Study to assess the efficacy and safety of AZD1981 in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) - Columbus

Study identifier:D9831C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 4 week double-blind, placebo-controlled, randomized, parallel group phase IIa study to assess the efficacy and safety of AZD1981 in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD)

Medical condition

Moderate to severe COPD

Phase

Phase 2

Healthy volunteers

Study drug

AZD1981, Placebo

Sex

All

Actual Enrollment

118

Study type

Interventional

Age

40 Years +

Date

Study Start Date: 01 May 2008

Primary Completion Date: 01 Dec 2008

Study Completion Date: 01 Dec 2008

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2013 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

PLEVEN, Bulgaria

Location

Research Site

RUSSE, Bulgaria

Location

Research Site

SOFIA, Bulgaria

Location

Research Site

VARNA, Bulgaria

Location

Research Site

ARHUS C, Denmark

Location

Research Site

HELLERUP, Denmark

Location

Research Site

HVIDOVRE, Denmark

Location

Research Site

VAERLOSE, Denmark

Arms	Assigned Interventions
Experimental: AZD1981 AZD1981 Oral tablet, twice daily	Drug: AZD1981 Oral tablet, twice daily
Placebo Comparator: Placebo Placebo Oral tablet, twice daily	Drug: Placebo Placebo Oral tablet, twice daily

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
118 patients were allocated to treatment and 111 completed the study. First patient entered the study on 26 May 2008 and the last patient finished the study on 17 December 2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Participant Flow: Overall Study

	AZD1981	Placebo
STARTED	61	57
COMPLETED	57	54
NOT COMPLETED	4	3
Adverse Event	2	1
Incorrect enrolment	0	1
Study-specific discontinuation criteria	1	0
Intake of prohibited medicine	1	0
withdrew consent at rand.day	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

One patient randomised to placebo withdrew consent immediately after the first dose of investigational product on the day of randomisation. No clinical measurements were performed and no reports of AEs were received for this patient. Since the patient is non-informative both in terms of efficacy and safety, he has been excluded from the analyses.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Baseline Measures

	AZD1981	Placebo	Total
Number of Participants [units: Participants]	61	56	117
Age Continuous [units: Years] Mean ( Full Range )	64.1 (47 to 78)	62.4 (43 to 83)	62.4 (43 to 83)
Gender, Male/Female [units: Participants]
Female	12	8	20
Male	49	48	97

Outcome Measures

1. Primary Outcome Measure: FEV1 [ Time Frame: Baseline and Week 4 ]

Measure Type	Primary
Measure Name	FEV1
Measure Description	Mean change in FEV1 from baseline to Week 4 (last measurement post dose used, if data missing)
Time Frame	Baseline and Week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	60	55
FEV1 [units: L] Mean (Full Range)	0.007 (-0.810 to 0.740)	0.011 (-0.550 to 0.550)

No statistical analysis provided for FEV1

2. Primary Outcome Measure: Clinical COPD Questionnaire [ Time Frame: Baseline and Week 4 ]

Measure Type	Primary
Measure Name	Clinical COPD Questionnaire
Measure Description	Mean change in Total CCQ from baseline to Week 4 (last measurement post dose used, if data missing). Scores for total CCQ range from 0 (low symptoms) to 6 (high symptoms).
Time Frame	Baseline and Week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	59	55
Clinical COPD Questionnaire [units: Scores on a scale] Mean (Full Range)	-0.299 (-2.00 to 1.30)	-0.340 (-2.20 to 1.30)

No statistical analysis provided for Clinical COPD Questionnaire

3. Secondary Outcome Measure: Forced Vital Capacity [ Time Frame: Baseline and Week 4 ]

Measure Type	Secondary
Measure Name	Forced Vital Capacity
Measure Description	Mean change in FVC from baseline to Week 4 (last measurement post dose used, if data missing)
Time Frame	Baseline and Week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	60	55
Forced Vital Capacity [units: L] Mean (Full Range)	-0.047 (-1.74 to 0.840)	-0.102 (-1.09 to 0.870)

No statistical analysis provided for Forced Vital Capacity

4. Secondary Outcome Measure: Slow Vital Capacity [ Time Frame: Baseline and Week 4 ]

Measure Type	Secondary
Measure Name	Slow Vital Capacity
Measure Description	Mean change in SVC from baseline to Week 4 (last measurement post dose used, if data missing)
Time Frame	Baseline and Week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	60	55
Slow Vital Capacity [units: L] Mean (Full Range)	-0.001 (-1.03 to 2.30)	-0.009 (-1.60 to 0.910)

No statistical analysis provided for Slow Vital Capacity

5. Secondary Outcome Measure: Inspiratory Capacity [ Time Frame: Baseline and Week 4 ]

Measure Type	Secondary
Measure Name	Inspiratory Capacity
Measure Description	Mean change in IC from baseline to Week 4 (last measurement post dose used, if data missing)
Time Frame	Baseline and Week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	60	54
Inspiratory Capacity [units: L] Mean (Full Range)	-0.007 (-0.960 to 1.08)	-0.110 (-1.39 to 1.59)

No statistical analysis provided for Inspiratory Capacity

6. Secondary Outcome Measure: FEF25%-75% [ Time Frame: Baseline and Week 4 ]

Measure Type	Secondary
Measure Name	FEF25%-75%
Measure Description	Mean change in FEF25%-75% (forced expiratory flow between 25% and 75% of the FVC) from baseline to Week 4 (last measurement post dose used, if data missing)
Time Frame	Baseline and Week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	60	54
FEF25%-75% [units: L/s] Mean (Full Range)	-0.042 (-0.900 to 0.440)	0.060 (-0.640 to 2.48)

No statistical analysis provided for FEF25%-75%

7. Secondary Outcome Measure: COPD symptom sleep score [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	COPD symptom sleep score
Measure Description	Mean change in COPD symptom sleep score from baseline to treatment period average (calculated using all available data after randomisation for each patient). Scores for COPD symptom sleep score range from 0 (no symptoms) to 4 (no sleep).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	61	56
COPD symptom sleep score [units: Scores on a scale] Mean (Full Range)	-0.147 (-1.55 to 1.00)	-0.047 (-1.75 to 1.80)

No statistical analysis provided for COPD symptom sleep score

8. Secondary Outcome Measure: COPD symptom breathing score [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	COPD symptom breathing score
Measure Description	Mean change in COPD symptom breathing score from baseline to treatment period average (calculated using all available data after randomisation for each patient). Scores for COPD symptom breathing score range from 0 (none) to 4 (severe).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	61	56
COPD symptom breathing score [units: Scores on a scale] Mean (Full Range)	-0.280 (-2.07 to 0.486)	-0.137 (-1.41 to 1.52)

No statistical analysis provided for COPD symptom breathing score

9. Secondary Outcome Measure: COPD symptom cough score [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	COPD symptom cough score
Measure Description	Mean change in COPD symptom cough score from baseline to treatment period average (calculated using all available data after randomisation for each patient). Scores for COPD symptom cough score range from 0 (none) to 4 (almost constant).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	61	56
COPD symptom cough score [units: Scores on a scale] Mean (Full Range)	-0.202 (-2.09 to 1.22)	-0.124 (-1.79 to 1.01)

No statistical analysis provided for COPD symptom cough score

10. Secondary Outcome Measure: COPD symptom sputum score [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	COPD symptom sputum score
Measure Description	Mean change in COPD symptom sputum score from baseline to treatment period average (calculated using all available data after randomisation for each patient). Scores for COPD symptom sputum score range from 0 (none) to 4 (severe).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	61	56
COPD symptom sputum score [units: Scores on a scale] Mean (Full Range)	-0.300 (-1.50 to 0.844)	-0.290 (-1.58 to 0.796)

No statistical analysis provided for COPD symptom sputum score

11. Secondary Outcome Measure: PEF (Peak Expiratory Flow) morning [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	PEF (Peak Expiratory Flow) morning
Measure Description	Mean change in PEF morning from baseline to treatment period average (calculated using all available data after randomisation for each patient).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	61	56
PEF (Peak Expiratory Flow) morning [units: L/min] Mean (Full Range)	2.86 (-45.0 to 113)	4.54 (-37.2 to 77.9)

No statistical analysis provided for PEF (Peak Expiratory Flow) morning

12. Secondary Outcome Measure: PEF (Peak Expiratory Flow) evening [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	PEF (Peak Expiratory Flow) evening
Measure Description	Mean change in PEF evening from baseline to treatment period average (calculated using all available data after randomisation for each patient).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	60	56
PEF (Peak Expiratory Flow) evening [units: L/min] Mean (Full Range)	-1.61 (-66.5 to 115)	5.73 (-35.1 to 61.8)

No statistical analysis provided for PEF (Peak Expiratory Flow) evening

13. Secondary Outcome Measure: Total use of reliever [ Time Frame: Baseline and 4-week treatment period average ]

Measure Type	Secondary
Measure Name	Total use of reliever
Measure Description	Mean change in Total use of reliever from baseline to treatment period average (calculated using all available data after randomisation for each patient).
Time Frame	Baseline and 4-week treatment period average
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	59	55
Total use of reliever [units: Number of inhalations per day] Mean (Full Range)	-0.330 (-7.64 to 3.81)	-0.139 (-3.69 to 9.90)

No statistical analysis provided for Total use of reliever

14. Secondary Outcome Measure: Adverse event [ Time Frame: Up to 4 Weeks ]

Measure Type	Secondary
Measure Name	Adverse event
Measure Description	The number of participants that experienced at least one adverse event.
Time Frame	Up to 4 Weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Measured Values

	AZD1981	Placebo
Number of Participants Analyzed [units:participants]	61	56
Adverse event [units: Participants]	20	18

No statistical analysis provided for Adverse event

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Serious Adverse Events

AZD1981

Placebo

Total, serious adverse events

# participants affected / at risk

0/61 (0.00%)

1/56 (1.79%)

Respiratory, thoracic and mediastinal disorders

Chronic Obstructive Pulmonary Disease¹

# participants affected / at risk

0/61 (0.00%)

1/56 (1.79%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD1981	AZD1981 Oral tablet, twice daily
Placebo	Placebo Oral tablet, twice daily

Other Adverse Events

AZD1981

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

8/61 (13.11%)

6/56 (10.71%)

Infections and infestations

NASOPHARYNGITIS¹

# participants affected / at risk

6/61 (9.84%)

3/56 (5.36%)

Respiratory, thoracic and mediastinal disorders

CHRONIC OBSTRUCTIVE PULMONARY DISEASE²

# participants affected / at risk

4/61 (6.56%)

3/56 (5.36%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary, MedDRA 11.1
3	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Alison Holt
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=215&filename=CSR-D9831C00001.pdf
Download
CSR-D9831C00001.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

Eva Pettersson

+46 46 336140

Eva.S.Pettersson@astrazeneca.com

Investigators

Principal Investigator

Jörgen Vestbo

Professor in Respiratory Medicine, Hvidovre, Denmark

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=215&filename=CSR-D9831C00001.pdf

CSR-D9831C00001.pdf

Trial Results Summaries