Bronchiectasis
Conditions
Keywords
bronchiectasis, Phase II
Brief summary
The purpose of this study is to investigate if treatment with AZD9668 for 28 days is effective in treating Bronchiectasis (Brx) and if so how it compares to placebo (a substance which does not have any action).
Interventions
DRUGAZD9668
2 x 30 mg, oral tablet, twice daily for 28 days
DRUGPlacebo
2 x Matched placebo, oral tablet, twice daily for 28 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Female of non child bearing potential * Clinical diagnosis of bronchiectasis * Be sputum producers, with history of chronic expectoration on most days
Exclusion criteria
* Concomitant diagnosis of pulmonary disease other than bronchiectasis or COPD * FEV1 of \<30% of predicted normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) | Baseline and day 28 | SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). Change from baseline to day 28. |
| Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| 24-hour Sputum Weight(g) | Baseline and day 28 | Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28 |
| Slow Vital Capacity (SVC) | Baseline and day 28 | Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28 |
| Forced Expiratory Volume in 1 Second (FEV1) | Baseline and day 28 | Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28 |
| Forced Vital Capacity (FVC) | Baseline and day 28 | Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28 |
| Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | Baseline and day 28 | FEF25-75% as a measure of lung function.Change from baseline to day 28 |
| Morning Peak Expiratory Flow (PEF) | Last 7 days on treatment | Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment |
| Evening Peak Expiratory Flow (PEF) | Last 7 days on treatment | Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment |
| Bronkotest Diary Card Signs and Symptoms | Last 7 days on treatment | The Bronkotest diary card includes 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). ANOVA models were fitted to compare the change from baseline between AZD9668 and placebo for each question separately, with a p-value of 0.1 considered statistically significant. The number of number of these 8 measures with significant differences is reported. |
| Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
| Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline | Baseline and day 28 | Ratio of day 28 to baseline |
| Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline | Baseline and day 28 | Ratio of day 28 to baseline |
| Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits |
Countries
Canada, United Kingdom
Participant flow
Recruitment details
First patient enrolled 25 September 2008. Last patient completed 20 April 2009. Study conducted at 6 centres in Canada and 4 centres in the UK.
Participants by arm
| Arm | Count |
|---|---|
| AZD9668 AZD9668, 2 x 30 mg twice daily (bid) | 22 |
| Placebo Placebo, 2 tablets twice daily (bid) | 16 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Disallowed medication | 1 | 0 |
| Overall Study | Voluntary discontinuation | 0 | 2 |
Baseline characteristics
| Characteristic | AZD9668 | Placebo | Total |
|---|---|---|---|
| Age Continuous | 61 years | 62 years | 62 years |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 13 Participants | 5 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 22 | 15 / 16 |
| serious Total, serious adverse events | 0 / 22 | 0 / 16 |
Outcome results
Primary
24-hour Sputum Weight(g)
Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | 24-hour Sputum Weight(g) | -0.15 g | Standard Error 4.376 |
| Placebo | 24-hour Sputum Weight(g) | -5.37 g | Standard Error 3.455 |
Primary
Bronkotest Diary Card Signs and Symptoms
The Bronkotest diary card includes 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). ANOVA models were fitted to compare the change from baseline between AZD9668 and placebo for each question separately, with a p-value of 0.1 considered statistically significant. The number of number of these 8 measures with significant differences is reported.
Time frame: Last 7 days on treatment
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD9668 | Bronkotest Diary Card Signs and Symptoms | 0 events |
| Placebo | Bronkotest Diary Card Signs and Symptoms | 0 events |
Primary
Evening Peak Expiratory Flow (PEF)
Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment
Time frame: Last 7 days on treatment
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Evening Peak Expiratory Flow (PEF) | 4.56 L/min | Standard Error 6.352 |
| Placebo | Evening Peak Expiratory Flow (PEF) | -1.15 L/min | Standard Error 7.399 |
Primary
Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
FEF25-75% as a measure of lung function.Change from baseline to day 28
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | 0.08 L/s | Standard Error 0.031 |
| Placebo | Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | 0.01 L/s | Standard Error 0.038 |
Primary
Forced Expiratory Volume in 1 Second (FEV1)
Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Forced Expiratory Volume in 1 Second (FEV1) | 0.06 L | Standard Error 0.021 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) | -0.04 L | Standard Error 0.026 |
Primary
Forced Vital Capacity (FVC)
Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Forced Vital Capacity (FVC) | 0.03 L | Standard Error 0.048 |
| Placebo | Forced Vital Capacity (FVC) | 0.00 L | Standard Error 0.061 |
Primary
Morning Peak Expiratory Flow (PEF)
Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment
Time frame: Last 7 days on treatment
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Morning Peak Expiratory Flow (PEF) | 4.06 L/min | Standard Error 6.168 |
| Placebo | Morning Peak Expiratory Flow (PEF) | -4.98 L/min | Standard Error 7.174 |
Primary
Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline | 1.08 ratio |
| Placebo | Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline | 1.01 ratio |
Primary
Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline | 1.12 ratio |
| Placebo | Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline | 1.04 ratio |
Primary
Slow Vital Capacity (SVC)
Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Slow Vital Capacity (SVC) | 0.07 L | Standard Error 0.045 |
| Placebo | Slow Vital Capacity (SVC) | -0.07 L | Standard Error 0.057 |
Primary
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). Change from baseline to day 28.
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) | -7.39 Scores on a scale | Standard Error 3.764 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) | -1.137 Scores on a scale | Standard Error 4.608 |
Secondary
Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | 0.74 ratio |
| Placebo | Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | 0.93 ratio |
Secondary
Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | 0.70 ratio |
| Placebo | Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | 0.98 ratio |
Secondary
Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | 0.91 ratio |
| Placebo | Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | 1.06 ratio |
Secondary
Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | 0.83 ratio |
| Placebo | Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | 0.91 ratio |
Secondary
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | 0.79 ratio |
| Placebo | Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | 1.07 ratio |
Secondary
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | 0.73 ratio |
| Placebo | Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | 1.15 ratio |
Secondary
Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | 0.93 ratio |
| Placebo | Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | 1.00 ratio |
Secondary
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 0.98 ratio |
| Placebo | Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 0.96 ratio |
Secondary
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Time frame: Baseline and day 28
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 0.96 ratio |
| Placebo | Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 1.05 ratio |