A Phase II, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy of 28 Day Oral Administration of AZD9668 in Patients with Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-001530-27-GB
• Date of registration: 18/04/2008
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A Phase II, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy of 28 Day Oral Administration of AZD9668 in Patients with Cystic Fibrosis
• Scientific title: A Phase II, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy of 28 Day Oral Administration of AZD9668 in Patients with Cystic Fibrosis
• Date of first enrolment: 11/03/2009
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001530-27
• 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

Denmark, Germany, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
For inclusion in the study patients must fulfil the following criteria:
1. Provision of informed consent/assent prior to any study specific procedures
2. Male or post-menopausal/surgically sterile female (defined as amenorrhoeic for 12 months and follicle stimulating hormone (FSH) plasma concentration within the post-menopausal range as defined by the laboratory) or surgically sterile (defined as having undergone bilateral oophrectomy and/or hysterectomy; tubal ligation on its own is not adequate), aged =16 years
3. Have a clinical diagnosis of CF with a FEV1 =40%
4. Have normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant
5. Have normal renal function, defined as calculated glomerular filtration rate of >70 mL/min (as calculated by the Cockcroft-Gault formula) unless the investigator considers an abnormality to be clinically irrelevant.

Are the trial subjects under 18? yes
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:
Patients must not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca/delegate staff and/or staff at the study site)
2. Previous randomisation of treatment in the present study
3. 'Participation (defined as administration of at least one dose of investigational product) in another clinical study within 12 weeks of Visit 1
4. Significant liver disease
5. Alanine aminotransferase / aspartate aminotransferase (AST) level = 1.5 x ULN at Visit 1
6. Any other non-CF-related lung disease that may interfere with study assessments, in the opinion of the investigator
7. 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 6 weeks prior to Visit 2
8. Other acute infections requiring treatment in the 4 weeks prior to Visit 2
9. Lung transplant patients
10. Any ECG abnormality (including a QTc > 450 msec for males and > 470 msec for females, or any arrhythmia) which in the opinion of the investigator may put the patient at risk or interfere with the study assessments
11. Use of prohibited medications as detailed in Section 6.5
12. Patients using percutaneous intravenous catheters
13. Known to be infected with Burkholderia cepacia complex
14. Any other clinical disease or disorder, which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study
15. History of excessive alcohol consumption or chronic alcohol induced disease
16. Donation of >1350 mL of blood in the 12 months or 500 mL of blood in the 3 months before Visit 2
17. Suspected or known risk of the patient transmitting human immunodeficiency virus, hepatitis B or C
18. Scheduled in-patient surgery or hospitalisation during the course of the study



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 10011762 Term: Cystic fibrosis

Intervention(s)

Product Name: AZD9668
Product Code: AZD9668
Pharmaceutical Form: Tablet
INN or Proposed INN: none
CAS Number: none
Current Sponsor code: AZD9668
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): - Absolute and differential neutrophil cell count in sputum
- Lung function (FEV1, slow vital capacity (SVC) forced vital capacity [FVC], forced expiratory flow between 25 and 75% of forced vital capacity [FEF25-75])
- Weight of 24 hour sputum collection (pre-treatment versus end of treatment)
- Symptom scores from diary card (BronkoTest© diary)
- Quality of Life (Quittner questionnaire)

Secondary Objective: The secondary objectives are:
- To investigate the effect of AZD9668 on NE activity in sputum
- To investigate the effect of AZD9668 on other inflammatory markers in sputum
- To investigate the effect of AZD9668 on inflammatory markers in blood
- To investigate the safety and tolerability of 28 days’ dosing with AZD9668 in CF patients
- To confirm AZD9668 exposure in plasma and induced sputum
- To investigate the effect of AZD9668 on urine desmosine (marker of tissue degradation).

An optional objective in this study is to collect samples for possible retrospective pharmacogenetic analysis to investigate the influence of genotype on pharmacokinetics (and pharmacodynamic response where appropriate). The results of the pharmacogenetic analysis will be reported separately from the main Clinical Study Report (CSR).

Main Objective: The primary objective is to investigate whether AZD9668 shows evidence of efficacy in CF patients by investigation of:
- Absolute and differential neutrophil count in induced sputum.
- Signs and symptoms of CF (including effects on QoL)

Secondary ID(s)

D0520C00009