A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma.
- Registration Number
- NCT01704495
- Lead Sponsor
- AstraZeneca
- Brief Summary
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
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1147
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo oral capsules self-administered twice daily AZD5069 5 mg AZD5069 AZD5069 oral capsules self-administered twice daily AZD5069 15 mg AZD5069 AZD5069 oral capsules self-administered twice daily AZD5069 45 mg AZD5069 AZD5069 oral capsules self-administered twice daily
- Primary Outcome Measures
Name Time Method Rate of Severe Asthma Exacerbations During 6 Months From start of treatment up to 6 months
- Secondary Outcome Measures
Name Time Method Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions From start of treatment up to 6 months 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 on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms From start of treatment up to 6 months Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 Baseline (Day 0) and 1 month after Day 0 Only patients with both a non-missing value at baseline and visit at one month are included in the analysis
Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score Baseline (Day 0), Treatment Period (1,3, and 6 months) 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.
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 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 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 2 Weeks Measurement of Pre-bronchodilator FEV1 Baseline (Day 0) and 2 weeks after Day 0 Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis
Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 Baseline (Day 0) and 2 months after Day 0 Only patients with both a non-missing value at baseline and visit at two months are included in the analysis
Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 Baseline (Day 0) and 3 months after Day 0 Only patients with both a non-missing value at baseline and visit at three months are included in the analysis
Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 Baseline (Day 0) and 4 months after Day 0 Only patients with both a non-missing value at baseline and visit at four months are included in the analysis
Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 Baseline (Day 0) and 6 months after Day 0 Only patients with both a non-missing value at baseline and visit at six months are included in the analysis
Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 Baseline (Day 0) and 2 weeks after Day 0 Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis
Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 Baseline (Day 0) and 2 months after Day 0 Only patients with both a non-missing value at baseline and visit at two months are included in the analysis
Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 Baseline (Day 0) and 3 months after Day 0 Only patients with both a non-missing value at baseline and visit at three months are included in the analysis
Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 Baseline (Day 0) and 4 months after Day 0 Only patients with both a non-missing value at baseline and visit at four months are included in the analysis
Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 Baseline (Day 0) and 6 months after Day 0 Only patients with both a non-missing value at baseline and visit at six months are included in the analysis
Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 Baseline (Day 0) and 1 month after Day 0 Only patients with both a non-missing value at baseline and visit at one month are included in the analysis
Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months) 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).
Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Baseline (Day 0) and 6 months after Day 0 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).
Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score Baseline (Day 0) and 6 months after Day 0 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.
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 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 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 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 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 57 to Day 84) for Use of Rescue Medication Free Days Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) Number of Well Controlled Asthma Weeks During Treatment Day 1to end of the 6 months treatment period 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 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 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 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) Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline Last 2 weeks before randomization 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 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
Trial Locations
- Locations (1)
Research Site
🇬🇧London, United Kingdom