A double-blind, placebo-controlled, randomised, parallel-group, phase-II, multi-centre study to assess the efficacy, safety and tolerability of 4 twice daily doses and 2 once daily doses of AZD1981 given as tablets during 12 weeks in asthmatic patients treated with inhaled corticosteroids and long-acting-ß2-agonists.

• Register: EUCTR
• Last refreshed on: 27 January 2014
• Main ID: EUCTR2010-020407-73-SK
• Date of registration: 17/06/2010
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A double-blind, placebo-controlled, randomised, parallel-group, phase-II, multi-centre study to assess the efficacy, safety and tolerability of 4 twice daily doses and 2 once daily doses of AZD1981 given as tablets during 12 weeks in asthmatic patients treated with inhaled corticosteroids and long-acting-ß2-agonists.
• Scientific title: A double-blind, placebo-controlled, randomised, parallel-group, phase-II, multi-centre study to assess the efficacy, safety and tolerability of 4 twice daily doses and 2 once daily doses of AZD1981 given as tablets during 12 weeks in asthmatic patients treated with inhaled corticosteroids and long-acting-ß2-agonists.
• Date of first enrolment: 27/10/2010
• Target sample size: 1120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020407-73
• 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

Slovakia

Key inclusion & exclusion criteria

Inclusion criteria:
For inclusion in the run-in study period patients should fulfil the following criteria: 1. Provision of signed and dated informed consent prior to any study specific procedures. For patients under-age, signed and dated informed consent from both the patient´s parent/legal guardian is required.
2. Outpatients, men or women aged 18 years or above. Women must be either surgically sterilised or post-menopausal or use a highly effective method of birth control, ie, double barrier method contraception (condom and diaphragm with spermatocide or copper banded Intra Uterine Devices).
3. A minimum of 6 months documented history of asthma according to the ATS definition (1987).
4. Prescribed daily dose of ICS and LABA for at least 3 months prior to Visit 2.
5. Stable dose of ICS and LABA for the last 4 weeks prior to Visit 2. The prescribed dose of ICS and LABA must have been constant. This prescribed daily dose of ICS should be equal to or less than 500 µg of budesonide, fluticasone, ciclesonide, mometasone, HFA beclomethasone or 1000 µg CFC beclomethasone dipropionate, or other in equivalent dose.
6. Pre-bronchodilator FEV1 of 40% to 85% of predicted normal (PN) according to European Respiratory Society (ERS) guidelines.
7. Reversibility of airway obstruction according to reversibility test performed at Visit 2, defined as an increase in FEV1 =12% relative baseline after inhalation of up to 400 µg salbutamol, 360 µg albuterol or 1 mg terbutaline sulphate. (Reversibility may be repeated once prior to run-in for patients just failing to meet the reversibility criteria at Visit 2, but not later than 7 days after the initial measurement.).
8. Atopy shown by Phadiatop test.
9. Non-smokers, defined as not having smoked at more than five occasions within the previous year.
For inclusion in the pharmacogenetic research, patients must fulfil the following criterion:
10. Provision of Informed Consent for pharmacogenetic research. If a patient declines to participate in the pharmacogenetic research, there will be no consequence or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this CSP, as long as they consent to participate in the main study.
Randomisation criteria: For inclusion in the study treatment period the patients must also fulfil the following criteria at Visit 3:
11. A total ACQ5 score of 1.5 or more.
12. Pre-bronchodilator FEV1 of 40% to 85% of predicted normal (PN) according to ERS guidelines.
13. Ability to complete an eDiary correctly. Baseline diary data must be recorded for at least 8 (any 8) of the last 10 days of the run-in period.
14. Stable dose of Symbicort pMDI and no use of oral GCS during run-in.
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:
Patients should not enter the study if any of the following exclusion criteria are fulfilled
1. Respiratory infection significantly affecting the asthma, as judged by the investigator within 2 weeks prior to Visit 2.
2. Any significant disease or disorder (eg, cardiovascular, pulmonary (other than asthma), gastrointestinal, hepatic, renal, neurological, musculosceletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, either put the patient at risk because of participating in the study or may influence the results of the study, or the patients ability to participate in the study.
3. Any clinically relevant abnormal findings in clinical chemistry, haematology, urinalysis, physical examination, pulse, blood pressure or ECG at Visit 2, which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study.
4. Having a smoking history of more than 10 pack years (1 pack year = 20 cigarettes smoked per day for one year).
5. Intake of oral, rectal or parental GCS within 30 days of Visit 2.
6. Use of any ß-blockers including eye drops.
7. Known or suspected hypersensitivity to study therapy or excipients of the IP.
8. History of chronic alcohol or drug abuse or any condition associated with poor compliance as judged by the investigator.
9. Planned blood donation during the study.
10. Participation in any clinical study with an investigational drug or new formulation of a marketed drug in the 1 month prior to Visit 1
11. Planned in-patient surgery or hospitalisation during the study period.
12. Previous randomisation of treatment in the present study.
13. Involvement in the planning and conduct of the study (applies to both AstraZeneca personnel and/or study personnel at the study site).


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

Health Condition(s) or Problem(s) studied

asthma

Intervention(s)

Product Code: AZD1981
Pharmaceutical Form: Tablet
Current Sponsor code: AZD1981
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 10-100
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Symbicort pMDI
Product Name: Symbicort pMDI
Pharmaceutical Form: Pressurised inhalation, suspension
Other descriptive name: budesonide
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 80-
Other descriptive name: formoterol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 4.5-

Primary Outcome(s)

Primary end point(s): The primary variable is pre-dose pre-bronchodilator Forced Expiratory Volume in one second (FEV1) measured at the clinic.

Secondary Objective: The secondary objectives are: • To investigate the dose response relationship of AZD1981 in asthmatic patients treated with ICS and LABA. • To compare once and twice daily administration of AZD1981 in asthmatic patients treated with ICS and LABA. Safety objective: • To investigate the safety and tolerability of AZD1981 in asthmatic patients treated with ICS and LABA.

Main Objective: The primary objective is to evaluate efficacy of AZD1981 compared with placebo in asthmatic patients treated with inhaled corticosteroids (ICSs) and long-acting ß2- agonists (LABAs).

Secondary ID(s)

D9830C00008