A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma.

Study Overview
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Brief Summary
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The purpose is to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

Detailed Description
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A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study with an Optional Safety Extension Treatment Period up to 6 months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

Official Title
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A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study With an Optional Safety Extension Treatment Period up to 6 Months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients With Uncontrolled Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: AZD5069
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 years and above. Females of childbearing potential must use a highly effective contraceptive method plus a condom by their male partner. Diagnosis of asthma for at least 12 months (GINA 2011) Uncontrolled persistent asthma, despite treatment with medium to high dose ICS and LABA, and with a history of exacerbations during the last year Morning prebronchodilator FEV1 of ≥30% and ≤85% predicted normal at enrolment Daily use of medium or high dose ICS (≥fluticasone 500 µg or the equivalent daily) Exclusion Criteria: Any clinically significant disease or disorder (including any chronic lower respiratory disease other than asthma) that may put the patient at risk or influence study results Patients with recurrent, latent, or chronic infections Active tuberculosis or latent tuberculosis without completion of an appropriate course of treatment or prophylactic treatment Significant lower respiratory tract infection not resolved within 30 days prior to enrolment Current smoker or smoking history of more than 20 pack years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 150 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD5069 5 mg<br>AZD5069 oral capsules self-administered twice daily | Drug: AZD5069<br>* AZD5069 oral capsules self-administered twice daily.<br>|
| Experimental: AZD5069 15 mg<br>AZD5069 oral capsules self-administered twice daily | Drug: AZD5069<br>* AZD5069 oral capsules self-administered twice daily.<br>|
| Experimental: AZD5069 45 mg<br>AZD5069 oral capsules self-administered twice daily | Drug: AZD5069<br>* AZD5069 oral capsules self-administered twice daily.<br>|
| Placebo Comparator: Placebo<br>Placebo oral capsules self-administered twice daily | Drug: Placebo<br>* Placebo oral capsules self-administered twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Severe Asthma Exacerbations During 6 Months |  | From start of treatment up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months |  | From start of treatment up to 6 months | 
| Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions |  | From start of treatment up to 6 months | 
| Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms |  | From start of treatment up to 6 months | 
| Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis | Baseline (Day 0) and 2 weeks after Day 0 | 
| Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at one month are included in the analysis | Baseline (Day 0) and 1 month after Day 0 | 
| Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at two months are included in the analysis | Baseline (Day 0) and 2 months after Day 0 | 
| Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at three months are included in the analysis | Baseline (Day 0) and 3 months after Day 0 | 
| Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at four months are included in the analysis | Baseline (Day 0) and 4 months after Day 0 | 
| Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at six months are included in the analysis | Baseline (Day 0) and 6 months after Day 0 | 
| Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis | Baseline (Day 0) and 2 weeks after Day 0 | 
| Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at one month are included in the analysis | Baseline (Day 0) and 1 month after Day 0 | 
| Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at two months are included in the analysis | Baseline (Day 0) and 2 months after Day 0 | 
| Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at three months are included in the analysis | Baseline (Day 0) and 3 months after Day 0 | 
| Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at four months are included in the analysis | Baseline (Day 0) and 4 months after Day 0 | 
| Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 | Only patients with both a non-missing value at baseline and visit at six months are included in the analysis | Baseline (Day 0) and 6 months after Day 0 | 
| Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score | The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). | Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months) | 
| Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) | The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). | Baseline (Day 0) and 6 months after Day 0 | 
| Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score. | Baseline (Day 0), Treatment Period (1,3, and 6 months) | 
| Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score. | Baseline (Day 0) and 6 months after Day 0 | 
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | 
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56) | 
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) | 
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months) | 
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | 
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56) | 
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) | 
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months | 
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | 
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56) | 
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) | 
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days |  | Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months) | 
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms |  | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | 
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms |  | Baseline (last 14 days before randomization) and Treatment Period (Day 29 to Day 56) | 
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms |  | Baseline (last 14 days before randomization) and Treatment Period (Day 57 to Day 84) | 
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms |  | Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months) | 
| Number of Participants With Well Controlled Asthma Weeks at Baseline |  | Last 2 weeks before randomization | 
| Number of Well Controlled Asthma Weeks During Treatment |  | Day 1to end of the 6 months treatment period | 
| Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline |  | Last 2 weeks before randomization | 
| Number of Uncontrolled Persistent Asthma Weeks During Treatment |  | Day 1 to end of the 6 months treatment period | 
| Mean Plasma Concentration of AZD5069 at Day 7 |  | Day 7 | 
| Mean Plasma Concentration of AZD5069 at 1 Month |  | at 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uncontrolled Asthma,, Exacerbation,, Safety