COPD
Conditions
Keywords
COPD, Efficacy, Safety, Inhalation
Brief summary
The purpose of this study is to investigate the efficacy, safety and tolerability of 4 weeks treatment with AZD3199 in moderate to severe COPD.
Interventions
DRUGAZD3199
Dry powder for inhalation, o.d., 4 weeks
DRUGformoterol
Dry powder for inhalation, b.i.d., 4 weeks
DRUGPlacebo
Dry powder for inhalation, b.i.d., 4 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* COPD * Current or exsmokers, 10 pack years
Exclusion criteria
* Asthma * Any clinically relevant abnormal findings at screening examinations * Recent COPD exacerbation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect) | 0,5 min, 15 min, 60 min, 2 h, 4 h | change from baseline |
| FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect) | 24h, 26h | change from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Post Salbutamol Inhalation | Baseline (visit 2) and 26 h after the last morning dose (visit 5). | Mean value of FEV1 pre and post salbutamol at visit 2 and visit 5 |
| Total Number of Reliever Medication Inhalations Per 24h | During day (from rising from bed until going to bed) and night (from going to bed until rising from bed) at visit 1 to visit 5 (24h), up to 4 weeks. | Change from run-in |
| Cmax; the Highest Plasma Concentration of AZD3199 Measured | 0,15 min, 1, 4 and 24 hours post dose | PK is only measured for AZD3199 |
| Overall Mean CCQ (Clinical COPD Questionnaire) | Mean over week 0, mean over week 1, mean over week 2, and mean over week 4 | Change from baseline to treatment in score. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited). The data below represent the average of week 1,2,4 minus week 0. |
| Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD) | At baseline (visit 2) and after 4 weeks of treatment (visit 5). | The total score is calculated using all questions including their weights and scores range from 0 (perfect health) to 100 (worst possible state) |
| Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings) | Daily, during run-in and treatment | Score on a scale 5-point Likert-type scale, ranging from 0 (none) to 4 (severe) for each symptom, total score is the sum of each symptom ranged from 0 to 16. Change from run-in. |
| AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose | 0,15 min, 1, 4 and 24 hours post dose | PK is only measured for AZD3199 |
Countries
Bulgaria, Canada, Japan, Poland, Russia
Participant flow
Recruitment details
The study has been performed at 53 centres in Bulgaria, Canada, Japan, Poland and Russian Federation. The recruitment period was between 16 June 2009 and 8 January 2010.
Participants by arm
| Arm | Count |
|---|---|
| AZD3199 200 Mcg od 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening) | 65 |
| AZD3199 400 Mcg od 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening) | 69 |
| AZD3199 800 Mcg od 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening) | 65 |
| Formoterol 9 Mcg Bid 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening) | 67 |
| Placebo 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening) | 63 |
| Total | 329 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 2 | 2 | 1 |
| Overall Study | Protocol Violation | 2 | 1 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | AZD3199 200 Mcg od | AZD3199 400 Mcg od | AZD3199 800 Mcg od | Formoterol 9 Mcg Bid | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.4 Years | 63.8 Years | 65.3 Years | 64.1 Years | 64.8 Years | 63.85 Years |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 20 Participants | 16 Participants | 12 Participants | 82 Participants |
| Sex: Female, Male Male | 47 Participants | 53 Participants | 45 Participants | 51 Participants | 51 Participants | 247 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 65 | 8 / 69 | 7 / 65 | 4 / 67 | 3 / 63 |
| serious Total, serious adverse events | 1 / 65 | 4 / 69 | 0 / 65 | 3 / 67 | 2 / 63 |
Outcome results
Primary
FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect)
change from baseline
Time frame: 0,5 min, 15 min, 60 min, 2 h, 4 h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect) | 0.21 Litre | Standard Deviation 0.33 |
| AZD3199 400 Mcg od | FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect) | 0.17 Litre | Standard Deviation 0.31 |
| AZD3199 800 Mcg od | FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect) | 0.14 Litre | Standard Deviation 0.27 |
| Formoterol 9 Mcg Bid | FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect) | 0.16 Litre | Standard Deviation 0.22 |
| Placebo | FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect) | 0.03 Litre | Standard Deviation 0.25 |
Primary
FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect)
change from baseline
Time frame: 24h, 26h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect) | 0.11 Litre | Standard Deviation 0.31 |
| AZD3199 400 Mcg od | FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect) | 0.12 Litre | Standard Deviation 0.28 |
| AZD3199 800 Mcg od | FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect) | 0.11 Litre | Standard Deviation 0.25 |
| Formoterol 9 Mcg Bid | FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect) | 0.03 Litre | Standard Deviation 0.23 |
| Placebo | FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect) | 0.01 Litre | Standard Deviation 0.24 |
Secondary
AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose
PK is only measured for AZD3199
Time frame: 0,15 min, 1, 4 and 24 hours post dose
Population: AZD3199 plasma data were available for 178 of the 199 randomized patients, but data from 2 patients in AZD3199 200 mcg group were excluded from analysis because most of the values were below LOQ.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3199 200 Mcg od | AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose | 4.83 nmol*h/L |
| AZD3199 400 Mcg od | AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose | 8.69 nmol*h/L |
| AZD3199 800 Mcg od | AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose | 14.82 nmol*h/L |
Secondary
Cmax; the Highest Plasma Concentration of AZD3199 Measured
PK is only measured for AZD3199
Time frame: 0,15 min, 1, 4 and 24 hours post dose
Population: AZD3199 plasma data were available for 178 of the 199 randomized patients, but data from 2 patients in AZD3199 200 mcg group were excluded from analysis because most of the values were below LOQ.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3199 200 Mcg od | Cmax; the Highest Plasma Concentration of AZD3199 Measured | 1.14 nmol/L |
| AZD3199 400 Mcg od | Cmax; the Highest Plasma Concentration of AZD3199 Measured | 1.88 nmol/L |
| AZD3199 800 Mcg od | Cmax; the Highest Plasma Concentration of AZD3199 Measured | 4.01 nmol/L |
Secondary
FEV1 Post Salbutamol Inhalation
Mean value of FEV1 pre and post salbutamol at visit 2 and visit 5
Time frame: Baseline (visit 2) and 26 h after the last morning dose (visit 5).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | FEV1 Post Salbutamol Inhalation | 0.060 Litre | Standard Deviation 0.306 |
| AZD3199 400 Mcg od | FEV1 Post Salbutamol Inhalation | 0.073 Litre | Standard Deviation 0.358 |
| AZD3199 800 Mcg od | FEV1 Post Salbutamol Inhalation | 0.077 Litre | Standard Deviation 0.238 |
| Formoterol 9 Mcg Bid | FEV1 Post Salbutamol Inhalation | 0.048 Litre | Standard Deviation 0.26 |
| Placebo | FEV1 Post Salbutamol Inhalation | 0.018 Litre | Standard Deviation 0.215 |
Secondary
Overall Mean CCQ (Clinical COPD Questionnaire)
Change from baseline to treatment in score. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited). The data below represent the average of week 1,2,4 minus week 0.
Time frame: Mean over week 0, mean over week 1, mean over week 2, and mean over week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | Overall Mean CCQ (Clinical COPD Questionnaire) | -0.39 score on scale | Standard Deviation 0.49 |
| AZD3199 400 Mcg od | Overall Mean CCQ (Clinical COPD Questionnaire) | -0.29 score on scale | Standard Deviation 0.65 |
| AZD3199 800 Mcg od | Overall Mean CCQ (Clinical COPD Questionnaire) | -0.39 score on scale | Standard Deviation 0.54 |
| Formoterol 9 Mcg Bid | Overall Mean CCQ (Clinical COPD Questionnaire) | -0.35 score on scale | Standard Deviation 0.65 |
| Placebo | Overall Mean CCQ (Clinical COPD Questionnaire) | -0.10 score on scale | Standard Deviation 0.7 |
Secondary
Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings)
Score on a scale 5-point Likert-type scale, ranging from 0 (none) to 4 (severe) for each symptom, total score is the sum of each symptom ranged from 0 to 16. Change from run-in.
Time frame: Daily, during run-in and treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings) | -0.96 total score | Standard Deviation 1.34 |
| AZD3199 400 Mcg od | Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings) | -0.91 total score | Standard Deviation 1.65 |
| AZD3199 800 Mcg od | Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings) | -1.21 total score | Standard Deviation 1.53 |
| Formoterol 9 Mcg Bid | Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings) | -0.56 total score | Standard Deviation 1.83 |
| Placebo | Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings) | -0.43 total score | Standard Deviation 1.61 |
Secondary
Total Number of Reliever Medication Inhalations Per 24h
Change from run-in
Time frame: During day (from rising from bed until going to bed) and night (from going to bed until rising from bed) at visit 1 to visit 5 (24h), up to 4 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | Total Number of Reliever Medication Inhalations Per 24h | -0.96 Number of reliver inh. | Standard Deviation 1.85 |
| AZD3199 400 Mcg od | Total Number of Reliever Medication Inhalations Per 24h | -1.23 Number of reliver inh. | Standard Deviation 1.96 |
| AZD3199 800 Mcg od | Total Number of Reliever Medication Inhalations Per 24h | -1.15 Number of reliver inh. | Standard Deviation 1.55 |
| Formoterol 9 Mcg Bid | Total Number of Reliever Medication Inhalations Per 24h | -0.66 Number of reliver inh. | Standard Deviation 1.4 |
| Placebo | Total Number of Reliever Medication Inhalations Per 24h | -0.23 Number of reliver inh. | Standard Deviation 1.58 |
Secondary
Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD)
The total score is calculated using all questions including their weights and scores range from 0 (perfect health) to 100 (worst possible state)
Time frame: At baseline (visit 2) and after 4 weeks of treatment (visit 5).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 200 Mcg od | Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD) | -5.10 Score | Standard Deviation 13.67 |
| AZD3199 400 Mcg od | Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD) | -8.17 Score | Standard Deviation 12.18 |
| AZD3199 800 Mcg od | Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD) | -5.01 Score | Standard Deviation 10.69 |
| Formoterol 9 Mcg Bid | Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD) | -5.16 Score | Standard Deviation 10.88 |
| Placebo | Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD) | -2.35 Score | Standard Deviation 12.98 |