BICO: A Phase IIa Study Assessing the Effects of AZD1236 on Biomarkers in Chronic Obstructive Pulmonary Disease (COPD) Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00758706
• Collaborator: (none)
• Enrollment: 55
• Locations: 10
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The primary aim of this study is to investigate the effects of AZD1236 compared with placebo ("inactive substance") in COPD patients by analysing biomarkers for inflammation and tissue degradation in blood, urine and sputum.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: AZD1236; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomised, Placebo-controlled, Parallel Group Multi-centre Phase IIa Study to Assess the Effects on Biomarkers in Induced Sputum, Bood and Uine of AZD1236 Administered as Oral Tablet in Moderate to Severe COPD Patients During a 6 Week Period.
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD1236 oral tablet, 75 mg, twice daily during 6 weeks	Drug: AZD1236; oral tablet, 75 mg, twice daily during 6 weeks
Placebo Comparator: Placebo Dosing to match AZD1236	Drug: Placebo; Dosing to match AZD1236

Outcome Measures

Primary Outcome Measures

1. Ratio of TNF Alpha at Week 6 to Baseline [Baseline and Week 6]

   Ratio reflects Sputum Tumor Necrosis Factor alpha (TNF alpha) at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization).

2. Ratio of Sputum Total Cells at Week 6 to Baseline [Baseline and Week 6]

   Ratio reflects Sputum Total Cells at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization).

3. Ratio of Total Urine Desmosine at Week 6 to Baseline [Baseline and Week 6]

   Ratio reflects Total Urine Desmosine at week 6 value divide by baseline value. Baseline is visit 3(Randomization) value.

Secondary Outcome Measures

1. Incidence of Adverse Events [all study visits]

   Number of patients who had an AE

2. Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6 [Baseline and Week 6]

   Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.

3. Change From Baseline in Forced Vital Capacity (FVC) at Week 6 [Baseline and Week 6]

   Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.

4. Change From Baseline in Vital Capacity (VC) at Week 6 [Baseline and Week 6]

   Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.

5. Change From Baseline in Inspiratory Capacity (IC) at Week 6 [Baseline and Week 6]

   Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.

6. Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6 [Baseline and Week 6]

   Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.

7. Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment [Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)]

   Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in.

8. Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment [Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)]

   Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in.

9. Change From Baseline in Clinical COPD Questionnaire(CCQ) Total [Baseline and Week 6]

   Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited)

10. Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment [Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)]

    Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe).

11. Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment [Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)]

    Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe).

12. Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment [Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)]

    Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant).

13. Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment [Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)]

    Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of COPD for 1 month

• Men or postmenopausal women

• Spirometry values indicating symptomatic patients

• Smoking history equivalent to using 20 cigarettes a day for 10 years.

Exclusion Criteria:

• Any current respiratory tract disorders other than COPD

• Requirement for regular oxygen therapy

• Acute worsening of COPD (exacerbation) 1,5 month prior to study drug administration

• Use of oral or parenteral glucocorticosteroids within 30 days and use of inhaled steroids 14 days prior to the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Alborg		Denmark
2	Research Site	Arhus C		Denmark
3	Research Site	Kobenhavn Nv		Denmark
4	Research Site	Odense C		Denmark
5	Research Site	Helsinki		Finland
6	Research Site	Tampere		Finland
7	Research Site	Eindhoven		Netherlands
8	Research Site	Nieuwegein		Netherlands
9	Research Site	Oslo		Norway
10	Research Site	Trondheim		Norway

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Ronald Dahl, MD, Professor, Arhus Kommune HospitalMedicinsk
• Study Director: Andrew Lockton, MD, AstraZeneca R&D Charnwood

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• D4260C00007

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00758706
• Other Study ID Numbers: D4260C00007
• First Posted: Sep 25, 2008
• Last Update Posted: Apr 16, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by AstraZeneca: COPD
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Period Title: Overall Study
STARTED	26	29
COMPLETED	22	25
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	AZD1236	Placebo	Total
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)	Total of all reporting groups
Overall Participants	26	29	55
Age (Year) [Mean (Full Range) ]
Mean (Full Range) [Year]	62.9	65.7	64.1
Sex: Female, Male (Count of Participants)
Female	7 26.9%	9 31%	16 29.1%
Male	19 73.1%	20 69%	39 70.9%

Outcome Measures

1. Primary Outcome

Title	Ratio of TNF Alpha at Week 6 to Baseline
Description	Ratio reflects Sputum Tumor Necrosis Factor alpha (TNF alpha) at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization).
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set excluded participants without baseline or post-baseline data.

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	23	27
Mean (Full Range) [ratio]	1.37 (0.532)	1.21 (0.270)

2. Primary Outcome

Title	Ratio of Sputum Total Cells at Week 6 to Baseline
Description	Ratio reflects Sputum Total Cells at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization).
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set excluded participants without baseline or post-baseline data.

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	23	27
Mean (Full Range) [ratio]	1.07 (0.209)	0.876 (0.002)

3. Primary Outcome

Title	Ratio of Total Urine Desmosine at Week 6 to Baseline
Description	Ratio reflects Total Urine Desmosine at week 6 value divide by baseline value. Baseline is visit 3(Randomization) value.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set excluded participants without baseline or post-baseline data.

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	24	28
Mean (Full Range) [ratio]	0.946 (0.240)	1.27 (0.387)

4. Secondary Outcome

Title	Incidence of Adverse Events
Description	Number of patients who had an AE
Time Frame	all study visits

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Number [Participants]	15 57.7%	15 51.7%

5. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6
Description	Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set completed at week 6

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	28
Mean (Full Range) [L]	-0.025 (-0.510)	-0.063 (-0.670)

6. Secondary Outcome

Title	Change From Baseline in Forced Vital Capacity (FVC) at Week 6
Description	Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set completed at week 6

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	28
Mean (Full Range) [L]	-0.103 (-0.960)	-0.104 (-0.900)

7. Secondary Outcome

Title	Change From Baseline in Vital Capacity (VC) at Week 6
Description	Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set completed at week 6

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	25	28
Mean (Full Range) [L]	0.098 (-0.680)	-0.110 (-0.840)

8. Secondary Outcome

Title	Change From Baseline in Inspiratory Capacity (IC) at Week 6
Description	Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set completed at week 6

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	25	28
Mean (Full Range) [L]	-0.082 (-0.700)	-0.173 (-2.19)

9. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6
Description	Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set completed at week 6

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	28
Mean (Full Range) [L/s]	-0.007 (-0.410)	-0.067 (-0.780)

10. Secondary Outcome

Title	Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment
Description	Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in.
Time Frame	Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Mean (Full Range) [L/min]	-9.81 (-61.2)	-7.73 (-73.2)

11. Secondary Outcome

Title	Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment
Description	Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in.
Time Frame	Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Mean (Full Range) [L/min]	-13.6 (-80.3)	-13.5 (-102)

12. Secondary Outcome

Title	Change From Baseline in Clinical COPD Questionnaire(CCQ) Total
Description	Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited)
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	25	27
Mean (Full Range) [Score on scale]	0.011 (-0.800)	-0.241 (-1.74)

13. Secondary Outcome

Title	Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment
Description	Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe).
Time Frame	Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Mean (Full Range) [Score on scale]	-0.191 (-1.51)	-0.338 (-1.74)

14. Secondary Outcome

Title	Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment
Description	Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe).
Time Frame	Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Mean (Full Range) [Score on scale]	-0.149 (-1.11)	-0.156 (-1.74)

15. Secondary Outcome

Title	Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment
Description	Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant).
Time Frame	Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Mean (Full Range) [Score on scale]	-0.114 (-1.81)	-0.324 (-1.94)

16. Secondary Outcome

Title	Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment
Description	Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant).
Time Frame	Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AZD1236	Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)	Placebo to AZD1236 twice daily(bid)
Measure Participants	26	29
Mean (Full Range) [Score on scale]	0.072 (-0.556)	-0.150 (-2.22)

Adverse Events

Arm/Group Title	AZD1236		Placebo
Arm/Group Description	AZD1236 75mg oral tablet twice daily(bid)		Placebo to AZD1236 twice daily(bid)
All Cause Mortality
	AZD1236		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD1236		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/26 (15.4%)		0/29 (0%)
Cardiac disorders
Decompensation Cordis	1/26 (3.8%)		0/29 (0%)
Respiratory, thoracic and mediastinal disorders
Exacerbation COPD	2/26 (7.7%)		0/29 (0%)
Increased Dyspnoe After Stopping Normal Treatment	1/26 (3.8%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	AZD1236		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/26 (26.9%)		10/29 (34.5%)
General disorders
oedema peripheral	2/26 (7.7%)		1/29 (3.4%)
Infections and infestations
influenza	1/26 (3.8%)		3/29 (10.3%)
nasopharyngitis	1/26 (3.8%)		3/29 (10.3%)
Respiratory, thoracic and mediastinal disorders
COPD	3/26 (11.5%)		3/29 (10.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.