Trial Outcomes & Findings for One Month Dose Response Study of AZD1981 in Asthma Patients Uncontrolled on Inhaled Steroids (NCT NCT00758589)

NCT ID: NCT00758589

Last Updated: 2014-02-26

Results Overview

Mean mPEF during the treatment period (mean of the last 2 weeks of the treatment period)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

368 participants

Primary outcome timeframe

Week 4

Results posted on

2014-02-26

Participant Flow

510 patients enrolled, 368 were allocated to treatment and 350 completed the study. First patient entered the study on 16 September 2008 and the last patient finished the study on 13 July 2009.

Participant milestones

Participant milestones
Measure
AZD1981 50 mg Twice Daily (Bid)
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
AZD1981 oral tablet 1000 mg, twice daily
Placebo
placebo oral tablet, twice daily
Overall Study
STARTED
95
90
92
91
Overall Study
COMPLETED
92
87
86
85
Overall Study
NOT COMPLETED
3
3
6
6

Reasons for withdrawal

Reasons for withdrawal
Measure
AZD1981 50 mg Twice Daily (Bid)
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
AZD1981 oral tablet 1000 mg, twice daily
Placebo
placebo oral tablet, twice daily
Overall Study
Adverse Event
3
2
5
4
Overall Study
Withdrawal by Subject
0
1
1
1
Overall Study
Palm stopped to work
0
0
0
1

Baseline Characteristics

One Month Dose Response Study of AZD1981 in Asthma Patients Uncontrolled on Inhaled Steroids

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Total
n=368 Participants
Total of all reporting groups
Age, Continuous
43.3 Years
n=5 Participants
43 Years
n=7 Participants
43.5 Years
n=5 Participants
45.7 Years
n=4 Participants
44.35 Years
n=21 Participants
Sex: Female, Male
Female
27 Participants
n=5 Participants
19 Participants
n=7 Participants
34 Participants
n=5 Participants
33 Participants
n=4 Participants
113 Participants
n=21 Participants
Sex: Female, Male
Male
68 Participants
n=5 Participants
71 Participants
n=7 Participants
58 Participants
n=5 Participants
58 Participants
n=4 Participants
255 Participants
n=21 Participants

PRIMARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean mPEF during the treatment period (mean of the last 2 weeks of the treatment period)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=89 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=90 Participants
placebo oral tablet, twice daily
Morning Peak Expiratory Flow (mPEF)
346.42 L/min
Standard Deviation 132.70 • Interval -245.0 to 334.0
362.54 L/min
Standard Deviation 134.69 • Interval -131.0 to 213.0
352.87 L/min
Standard Deviation 124.22 • Interval -158.0 to 219.0
329.75 L/min
Standard Deviation 140.14 • Interval -283.0 to 158.0

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean ePEF during the treatment period (mean of the last 2 weeks of the treatment period)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=89 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Evening Peak Expiratory Flow (ePEF)
359.83 L/min
Standard Deviation 129.23 • Interval -192.0 to 315.0
378.98 L/min
Standard Deviation 134.54 • Interval -179.0 to 262.0
368.70 L/min
Standard Deviation 124.08 • Interval -149.0 to 225.0
348.87 L/min
Standard Deviation 142.92 • Interval -202.0 to 197.0

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean mFEV1 during the treatment period (mean of the last 2 weeks of the treatment period)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=67 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=63 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=71 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=71 Participants
placebo oral tablet, twice daily
Morning Forced Expiratory Volume in 1 Second (mFEV1)
2.45 L
Standard Deviation 0.99 • Interval -1.24 to 1.8
2.65 L
Standard Deviation 1.03 • Interval -1.41 to 1.04
2.53 L
Standard Deviation 0.97 • Interval -0.503 to 0.843
2.31 L
Standard Deviation 1.05 • Interval -2.21 to 1.12

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean eFEV1 during the treatment period (mean of the last 2 weeks of the treatment period)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=66 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=66 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=73 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=72 Participants
placebo oral tablet, twice daily
Evening Forced Expiratory Volume in 1 Second (eFEV1)
2.47 L
Standard Deviation 0.95 • Interval -0.834 to 1.17
2.72 L
Standard Deviation 1.02 • Interval -1.56 to 1.2
2.63 L
Standard Deviation 0.98 • Interval -0.765 to 2.03
2.43 L
Standard Deviation 1.06 • Interval -1.46 to 1.66

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean total reliever use during the treatment period (mean of the last 2 weeks of the treatment period)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Total Use of Reliever
2.870 Number of inhalations per day
Standard Deviation 2.475 • Interval -4.8 to 5.34
2.640 Number of inhalations per day
Standard Deviation 2.303 • Interval -6.36 to 6.59
2.569 Number of inhalations per day
Standard Deviation 2.210 • Interval -8.3 to 3.23
2.855 Number of inhalations per day
Standard Deviation 2.430 • Interval -6.79 to 2.84

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean night-time asthma symptom score during the treatment period (mean of the last 2 weeks of the treatment period). Scores range from 0 (none) to 3 (bad).

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Night-time Asthma Symptom Score
0.998 Scores on a scale
Standard Deviation 0.633 • Interval -2.8 to 0.733
0.881 Scores on a scale
Standard Deviation 0.543 • Interval -1.36 to 0.786
0.912 Scores on a scale
Standard Deviation 0.594 • Interval -1.83 to 0.655
1.008 Scores on a scale
Standard Deviation 0.614 • Interval -2.12 to 0.714

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean day-time asthma symptom score during the treatment period (mean of the last 2 weeks of the treatment period). Scores range from 0 (none) to 3 (bad).

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Day-time Asthma Symptom Score
1.037 Scores on a scale
Standard Deviation 0.609 • Interval -2.8 to 0.85
0.933 Scores on a scale
Standard Deviation 0.556 • Interval -1.0 to 1.04
0.995 Scores on a scale
Standard Deviation 0.552 • Interval -2.2 to 1.25
1.105 Scores on a scale
Standard Deviation 0.645 • Interval -2.0 to 1.62

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean percentage of awakenings due to asthma symptoms during the treatment period (mean of the last 2 weeks of the treatment period)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Awakenings
38.59 Percentage of days
Standard Deviation 40.25 • Interval -100.0 to 44.4
33.18 Percentage of days
Standard Deviation 38.93 • Interval -84.6 to 100.0
33.34 Percentage of days
Standard Deviation 37.68 • Interval -92.3 to 60.0
37.32 Percentage of days
Standard Deviation 39.51 • Interval -100.0 to 58.6

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean percentage of asthma control days during the treatment period (mean of the last 2 weeks of the treatment period). An asthma control day is defined as a symptom-free day with no use of reliever medication during day and night. A symptom-free day is defined as a day and a night with no asthma symptoms and a day and night with no awakenings due to asthma symptoms.

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Asthma Control Day
10.78 Percentage of days
Standard Deviation 25.79 • Interval -12.5 to 100.0
7.48 Percentage of days
Standard Deviation 20.71 • Interval -20.0 to 100.0
13.23 Percentage of days
Standard Deviation 26.24 • Interval -38.3 to 100.0
10.08 Percentage of days
Standard Deviation 22.36 • Interval -1.67 to 100.0

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean percentage of symptom free days during the treatment period (mean of the last 2 weeks of the treatment period). A symptom-free day is defined as a day and a night with no asthma symptoms and a day and night with no awakenings due to asthma symptoms.

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Symptom Free Day
17.33 Percentage of days
Standard Deviation 32.16 • Interval -49.2 to 100.0
13.95 Percentage of days
Standard Deviation 28.35 • Interval -52.3 to 100.0
15.56 Percentage of days
Standard Deviation 28.51 • Interval -72.3 to 100.0
14.31 Percentage of days
Standard Deviation 26.28 • Interval -23.8 to 100.0

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean percentage of reliever free days during the treatment period (mean of the last 2 weeks of the treatment period). A reliever free day is defined as a day and a night with no use of as-needed medication.

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Reliever Free Day
22.59 Percentage of days
Standard Deviation 34.57 • Interval -16.9 to 100.0
20.60 Percentage of days
Standard Deviation 32.01 • Interval -30.0 to 100.0
24.13 Percentage of days
Standard Deviation 32.12 • Interval -50.0 to 100.0
20.94 Percentage of days
Standard Deviation 32.97 • Interval -23.6 to 100.0

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean FEV1 during the treatment period (mean value at Week 4)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=93 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=88 Participants
placebo oral tablet, twice daily
Forced Expiratory Volume in 1 Second (FEV1) at the Clinic
2.653 L
Standard Deviation 1.051 • Interval -0.76 to 2.02
2.739 L
Standard Deviation 1.028 • Interval -0.73 to 2.16
2.628 L
Standard Deviation 1.057 • Interval -2.46 to 2.04
2.400 L
Standard Deviation 0.945 • Interval -0.74 to 1.26

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean FVC during the treatment period (mean value at Week 4)

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=93 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=88 Participants
placebo oral tablet, twice daily
Forced Vital Capacity (FVC) at the Clinic
3.704 L
Standard Deviation 1.268 • Interval -1.48 to 2.21
3.892 L
Standard Deviation 1.295 • Interval -0.98 to 2.3
3.546 L
Standard Deviation 1.257 • Interval -1.03 to 2.68
3.563 L
Standard Deviation 1.215 • Interval -0.99 to 2.02

SECONDARY outcome

Timeframe: Week 4

Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean ACQ5 score during the treatment period (mean value at Week 4). Scores range from 0 (good) to 6 (poor control).

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=89 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=86 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=85 Participants
placebo oral tablet, twice daily
Asthma Control Questionnaire 5 Items (ACQ5)
1.69 Scores on a scale
Full Range -2.40 • Interval 0.0 to 4.0
1.58 Scores on a scale
Full Range -2.40 • Interval 0.0 to 3.8
1.64 Scores on a scale
Full Range -3.20 • Interval 0.0 to 4.6
1.91 Scores on a scale
Full Range -2.60 • Interval 0.0 to 4.2

SECONDARY outcome

Timeframe: 4 weeks

Number of patients reporting at least one event

Outcome measures

Outcome measures
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 Participants
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 Participants
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 Participants
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 Participants
placebo oral tablet, twice daily
Adverse Event (AE)
28 Participants
22 Participants
33 Participants
24 Participants

Adverse Events

AZD1981 50 mg Twice Daily (Bid)

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

AZD1981 400 mg Twice Daily (Bid)

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

AZD1981 1000 mg Twice Daily (Bid)

Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 participants at risk
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 participants at risk
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 participants at risk
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 participants at risk
placebo oral tablet, twice daily
Hepatobiliary disorders
Cholelithiasis
0.00%
0/95
0.00%
0/90
1.1%
1/92
0.00%
0/91
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.00%
0/95
0.00%
0/90
0.00%
0/92
1.1%
1/91

Other adverse events

Other adverse events
Measure
AZD1981 50 mg Twice Daily (Bid)
n=95 participants at risk
AZD1981 oral tablet 50 mg, twice daily
AZD1981 400 mg Twice Daily (Bid)
n=90 participants at risk
AZD1981 oral tablet 400 mg, twice daily
AZD1981 1000 mg Twice Daily (Bid)
n=92 participants at risk
AZD1981 oral tablet 1000 mg, twice daily
Placebo
n=91 participants at risk
placebo oral tablet, twice daily
Gastrointestinal disorders
Gastritis
1.1%
1/95
2.2%
2/90
5.4%
5/92
3.3%
3/91
Nervous system disorders
Headache
2.1%
2/95
4.4%
4/90
3.3%
3/92
2.2%
2/91
Respiratory, thoracic and mediastinal disorders
Asthma
2.1%
2/95
1.1%
1/90
3.3%
3/92
4.4%
4/91

Additional Information

Alison Holt

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60