. Scheduled in-patient surgery or hospitalisation during the course of the study 18. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 19. Previous randomisation of treatment in the present study 20. Known or suspected hypersensitivity to study therapy or excipient of the investigational product. 21. Participation in another clinical study involving an investigational product within 12 weeks of Visit 1 If the patient participates in the genetic part of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate whether AZD1236 shows evidence of efficacy in CF patients by: • investigation of biomarkers (MMP-9 levels and TNF-a) in induced sputum • study signs and symptoms of CF compared to placebo;Secondary Objective: Secondary • To assess MMP activity (MMP-9) and other inflammatory biomarkers in sputum • To investigate the safety and tolerability of 28 days’ dosing with AZD1236 in CF patients • To investigate AZD1236 exposure in plasma and sputum • To investigate the effect of AZD1236 on inflammatory markers in blood • To investigate the effects of AZD1236 on markers of tissue degradation • To investigate the effects of AZD1236 on markers of mucus hyper-secretion;Primary end point(s): • Signs and symptoms Primary: Lung function by spirometry (FEV1, FVC, FEF25-75, IC, VC), symptom scores from BronkoTest© Diary card and Health-related quality of life (HRQL) from Cystic Fibrosis Questionnaire (CFQ-R) (Quittner et al 2000) • Biomarkers in sputum Primary: MMP-9 protein levels, differential cell count (absolute and percentage of neutrophils), inflammatory mediators (TNF-a) • Biomarkers in urine Primary: Desmosine | — |
Countries
Netherlands, Spain
Outcome results
None listed