A Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Phase II study to Assess the efficacy of 28 Day Oral Administration of AZD1236 in Adult Patients with Cystic Fibrosis. - CYBER

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2008-004699-34-NL
• Date of registration: 29/08/2008
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Phase II study to Assess the efficacy of 28 Day Oral Administration of AZD1236 in Adult Patients with Cystic Fibrosis. - CYBER
• Scientific title: A Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Phase II study to Assess the efficacy of 28 Day Oral Administration of AZD1236 in Adult Patients with Cystic Fibrosis. - CYBER
• Date of first enrolment: 28/10/2008
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004699-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Netherlands, Spain

Key inclusion & exclusion 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:
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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 9.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung

Intervention(s)

Product Code: AZD1236
Pharmaceutical Form: Tablet
Current Sponsor code: AZD1236
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

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 ID(s)

D4260C00008