Investigation of Efficacy, Safety and Tolerability of Once and Twice Daily Doses of AZD1981 in Asthmatic Patients

A Double-blind, Placebo-controlled, Randomised, Parallel-group, Phase II, Multi-centre Study to Assess the Efficacy, Safety and Tolerability of 4 Twice Daily Doses and 2 Once Daily Doses of AZD1981 Given as Tablets During 12 Weeks in Asthmatic Patients

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01197794

Acronym

Sweapea

Enrollment

1144

Registered

2010-09-09

Start date

2010-10-31

Completion date

2012-02-29

Last updated

2013-11-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma Patients

Keywords

Efficacy, safety, tolerability, dose finding, asthma patients

Brief summary

The study will assess the efficacy, safety and tolerability of AZD1981 compared to non-active compound in asthmatic patients.

Interventions

DRUGAZD1981

AZD1981 twice daily

DRUGPlacebo

Placebo to match AZD1981

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Men and women. Women must be surgically sterilized/postmenopausal or use double barrier method contraception * 6 months history of asthma according to ATS definition * Prescribed daily dose of ICS and LABA for at least 3 months prior to Visit 2 * Pre-bronchodilator FEV1 of 40 to 85 % of predicted normal * A total ACQ5 score of 1.5 or more

Exclusion criteria

* Respiratory infection significantly affecting the asthma * Any significant disease and disorder that may put the patient at risk or influence study results * Any clinically relevant abnormal findings * A smoking history of more than 10 pack years * Intake of oral, rectal or parenteral glucocorticosteroids

Design outcomes

Primary

Measure	Time frame	Description
Pre-bronchodilator FEV1 at the Clinic	Twelve week treatment period	Change from baseline: treatment period average minus baseline. Treatment period average defined as the mean of all available data during randomized treatment that occurred on or prior to treatment failure. Treatment failure defined as worsening asthma symptoms resulting in increased dose of inhaled corticosteroid.

Secondary

Measure	Time frame	Description
Asthma Control Questionnaire 5-item (ACQ5)	Twelve week treatment period	The ACQ5 consists of 5 questions, each assessed on a scale from 0-6, where 0 represents good asthma control and 6 represents poor asthma control. The overall score is the mean of the responses. The minimal important difference is defined as a change in score of 0.5. Change from baseline: treatment period average minus baseline.
Adverse Events	Twelve week treatment period	Number of participants who had at least one adverse event during the randomized treatment period
Number of Participants With at Least One Severe Asthma Exacerbation	Twelve week treatment period	Severe asthma exacerbation defined as deterioration in asthma leading to either hospitalization/emergency room treatment or oral glucocorticosteroid treatment for at least 3 days
Number of Participants With at Least One Treatment Failure	Twelve week treatment period	Treatment failure is defined as a clinical need for additional inhaled corticosteroid use as judged by the investigator based on evaluations at the clinic.
Morning and Evening PEF	Twelve week treatment period	Change from baseline: treatment period average minus baseline. Treatment period average defined as the mean of all available morning (evening) PEF during randomized treatment that occurred on or prior to treatment failure. Treatment failure defined as worsening asthma symptoms resulting in increased dose of inhaled corticosteroid.
Asthma Quality of Life Questionnaire (AQLQ(S))	Twelve week treatment period	The AQLQ(S) consists of 32 questions, each assessed on a scale from 1-7, with higher values indicating better health-related quality of life. Overall scores are calculated from the means of the individual scores. The minimal important difference is a change in score of 0.5. Change from baseline: treatment period average minus baseline.
Asthma Symptom Score	Twelve week treatment period	Asthma symptoms, measured in the morning and evening, based on a scale from 0-3 with higher scores indicating more severe asthma symptoms. Total asthma symptom score (0-6) is calculated by taking the sum of the morning and evening scores. Change from baseline: treatment period average minus baseline.
Total Reliever Medication Use	Twelve week treatment period	Reliever medication use (number of inhalations), measured in the morning and evening. Total reliever medication use is calculated by taking the sum of the number of daytime and evening inhalations of reliever medication. Change from baseline: treatment period average minus baseline.
Number of Participants With Well-controlled Asthma (ACQ5<=0.75)	Twelve week treatment period	The ACQ5 consists of 5 questions, each assessed on a scale from 0-6, where 0 represents good asthma control and 6 represents poor asthma control. The overall score is the mean of the responses. Well-controlled asthma is defined as ACQ5\<=0.75 at the end of the 12-week treatment period.

Countries

Argentina, Brazil, Japan, Mexico, Romania, Russia, Slovakia, South Africa, Ukraine, United States

Participant flow

Recruitment details

1144 participants were randomized. The first participant was enrolled on 19 October 2010 and the last participant completed the study on 16 February 2012.

Pre-assignment details

Participants were screened for a period of 31 days out of which 17 days for enrollment and 2 weeks for run-in period.

Participants by arm

Arm	Count
AZD1981 400 mg AZD1981 400 mg twice daily	164
AZD1981 200 mg AZD1981 200 mg once daily	161
AZD1981 100 mg AZD1981 100 mg twice daily	166
AZD1981 80 mg AZD1981 80 mg once daily	164
AZD1981 40 mg AZD1981 40 mg twice daily	162
AZD1981 10 mg AZD1981 10 mg twice daily	163
Placebo Placebo	161
Total	1,141

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006
Overall Study	Adverse Event	3	2	4	4	4	2	3
Overall Study	Development of study withdrawal criteria	3	0	0	1	0	0	1
Overall Study	Eligibility criteria not fulfilled	5	8	2	5	5	9	6
Overall Study	Lost to Follow-up	1	1	0	1	0	1	0
Overall Study	Other	1	1	3	0	2	2	4
Overall Study	Protocol Violation	0	0	0	0	2	0	1
Overall Study	Withdrawal by Subject	3	3	4	1	1	5	6

Baseline characteristics

Characteristic	Total	Placebo	AZD1981 10 mg	AZD1981 400 mg	AZD1981 40 mg	AZD1981 80 mg	AZD1981 100 mg	AZD1981 200 mg
Age Continuous	45.9 Years STANDARD_DEVIATION 13.58	45.7 Years STANDARD_DEVIATION 13.5	44.5 Years STANDARD_DEVIATION 13.76	46.6 Years STANDARD_DEVIATION 13.98	46.3 Years STANDARD_DEVIATION 13.15	45.4 Years STANDARD_DEVIATION 13.22	46.4 Years STANDARD_DEVIATION 14.65	46.7 Years STANDARD_DEVIATION 12.84
Pre-bronchodilator FEV1 percentage of predicted normal (PN) at randomization	68.73 Percentage of predicted normal STANDARD_DEVIATION 11.615	68.52 Percentage of predicted normal STANDARD_DEVIATION 11.319	69.06 Percentage of predicted normal STANDARD_DEVIATION 12.132	70.03 Percentage of predicted normal STANDARD_DEVIATION 10.544	67.28 Percentage of predicted normal STANDARD_DEVIATION 11.732	68.56 Percentage of predicted normal STANDARD_DEVIATION 12.186	68.86 Percentage of predicted normal STANDARD_DEVIATION 11.774	68.86 Percentage of predicted normal STANDARD_DEVIATION 11.58
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	195 Participants	24 Participants	32 Participants	27 Participants	25 Participants	32 Participants	29 Participants	26 Participants
Race/Ethnicity, Customized Black or African American	26 Participants	4 Participants	3 Participants	5 Participants	1 Participants	2 Participants	5 Participants	6 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	94 Participants	14 Participants	15 Participants	14 Participants	14 Participants	11 Participants	12 Participants	14 Participants
Race/Ethnicity, Customized White	824 Participants	119 Participants	113 Participants	117 Participants	121 Participants	119 Participants	120 Participants	115 Participants
Sex: Female, Male Female	561 Participants	76 Participants	80 Participants	76 Participants	82 Participants	78 Participants	87 Participants	82 Participants
Sex: Female, Male Male	580 Participants	85 Participants	83 Participants	88 Participants	80 Participants	86 Participants	79 Participants	79 Participants
Smoking status Former smoker	144 Participants	15 Participants	19 Participants	25 Participants	26 Participants	21 Participants	14 Participants	24 Participants
Smoking status Never	997 Participants	146 Participants	144 Participants	139 Participants	136 Participants	143 Participants	152 Participants	137 Participants
Time since asthma diagnosis	18.1 Years STANDARD_DEVIATION 13.7	17.5 Years STANDARD_DEVIATION 13.27	17.3 Years STANDARD_DEVIATION 12.4	18.6 Years STANDARD_DEVIATION 13.87	18.0 Years STANDARD_DEVIATION 14.35	18.3 Years STANDARD_DEVIATION 13.04	18.6 Years STANDARD_DEVIATION 14.74	18.5 Years STANDARD_DEVIATION 14.25
Total daily dose of inhaled glucocorticosteroids (ICS)	407.30 µg	410.99 µg	418.19 µg	406.31 µg	405.56 µg	396.46 µg	413.70 µg	399.75 µg

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	12 / 164	23 / 159	22 / 164	21 / 164	20 / 163	32 / 163	21 / 163
serious Total, serious adverse events	0 / 164	1 / 159	3 / 164	1 / 164	0 / 163	0 / 163	1 / 163

Outcome results

Primary

Pre-bronchodilator FEV1 at the Clinic

Change from baseline: treatment period average minus baseline. Treatment period average defined as the mean of all available data during randomized treatment that occurred on or prior to treatment failure. Treatment failure defined as worsening asthma symptoms resulting in increased dose of inhaled corticosteroid.