Asthma
Conditions
Keywords
Allergen Challenge, Asthma, Inhaled selective glucocorticoid receptor agonist (iSEGRA)
Brief summary
The purpose of this study is to evaluate the efficacy of AZD5423 in patients with mild asthma challenged with an inhaled allergen.
Interventions
DRUGAZD5423
Suspension for nebulisation once daily 7 days
DRUGBudesonide 200 microgram
Dry powder for inhalation twice daily 7 days
DRUGPlacebo
Solution for nebulisation once daily 7 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 18-60 years of age * Pre-bronchodilatory FEV1 ≥70% of predicted normal allergic asthmatic with a history of episodic wheeze * Positive allergen induced early and late airway bronchoconstriction showing ≥ 20% fall in FEV1 for the early and ≥ 15% for the late response * Positive skin prick test to common aeroallergens
Exclusion criteria
* Any clinically significant disease or disorder * Any clinically relevant abnormal finding at screening examinations * Smoker or ex-smoker who has stopped smoking \< 12 months prior to study start * Worsening of asthma or respiratory infection within 6 weeks from visit 1 * Allergen-specific immunotherapy within 6 months prior to visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1 | From Randomization to end of treatment | LAR was assessed on Day 6 as minimum percentage of FEV1 over 3 to 7 hours based on the analysis of the minimum percentage of FEV1 remaining over 3 to 7 hours post allergen challenge (post AC) compared to pre allergen challenge (pre AC) FEV1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge | From Randomization to end of treatment | Minimum Percentage of FEV1 over 0 to 3 hours post allergen challenge compared to pre allergen challenge FEV1 |
| Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | From Randomization to end of treatment | AUC was assessed as average percentage of FEV1 remaining 0 to 3 hours and 3 to 7 hours post allergen challenge compared to pre allergen challenge FEV1 |
| Airway Hyperresponsiveness by Assessment of Methacholine PC20 | Day 1 (pre-dose) | The methacholine challenge was performed on Day 1 (pre dose), Day 5 (\[post dose\] pre AC), and Day 7 (\[post dose\] 24 hours post AC) |
| Changes in Sputum Eosinophils Differentials (Percentage) | Day 5 (post dose) | The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 (\[post dose\] 7 hours post allergen challenge) and Day 7 (\[post dose\] 24 hours post allergen challenge) |
Countries
Canada
Participant flow
Recruitment details
Patients were enrolled from 4 centres in the AllerGen CIC group in Canada.
Pre-assignment details
Total 27 patients enrolled, 20 (74.1%) patients were randomised to receive a treatment sequence consisting of 4 different treatment in random order. From 20 randomised patients, 18 (90%) patients completed the study and 2 (10%) patients were withdrawn from the study due to consumption of disallowed medication
Participants by arm
| Arm | Count |
|---|---|
| Baseline Total Total number of patients randomised and treated in the study | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 4 - Washout | Disallowed medication | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 6 - Washout | Disallowed medication | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Baseline Total |
|---|---|
| Age, Continuous | 29.6 Years |
| Race/Ethnicity, Customized Others | 1 Participants |
| Race/Ethnicity, Customized White | 19 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 19 | 1 / 19 | 9 / 19 | 9 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 19 | 0 / 20 |
Outcome results
Primary
Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1
LAR was assessed on Day 6 as minimum percentage of FEV1 over 3 to 7 hours based on the analysis of the minimum percentage of FEV1 remaining over 3 to 7 hours post allergen challenge (post AC) compared to pre allergen challenge (pre AC) FEV1
Time frame: From Randomization to end of treatment
Population: PD Analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - 75ug AZD5423 | Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1 | 90.97 Percentage |
| Arm 2 - 300ug AZD5423 | Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1 | 91.32 Percentage |
| Arm 3 - 2x200ug Budesonide | Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1 | 87.28 Percentage |
| Arm 4 - Placebo | Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1 | 85.83 Percentage |
Secondary
Airway Hyperresponsiveness by Assessment of Methacholine PC20
The methacholine challenge was performed on Day 1 (pre dose), Day 5 (\[post dose\] pre AC), and Day 7 (\[post dose\] 24 hours post AC)
Time frame: Day 5 ([post-dose] pre allergen challenge)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - 75ug AZD5423 | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.755 mg/mL |
| Arm 2 - 300ug AZD5423 | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 2.693 mg/mL |
| Arm 3 - 2x200ug Budesonide | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 2.477 mg/mL |
| Arm 4 - Placebo | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 2.034 mg/mL |
Secondary
Airway Hyperresponsiveness by Assessment of Methacholine PC20
The methacholine challenge was performed on Day 1 (pre dose), Day 5 (\[post dose\] pre AC), and Day 7 (\[post dose\] 24 hours post AC)
Time frame: Day 1 (pre-dose)
Population: PD Analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - 75ug AZD5423 | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.560 mg/mL |
| Arm 2 - 300ug AZD5423 | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.651 mg/mL |
| Arm 3 - 2x200ug Budesonide | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.688 mg/mL |
| Arm 4 - Placebo | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.538 mg/mL |
Secondary
Airway Hyperresponsiveness by Assessment of Methacholine PC20
The methacholine challenge was performed on Day 1 (pre dose), Day 5 (\[post dose\] pre AC), and Day 7 (\[post dose\] 24 hours post AC)
Time frame: Day 7 ([post-dose] 24 hours post allergen challenge)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - 75ug AZD5423 | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 2.017 mg/mL |
| Arm 2 - 300ug AZD5423 | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 2.007 mg/mL |
| Arm 3 - 2x200ug Budesonide | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.666 mg/mL |
| Arm 4 - Placebo | Airway Hyperresponsiveness by Assessment of Methacholine PC20 | 1.214 mg/mL |
Secondary
Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge
AUC was assessed as average percentage of FEV1 remaining 0 to 3 hours and 3 to 7 hours post allergen challenge compared to pre allergen challenge FEV1
Time frame: From Randomization to end of treatment
Population: PD Analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Arm 1 - 75ug AZD5423 | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 3-7 (Average LAR) | 96.30 Percentage |
| Arm 1 - 75ug AZD5423 | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 0-3 (Average EAR) | 83.82 Percentage |
| Arm 2 - 300ug AZD5423 | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 0-3 (Average EAR) | 83.71 Percentage |
| Arm 2 - 300ug AZD5423 | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 3-7 (Average LAR) | 96.53 Percentage |
| Arm 3 - 2x200ug Budesonide | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 3-7 (Average LAR) | 93.39 Percentage |
| Arm 3 - 2x200ug Budesonide | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 0-3 (Average EAR) | 81.90 Percentage |
| Arm 4 - Placebo | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 3-7 (Average LAR) | 92.50 Percentage |
| Arm 4 - Placebo | Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge | AUC over 0-3 (Average EAR) | 82.26 Percentage |
Secondary
Changes in Sputum Eosinophils Differentials (Percentage)
The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 (\[post dose\] 7 hours post allergen challenge) and Day 7 (\[post dose\] 24 hours post allergen challenge)
Time frame: Day 7 ([post dose] 24 hours post allergen challenge)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - 75ug AZD5423 | Changes in Sputum Eosinophils Differentials (Percentage) | 0.688 Percentage | Standard Deviation 8.23 |
| Arm 2 - 300ug AZD5423 | Changes in Sputum Eosinophils Differentials (Percentage) | 2.286 Percentage | Standard Deviation 15.417 |
| Arm 3 - 2x200ug Budesonide | Changes in Sputum Eosinophils Differentials (Percentage) | 6.967 Percentage | Standard Deviation 11.697 |
| Arm 4 - Placebo | Changes in Sputum Eosinophils Differentials (Percentage) | 5.634 Percentage | Standard Deviation 5.52 |
Secondary
Changes in Sputum Eosinophils Differentials (Percentage)
The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 (\[post dose\] 7 hours post allergen challenge) and Day 7 (\[post dose\] 24 hours post allergen challenge)
Time frame: Day 5 (post dose)
Population: PD Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - 75ug AZD5423 | Changes in Sputum Eosinophils Differentials (Percentage) | 1.891 Percentage | Standard Deviation 8.375 |
| Arm 2 - 300ug AZD5423 | Changes in Sputum Eosinophils Differentials (Percentage) | -3.2 Percentage | Standard Deviation 9.162 |
| Arm 3 - 2x200ug Budesonide | Changes in Sputum Eosinophils Differentials (Percentage) | -1.825 Percentage | Standard Deviation 4.342 |
| Arm 4 - Placebo | Changes in Sputum Eosinophils Differentials (Percentage) | -0.016 Percentage | Standard Deviation 1.835 |
Secondary
Changes in Sputum Eosinophils Differentials (Percentage)
The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 (\[post dose\] 7 hours post allergen challenge) and Day 7 (\[post dose\] 24 hours post allergen challenge)
Time frame: Day 6 ([post dose] 7 hours post allergen challenge)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - 75ug AZD5423 | Changes in Sputum Eosinophils Differentials (Percentage) | 0.633 Percentage | Standard Deviation 6.011 |
| Arm 2 - 300ug AZD5423 | Changes in Sputum Eosinophils Differentials (Percentage) | 0.592 Percentage | Standard Deviation 9.658 |
| Arm 3 - 2x200ug Budesonide | Changes in Sputum Eosinophils Differentials (Percentage) | 7.500 Percentage | Standard Deviation 11.8 |
| Arm 4 - Placebo | Changes in Sputum Eosinophils Differentials (Percentage) | 12.333 Percentage | Standard Deviation 14.26 |
Secondary
Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge
Minimum Percentage of FEV1 over 0 to 3 hours post allergen challenge compared to pre allergen challenge FEV1
Time frame: From Randomization to end of treatment
Population: PD Analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - 75ug AZD5423 | Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge | 69.75 Percentage |
| Arm 2 - 300ug AZD5423 | Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge | 69.57 Percentage |
| Arm 3 - 2x200ug Budesonide | Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge | 67.98 Percentage |
| Arm 4 - Placebo | Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge | 69.30 Percentage |