Trial Outcomes & Findings for A 4 Week Study to Investigate the Safety and Tolerability of AZD5069 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01233232)

NCT ID: NCT01233232

Last Updated: 2015-09-17

Results Overview

Adverse event (AE) data, both serious and non-serious. An AE is the development of an undesirable medical condition (eg, nausea, chest pain, tachycardia, laboratory findings) or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 109 participants
• Primary outcome timeframe: From start of treatment (Day 0) up to 28 days (End of Treatment)
• Results posted on: 2015-09-17

Participant Flow

First patient enrolled: 22 November 2010. Last patient completed: 22 March 2011. Fifteen centres across 4 countries participated in this study: Bulgaria (4), Germany (4), Hungary (4) and Ukraine (3)

22 patients enrolled were not randomized due to eligibility not fulfilled (17 patients) and voluntary discontinuation (5 patients)

Participant milestones

Measure	Placebo 4 x placebo capsules, twice daily (bid)	AZD5069 50 mg 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	AZD5069 80 mg 4 x 20 AZD5069 mg capsules, bid
Overall Study STARTED	29	30	28
Overall Study COMPLETED	28	30	28
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Measure	Placebo 4 x placebo capsules, twice daily (bid)	AZD5069 50 mg 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	AZD5069 80 mg 4 x 20 AZD5069 mg capsules, bid
Overall Study Voluntary Discontinuation by Subject	1	0	0

Baseline Characteristics

A 4 Week Study to Investigate the Safety and Tolerability of AZD5069 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	Placebo n=29 Participants 4 x placebo capsules, twice daily (bid)	AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid	Total n=87 Participants Total of all reporting groups
Age, Continuous	62 Years STANDARD_DEVIATION 7.9 • n=5 Participants	65 Years STANDARD_DEVIATION 6.9 • n=7 Participants	65 Years STANDARD_DEVIATION 7.4 • n=5 Participants	64 Years STANDARD_DEVIATION 7.4 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	12 Participants n=7 Participants	6 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	18 Participants n=7 Participants	22 Participants n=5 Participants	60 Participants n=4 Participants
Body Mass Index	24.842 kg/m^2 STANDARD_DEVIATION 2.77 • n=5 Participants	27.645 kg/m^2 STANDARD_DEVIATION 2.89 • n=7 Participants	25.803 kg/m^2 STANDARD_DEVIATION 3.18 • n=5 Participants	26.118 kg/m^2 STANDARD_DEVIATION 3.14 • n=4 Participants
Weight	73.7 Kg STANDARD_DEVIATION 14.02 • n=5 Participants	78.9 Kg STANDARD_DEVIATION 9.18 • n=7 Participants	75.4 Kg STANDARD_DEVIATION 10.90 • n=5 Participants	76 Kg STANDARD_DEVIATION 11.59 • n=4 Participants
% Predicted FEV1 at screening	56 % STANDARD_DEVIATION 13.9 • n=5 Participants	57 % STANDARD_DEVIATION 13.6 • n=7 Participants	54 % STANDARD_DEVIATION 12.1 • n=5 Participants	56 % STANDARD_DEVIATION 13.2 • n=4 Participants
FEV1/FVC at screening	52.54 % STANDARD_DEVIATION 9.62 • n=5 Participants	51.75 % STANDARD_DEVIATION 11.65 • n=7 Participants	54.52 % STANDARD_DEVIATION 10.51 • n=5 Participants	52.91 % STANDARD_DEVIATION 10.58 • n=4 Participants
Nicotine pack years	38 Pack Year STANDARD_DEVIATION 21.4 • n=5 Participants	39 Pack Year STANDARD_DEVIATION 22 • n=7 Participants	34 Pack Year STANDARD_DEVIATION 17.9 • n=5 Participants	37 Pack Year STANDARD_DEVIATION 20.4 • n=4 Participants
GOLD classification II Moderate	17 Participants n=5 Participants	20 Participants n=7 Participants	16 Participants n=5 Participants	53 Participants n=4 Participants
GOLD classification III Severe	12 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants

PRIMARY outcome

Timeframe: From start of treatment (Day 0) up to 28 days (End of Treatment)

Adverse event (AE) data, both serious and non-serious. An AE is the development of an undesirable medical condition (eg, nausea, chest pain, tachycardia, laboratory findings) or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Outcome measures

Measure	Arm 1 - Placebo n=29 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Patients Who Experienced at Least One Adverse Events(s)	9 Participants	10 Participants	6 Participants

PRIMARY outcome

Timeframe: Last Observation on Treatment (up to Day 28)

Physical examination includes assessment of general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, musculo-skeletal (including spine and extremities), cardiovascular, lungs and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator.

Outcome measures

Measure	Arm 1 - Placebo n=29 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Number of Participants With Abnormal Physical Examination Findings	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

ECGs were recorded in the supine position after the patient has rested for 10 minutes. Heart rate, QRS duration, PR, RR and QT intervals were recorded. Overall evaluation of the ECG is classified as normal, abnormal or borderline. Only participants with ECG at baseline classified as normal are reported (ie, only changes from normal to abnormal).

Outcome measures

Measure	Arm 1 - Placebo n=22 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=25 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=23 Participants 4 x 20 AZD5069 mg capsules, bid
Number of Participants With Abnormal Electrocardiogram (ECG)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in circulating leucocyte counts (including neutrophils) is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=28 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=28 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)	-0.12 10^9/L cells/L Standard Deviation 1.974	-1.55 10^9/L cells/L Standard Deviation 2.059	-1.08 10^9/L cells/L Standard Deviation 2.404

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in body temperature (oral) is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=28 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for Body Temperature	-0.1 degrees C Standard Deviation 0.43	0.0 degrees C Standard Deviation 0.57	-0.0 degrees C Standard Deviation 0.39

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in systolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=28 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs)	3.0 mmHg Standard Deviation 11.0	-0.0 mmHg Standard Deviation 12.1	-3.0 mmHg Standard Deviation 15.7

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in diastolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=28 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs)	2.0 mmHg Standard Deviation 7.2	-2.0 mmHg Standard Deviation 7.9	-1.0 mmHg Standard Deviation 8.2

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in pulse rate (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=28 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for Pulse Rate (Vital Signs)	1 beats/minute Standard Deviation 6.2	-1 beats/minute Standard Deviation 6.9	3 beats/minute Standard Deviation 7.9

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in FEV1 Pre-bronchodilator is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=28 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=27 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test)	-0.03 L Standard Deviation 0.238	0.05 L Standard Deviation 0.238	-0.01 L Standard Deviation 0.218

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in FEV1 Post-bronchodilator is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=27 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test)	-0.02 L Standard Deviation 0.230	0.10 L Standard Deviation 0.256	0.02 L Standard Deviation 0.194

PRIMARY outcome

Timeframe: Up to Follow-up Visit (3 to 18 days after End of Treatment [Day 28])

High Transaminase Values are defined as a measurment of ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than or equal to 3 times the upper limit of normal (ALT ULN = 36 IU/L, AST ULN = 33 IU/L).

Outcome measures

Measure	Arm 1 - Placebo n=29 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=28 Participants 4 x 20 AZD5069 mg capsules, bid
Number of Participants Who Developed High Transaminase Values (Clinical Chemistry)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in total protein in urine is calculated as the End of Treatment value minus the Baseline value.

Outcome measures

Measure	Arm 1 - Placebo n=6 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=4 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=1 Participants 4 x 20 AZD5069 mg capsules, bid
Change From Baseline to End of Treatment for Total Protein (Urinalysis)	-0.02 g/L Standard Deviation 0.034	-0.01 g/L Standard Deviation 0.022	-0.01 g/L Standard Deviation NA Only one value in arm 3. SD is not calculable.

SECONDARY outcome

Timeframe: End of Treatment (Day 28), 1 hour after dosing

At this visit, approximately 1 hour after dosing (at the clinic), a blood sample was collected for determination of drug concentration in plasma.

Outcome measures

Measure	Arm 1 - Placebo 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=18 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=18 Participants 4 x 20 AZD5069 mg capsules, bid
Plasma Concentration of AZD5069 After 1 Hour of Dosing	—	2599.551 nmol/L Standard Deviation 2085.601	5433.611 nmol/L Standard Deviation 4622.932

SECONDARY outcome

Timeframe: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing

The area under the plasma concentration curve is estimated from time 0 (dosing) to 24 hours after dosing.

Outcome measures

Measure	Arm 1 - Placebo n=26 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=22 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg 4 x 20 AZD5069 mg capsules, bid
Area Under the Plasma Concentration Curve of AZD5069	29600 nmol*h/L Geometric Coefficient of Variation 108 • Interval 4270.0 to 136000.0	38800 nmol*h/L Geometric Coefficient of Variation 95.6 • Interval 6700.0 to 143000.0	—

SECONDARY outcome

Timeframe: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing

The maximum plasma concentration (Cmax) is the highest level of drug in plasma.

Outcome measures

Measure	Arm 1 - Placebo n=26 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=22 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg 4 x 20 AZD5069 mg capsules, bid
Maximum Plasma Concentration for AZD5069	2550 nmol/L Geometric Coefficient of Variation 107 • Interval 367.0 to 11700.0	3340 nmol/L Geometric Coefficient of Variation 95.6 • Interval 576.0 to 12300.0	—

SECONDARY outcome

Timeframe: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing

Time (in relation to dosing) at which the maximum plasma concentration is observed.

Outcome measures

Measure	Arm 1 - Placebo n=26 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=22 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg 4 x 20 AZD5069 mg capsules, bid
Time to Maximum Plasma Concentration for AZD5069	1.56 hours Interval 1.56 to 1.56	1.56 hours Interval 1.56 to 1.56	—

SECONDARY outcome

Timeframe: Baseline (last non-missing assessment prior to first dose of study medication), weeks 1, 2 and 3, and End of Treatment (Day 28)

The change in circulating neutrophils in blood is calculated as the visit value minus the Baseline value. Only participants with reduction are considered.

Outcome measures

Measure	Arm 1 - Placebo n=22 Participants 4 x placebo capsules, twice daily (bid)	Arm 2 - AZD5069 50 mg n=30 Participants 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	Arm 3 - AZD5069 80 mg n=26 Participants 4 x 20 AZD5069 mg capsules, bid
Maximum Reduction of Circulating Neutrophils in Blood, From Baseline	1.324 10^9/L cells/L Standard Deviation 1.2152	2.759 10^9/L cells/L Standard Deviation 1.4422	2.678 10^9/L cells/L Standard Deviation 2.0710

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

AZD5069 50 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

AZD5069 80 mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=29 participants at risk 4 x placebo capsules, twice daily (bid)	AZD5069 50 mg n=30 participants at risk 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	AZD5069 80 mg n=28 participants at risk 4 x 20 AZD5069 mg capsules, bid
Cardiac disorders Atrial Fibrillation	0.00% 0/29	3.3% 1/30	0.00% 0/28
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/29	0.00% 0/30	3.6% 1/28

Other adverse events

Measure	Placebo n=29 participants at risk 4 x placebo capsules, twice daily (bid)	AZD5069 50 mg n=30 participants at risk 1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid	AZD5069 80 mg n=28 participants at risk 4 x 20 AZD5069 mg capsules, bid
Infections and infestations Nasopharyngitis	6.9% 2/29	13.3% 4/30	0.00% 0/28
Gastrointestinal disorders Diarrhoea	3.4% 1/29	6.7% 2/30	0.00% 0/28
General disorders Pyrexia	6.9% 2/29	3.3% 1/30	0.00% 0/28
Investigations Neutrophil Count Decreased	0.00% 0/29	10.0% 3/30	3.6% 1/28
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/29	6.7% 2/30	3.6% 1/28

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

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

Restriction type: LTE60