Investigation of Efficacy, Safety and Tolerability of Once and Twice Daily Doses of AZD1981 in Asthmatic Patients

Study Overview
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Brief Summary
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The study will assess the efficacy, safety and tolerability of AZD1981 compared to non-active compound in asthmatic patients.

Official Title
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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

Conditions
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Asthma Patients

Intervention / Treatment
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* Drug: AZD1981
* Drug: AZD1981
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women. Women must be surgically sterilized/postmenopausal or use double barrier method contraception 6 months history of asthma according to ATS definition Prescribed daily dose of ICS and LABA for at least 3 months prior to Visit 2 Pre-bronchodilator FEV1 of 40 to 85 % of predicted normal A total ACQ5 score of 1.5 or more Exclusion Criteria: Respiratory infection significantly affecting the asthma Any significant disease and disorder that may put the patient at risk or influence study results Any clinically relevant abnormal findings A smoking history of more than 10 pack years Intake of oral, rectal or parenteral glucocorticosteroids

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1981 10 mg<br>AZD1981 10 mg | Drug: AZD1981<br>* AZD1981 twice daily<br>|
| Experimental: AZD1981 40 mg<br>AZD1981 40 mg | Drug: AZD1981<br>* AZD1981 twice daily<br>|
| Experimental: AZD1981 100 mg<br>AZD1981 100 mg | Drug: AZD1981<br>* AZD1981 twice daily<br>|
| Experimental: AZD1981 400 mg<br>AZD1981 400 mg | Drug: AZD1981<br>* AZD1981 twice daily<br>|
| Experimental: AZD1981 80 mg<br>AZD1981 80 mg | Drug: AZD1981<br>* AZD1981 once daily<br>|
| Experimental: AZD1981 200 mg<br>AZD1981 200 mg | Drug: AZD1981<br>* AZD1981 once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo to match AZD1981<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-bronchodilator FEV1 at the Clinic | Change from baseline: treatment period average minus baseline. Treatment period average defined as the mean of all available data during randomized treatment that occurred on or prior to treatment failure. Treatment failure defined as worsening asthma symptoms resulting in increased dose of inhaled corticosteroid. | Twelve week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morning and Evening PEF | Change from baseline: treatment period average minus baseline. Treatment period average defined as the mean of all available morning (evening) PEF during randomized treatment that occurred on or prior to treatment failure. Treatment failure defined as worsening asthma symptoms resulting in increased dose of inhaled corticosteroid. | Twelve week treatment period | 
| Asthma Control Questionnaire 5-item (ACQ5) | The ACQ5 consists of 5 questions, each assessed on a scale from 0-6, where 0 represents good asthma control and 6 represents poor asthma control. The overall score is the mean of the responses. The minimal important difference is defined as a change in score of 0.5. Change from baseline: treatment period average minus baseline. | Twelve week treatment period | 
| Adverse Events | Number of participants who had at least one adverse event during the randomized treatment period | Twelve week treatment period | 
| Number of Participants With at Least One Severe Asthma Exacerbation | Severe asthma exacerbation defined as deterioration in asthma leading to either hospitalization/emergency room treatment or oral glucocorticosteroid treatment for at least 3 days | Twelve week treatment period | 
| Number of Participants With at Least One Treatment Failure | Treatment failure is defined as a clinical need for additional inhaled corticosteroid use as judged by the investigator based on evaluations at the clinic. | Twelve week treatment period | 
| Number of Participants With Well-controlled Asthma (ACQ5<=0.75) | The ACQ5 consists of 5 questions, each assessed on a scale from 0-6, where 0 represents good asthma control and 6 represents poor asthma control. The overall score is the mean of the responses. Well-controlled asthma is defined as ACQ5<=0.75 at the end of the 12-week treatment period. | Twelve week treatment period | 
| Asthma Quality of Life Questionnaire (AQLQ(S)) | The AQLQ(S) consists of 32 questions, each assessed on a scale from 1-7, with higher values indicating better health-related quality of life. Overall scores are calculated from the means of the individual scores. The minimal important difference is a change in score of 0.5. Change from baseline: treatment period average minus baseline. | Twelve week treatment period | 
| Asthma Symptom Score | Asthma symptoms, measured in the morning and evening, based on a scale from 0-3 with higher scores indicating more severe asthma symptoms. Total asthma symptom score (0-6) is calculated by taking the sum of the morning and evening scores. Change from baseline: treatment period average minus baseline. | Twelve week treatment period | 
| Total Reliever Medication Use | Reliever medication use (number of inhalations), measured in the morning and evening. Total reliever medication use is calculated by taking the sum of the number of daytime and evening inhalations of reliever medication. Change from baseline: treatment period average minus baseline. | Twelve week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efficacy, safety, tolerability, dose finding, asthma patients