Trial Outcomes & Findings for A Phase IIa Study Assessing the Effects of AZD1236 on Biomarkers in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT00758706)

NCT ID: NCT00758706

Last Updated: 2015-04-16

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 55 participants
• Primary outcome timeframe: Baseline and Week 6
• Results posted on: 2015-04-16

Participant Flow

Participant milestones

Measure	AZD1236 AZD1236 75mg oral tablet twice daily(bid)	Placebo Placebo to AZD1236 twice daily(bid)
Overall Study STARTED	26	29
Overall Study COMPLETED	22	25
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Measure	AZD1236 AZD1236 75mg oral tablet twice daily(bid)	Placebo Placebo to AZD1236 twice daily(bid)
Overall Study Adverse Event	4	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)	Total n=55 Participants Total of all reporting groups
Age, Continuous	62.9 Year n=5 Participants	65.7 Year n=7 Participants	64.1 Year n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

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

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).

Outcome measures

Measure	AZD1236 n=23 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=27 Participants Placebo to AZD1236 twice daily(bid)
Ratio of TNF Alpha at Week 6 to Baseline	1.37 ratio Full Range 0.532 • Interval 0.532 to 18.7	1.21 ratio Full Range 0.270 • Interval 0.27 to 20.4

PRIMARY outcome

Timeframe: Baseline and Week 6

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

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).

Outcome measures

Measure	AZD1236 n=23 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=27 Participants Placebo to AZD1236 twice daily(bid)
Ratio of Sputum Total Cells at Week 6 to Baseline	1.07 ratio Full Range 0.209 • Interval 0.209 to 4.03	0.876 ratio Full Range 0.002 • Interval 0.002 to 13.5

PRIMARY outcome

Timeframe: Baseline and Week 6

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

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

Outcome measures

Measure	AZD1236 n=24 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=28 Participants Placebo to AZD1236 twice daily(bid)
Ratio of Total Urine Desmosine at Week 6 to Baseline	0.946 ratio Full Range 0.240 • Interval 0.24 to 5.44	1.27 ratio Full Range 0.387 • Interval 0.387 to 5.73

SECONDARY outcome

Timeframe: all study visits

Number of patients who had an AE

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Incidence of Adverse Events	15 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set completed at week 6

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

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=28 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6	-0.025 L Full Range -0.510 • Interval -0.51 to 0.67	-0.063 L Full Range -0.670 • Interval -0.67 to 0.55

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set completed at week 6

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

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=28 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Forced Vital Capacity (FVC) at Week 6	-0.103 L Full Range -0.960 • Interval -0.96 to 0.74	-0.104 L Full Range -0.900 • Interval -0.9 to 1.23

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set completed at week 6

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

Outcome measures

Measure	AZD1236 n=25 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=28 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Vital Capacity (VC) at Week 6	0.098 L Full Range -0.680 • Interval -0.68 to 2.72	-0.110 L Full Range -0.840 • Interval -0.84 to 0.59

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set completed at week 6

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

Outcome measures

Measure	AZD1236 n=25 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=28 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Inspiratory Capacity (IC) at Week 6	-0.082 L Full Range -0.700 • Interval -0.7 to 0.5	-0.173 L Full Range -2.19 • Interval -2.19 to 0.84

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set completed at week 6

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

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=28 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6	-0.007 L/s Full Range -0.410 • Interval -0.41 to 0.26	-0.067 L/s Full Range -0.780 • Interval -0.78 to 0.23

SECONDARY outcome

Timeframe: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Population: Full analysis set

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.

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment	-9.81 L/min Full Range -61.2 • Interval -61.2 to 26.2	-7.73 L/min Full Range -73.2 • Interval -73.2 to 43.4

SECONDARY outcome

Timeframe: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Population: Full analysis set

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.

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment	-13.6 L/min Full Range -80.3 • Interval -80.3 to 30.1	-13.5 L/min Full Range -102 • Interval -102.0 to 27.4

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set

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)

Outcome measures

Measure	AZD1236 n=25 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=27 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in Clinical COPD Questionnaire(CCQ) Total	0.011 Score on scale Full Range -0.800 • Interval -0.8 to 1.4	-0.241 Score on scale Full Range -1.74 • Interval -1.74 to 1.2

SECONDARY outcome

Timeframe: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Population: Full analysis set

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).

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment	-0.191 Score on scale Full Range -1.51 • Interval -1.51 to 1.0	-0.338 Score on scale Full Range -1.74 • Interval -1.74 to 1.42

SECONDARY outcome

Timeframe: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Population: Full analysis set

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).

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment	-0.149 Score on scale Full Range -1.11 • Interval -1.11 to 1.0	-0.156 Score on scale Full Range -1.74 • Interval -1.74 to 1.27

SECONDARY outcome

Timeframe: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Population: Full analysis set

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).

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment	-0.114 Score on scale Full Range -1.81 • Interval -1.81 to 1.78	-0.324 Score on scale Full Range -1.94 • Interval -1.94 to 1.13

SECONDARY outcome

Timeframe: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)

Population: Full analysis set

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).

Outcome measures

Measure	AZD1236 n=26 Participants AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 Participants Placebo to AZD1236 twice daily(bid)
Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment	0.072 Score on scale Full Range -0.556 • Interval -0.556 to 1.38	-0.150 Score on scale Full Range -2.22 • Interval -2.22 to 0.976

Adverse Events

AZD1236

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD1236 n=26 participants at risk AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 participants at risk Placebo to AZD1236 twice daily(bid)
Respiratory, thoracic and mediastinal disorders Exacerbation COPD	7.7% 2/26	0.00% 0/29
Respiratory, thoracic and mediastinal disorders Increased Dyspnoe After Stopping Normal Treatment	3.8% 1/26	0.00% 0/29
Cardiac disorders Decompensation Cordis	3.8% 1/26	0.00% 0/29

Other adverse events

Measure	AZD1236 n=26 participants at risk AZD1236 75mg oral tablet twice daily(bid)	Placebo n=29 participants at risk Placebo to AZD1236 twice daily(bid)
Respiratory, thoracic and mediastinal disorders COPD	11.5% 3/26	10.3% 3/29
Infections and infestations influenza	3.8% 1/26	10.3% 3/29
Infections and infestations nasopharyngitis	3.8% 1/26	10.3% 3/29
General disorders oedema peripheral	7.7% 2/26	3.4% 1/29

Additional Information

Gerard Lynch

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

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

Restriction type: LTE60