Trial Outcomes & Findings for A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis (NCT NCT00769119)
NCT ID: NCT00769119
Last Updated: 2012-08-20
Results Overview
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
COMPLETED
PHASE2
38 participants
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
2012-08-20
Participant Flow
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.
Participant milestones
| Measure |
AZD9668
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
16
|
|
Overall Study
COMPLETED
|
20
|
13
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
AZD9668
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Overall Study
Voluntary discontinuation
|
0
|
2
|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Disallowed medication
|
1
|
0
|
Baseline Characteristics
A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis
Baseline characteristics by cohort
| Measure |
AZD9668
n=22 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=16 Participants
Placebo, 2 tablets twice daily (bid)
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
61 years
n=93 Participants
|
62 years
n=4 Participants
|
62 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=18 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=10 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline
|
1.08 ratio
Interval 0.6 to 1.72
|
1.01 ratio
Interval 0.73 to 1.6
|
PRIMARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=18 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=10 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline
|
1.12 ratio
Interval 1.02 to 1.21
|
1.04 ratio
Interval 0.92 to 1.16
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: 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.
Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=13 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
24-hour Sputum Weight(g)
|
-0.15 g
Standard Error 4.376 • Interval 4.376 to
|
-5.37 g
Standard Error 3.455 • Interval 3.455 to
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: 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.
Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=13 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Slow Vital Capacity (SVC)
|
0.07 L
Standard Error 0.045 • Interval 0.045 to
|
-0.07 L
Standard Error 0.057 • Interval 0.057 to
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: 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.
Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=13 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1)
|
0.06 L
Standard Error 0.021 • Interval 0.021 to
|
-0.04 L
Standard Error 0.026 • Interval 0.026 to
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: 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.
Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=13 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Forced Vital Capacity (FVC)
|
0.03 L
Standard Error 0.048 • Interval 0.048 to
|
0.00 L
Standard Error 0.061 • Interval 0.061 to
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: 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.
FEF25-75% as a measure of lung function.Change from baseline to day 28
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=13 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
|
0.08 L/s
Standard Error 0.031 • Interval 0.031 to
|
0.01 L/s
Standard Error 0.038 • Interval 0.038 to
|
PRIMARY outcome
Timeframe: Last 7 days on treatmentPopulation: 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.
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
Outcome measures
| Measure |
AZD9668
n=21 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=16 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Morning Peak Expiratory Flow (PEF)
|
4.06 L/min
Standard Error 6.168 • Interval 6.168 to
|
-4.98 L/min
Standard Error 7.174 • Interval 7.174 to
|
PRIMARY outcome
Timeframe: Last 7 days on treatmentPopulation: 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.
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
Outcome measures
| Measure |
AZD9668
n=21 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=16 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Evening Peak Expiratory Flow (PEF)
|
4.56 L/min
Standard Error 6.352 • Interval 6.352 to
|
-1.15 L/min
Standard Error 7.399 • Interval 7.399 to
|
PRIMARY outcome
Timeframe: Last 7 days on treatmentPopulation: 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.
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.
Outcome measures
| Measure |
AZD9668
n=21 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=16 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Bronkotest Diary Card Signs and Symptoms
|
0 events
|
0 events
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: 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.
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.
Outcome measures
| Measure |
AZD9668
n=19 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=13 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
|
-7.39 Scores on a scale
Standard Error 3.764 • Interval 3.764 to
|
-1.137 Scores on a scale
Standard Error 4.608 • Interval 4.608 to
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
|
0.93 ratio
Interval 0.66 to 1.3
|
1.00 ratio
Interval 0.64 to 1.55
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
|
0.70 ratio
Interval 0.58 to 0.86
|
0.98 ratio
Interval 0.75 to 1.28
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=11 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
|
0.74 ratio
Interval 0.52 to 1.07
|
0.93 ratio
Interval 0.57 to 1.53
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
|
0.73 ratio
Interval 0.6 to 0.88
|
1.15 ratio
Interval 0.9 to 1.48
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
|
0.79 ratio
Interval 0.62 to 1.01
|
1.07 ratio
Interval 0.78 to 1.47
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
|
0.91 ratio
Interval 0.67 to 1.23
|
1.06 ratio
Interval 0.71 to 1.58
|
SECONDARY outcome
Timeframe: 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.
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
|
0.83 ratio
Interval 0.64 to 1.09
|
0.91 ratio
Interval 0.64 to 1.3
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: 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.
Ratio of day 28 to baseline
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
|
0.98 ratio
Interval 0.92 to 1.05
|
0.96 ratio
Interval 0.88 to 1.05
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: 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.
Ratio of day 28 to baseline
Outcome measures
| Measure |
AZD9668
n=20 Participants
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=12 Participants
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
|
0.96 ratio
Interval 0.83 to 1.11
|
1.05 ratio
Interval 0.87 to 1.26
|
Adverse Events
AZD9668
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AZD9668
n=22 participants at risk
AZD9668, 2 x 30 mg twice daily (bid)
|
Placebo
n=16 participants at risk
Placebo, 2 tablets twice daily (bid)
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/22
|
12.5%
2/16
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.00%
0/22
|
6.2%
1/16
|
|
Cardiac disorders
Palpitations
|
0.00%
0/22
|
6.2%
1/16
|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
2/22
|
25.0%
4/16
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/22
|
6.2%
1/16
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
4.5%
1/22
|
6.2%
1/16
|
|
Gastrointestinal disorders
Nausea
|
4.5%
1/22
|
6.2%
1/16
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
1/22
|
6.2%
1/16
|
|
General disorders
Oedema Peripheral
|
4.5%
1/22
|
12.5%
2/16
|
|
General disorders
Chest Discomfort
|
0.00%
0/22
|
6.2%
1/16
|
|
General disorders
Fatigue
|
0.00%
0/22
|
6.2%
1/16
|
|
General disorders
Local Swelling
|
0.00%
0/22
|
6.2%
1/16
|
|
Infections and infestations
Nasopharyngitis
|
18.2%
4/22
|
0.00%
0/16
|
|
Infections and infestations
Influenza
|
0.00%
0/22
|
6.2%
1/16
|
|
Infections and infestations
Sinusitis
|
0.00%
0/22
|
6.2%
1/16
|
|
Injury, poisoning and procedural complications
Contusion
|
9.1%
2/22
|
6.2%
1/16
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/22
|
6.2%
1/16
|
|
Injury, poisoning and procedural complications
Thermal Burn
|
0.00%
0/22
|
6.2%
1/16
|
|
Metabolism and nutrition disorders
Increased Appetite
|
0.00%
0/22
|
6.2%
1/16
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
2/22
|
0.00%
0/16
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
9.1%
2/22
|
6.2%
1/16
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
4.5%
1/22
|
6.2%
1/16
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/22
|
6.2%
1/16
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Discomfort
|
0.00%
0/22
|
6.2%
1/16
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/22
|
6.2%
1/16
|
|
Nervous system disorders
Headache
|
31.8%
7/22
|
18.8%
3/16
|
|
Nervous system disorders
Dizziness
|
0.00%
0/22
|
6.2%
1/16
|
|
Nervous system disorders
Lethargy
|
4.5%
1/22
|
6.2%
1/16
|
|
Nervous system disorders
Tremor
|
0.00%
0/22
|
6.2%
1/16
|
|
Psychiatric disorders
Depressed Mood
|
0.00%
0/22
|
6.2%
1/16
|
|
Psychiatric disorders
Sleep Disorder
|
0.00%
0/22
|
6.2%
1/16
|
|
Reproductive system and breast disorders
Erectile Dysfunction
|
0.00%
0/22
|
6.2%
1/16
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/22
|
12.5%
2/16
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/22
|
6.2%
1/16
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.5%
1/22
|
6.2%
1/16
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
4.5%
1/22
|
6.2%
1/16
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
0.00%
0/22
|
6.2%
1/16
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/22
|
6.2%
1/16
|
|
Vascular disorders
Hyperaemia
|
0.00%
0/22
|
6.2%
1/16
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place