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 Bronchiectasis

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000753-35-GB
• Date of registration: 11/04/2008
• 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 Bronchiectasis
• 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 Bronchiectasis
• Date of first enrolment: 20/02/2009
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000753-35
• 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, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent prior to any study specific procedures

2. Male or female of non-child bearing potential (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), between 18 and 80 years

3. Have a clinical diagnosis of idiopathic or post infective bronchiectasis as diagnosed with a historical high resolution computerised tomography (HRCT) or bronchogram

4. Be sputum producers with a history of chronic expectoration on most days of most weeks of the year. Patients should have a history of spontaneously producing an average of 3 ml or more sputum on a daily basis and should be able to provide at least 2 of the 3 required baseline sputum samples

5. Have normal laboratory values at Visit 1, unless the investigator considers an abnormality to be clinically irrelevant

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. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

2. Previous randomization 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. Bronchiectasis associated with a generalised immunodeficiency disorder, where manifestations other than bronchiectasis predominate

5. Concomitant diagnosis of significant pulmonary disease other than bronchiectasis or COPD, including symptomatic asthma and allergic bronchopulmonary aspergillosis

6. An FEV1 of <30% of predicted normal at Visit 1

7. Any ECG abnormality at Visit 1 (including a QTc interval of >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 study assessments.

8. 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

9. Other acute infections requiring treatment in the 4 weeks prior to Visit 2

10. Use of prohibited medications as detailed in Section 6.5 of the Protocol

11. A past history of or current clinical or laboratory evidence of renal disease, or a calculated creatinine clearance (Cockcroft-Gault formula) of =70 ml/min at Visit 1

12. Any other clinical disease or disorder (including insulin dependent diabetes) 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

13. History of excessive alcohol consumption or chronic alcohol induced disease

14. Donation of >1350 mL of blood in the 12 months or 500 mL of blood in the 3 months before the end of the study

15. Suspected or known risk of the patient transmitting HIV, Hepatitis B or C

16. 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

Bronchiectasis
MedDRA version: 9.1 Level: LLT Classification code 10006445 Term: Bronchiectasis

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)

Main Objective: To investigate whether AZD9668 shows evidence of efficacy in bronchiectasis patients by investigation of:

· Absolute and percentage neutrophil cell count in the sputum
· Signs and symptoms of bronchiectasis (including effects on quality of life)

Secondary Objective: · To investigate the effect of AZD9668 on Neutrophil Elastase (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 bronchiectasis patients

· To confirm AZD9668 exposure in plasma and in spontaneously produced sputum

· To investigate the effect of AZD9668 on urine desmosine (marker of tissue degradation)

Primary end point(s): Absolute and percentage neutrophil cell count in sputum

Bronkotest © diary card

24 hour sputum collection weight

St George’s Respiratory Questionnaire

Lung function tests

Secondary ID(s)

D0520C00010