Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD)Phase 2CIRRUSNCT01233232

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

A Phase 2 study testing AZD5069 50mg and AZD5069 80mg in people with Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD) and Laymen Terminology Chronic Bronchitis and Emphysema, run by AstraZeneca at 8 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is the evaluate the safety and tolerability of AZD5069 in patients with Chronic Obstructive Pulmonary Disease Read more about this study

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD), Laymen Terminology Chronic Bronchitis and Emphysema
What is being tested?: AZD5069 50mg and AZD5069 80mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 109 participants
Where: 8 sitesin 4 countries
Study dates: Nov 2010to Mar 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Clinical diagnosis of COPD with symptoms for more than one year before screening
Body mass index of 18-30 kg/m2 and weight of 50-100kg
Current or ex-smokers with a smoking history of at least 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for one year) at screening
FEV1 of 30% or above and less than 80% of the predicted normal value post-bronchodilator at screening
FEV1/FVC less than 70% post-bronchodilator at screening

Who cannot join

Any clinically significant disease or disorder
Exacerbation of COPD which was not resolved within 30 days of first dosing
Patients who have received live or live-attenuated vaccine in the 2 weeks prior to first dosing
Asthma and any current respiratory tract disorder other than COPD which is considered to be clinically significant
Disease history suggesting reduced or abnormal immune function other than that related to COPD

Trial locations and contacts

8 sites in 4 countries.

Country

City, postcode or hospital

8 sites in 4 countries

Hungary4 sites

Research Site
Debrecen
Research Site
Pécs
Research Site
Százhalombatta
Research Site
Szeged

Other trials in Hungary

Germany2 sites

Research Site
Berlin
Research Site
Großhansdorf

Other trials in Germany

Bulgaria1 site

Research Site
Sofia

Other trials in Bulgaria

Ukraine1 site

Research Site
Kyiv

Other trials in Ukraine

About this study

Official title: A 4 Week, Double Blind, Placebo Controlled, Randomised, Parallel Group, Multicentre, Phase IIa Study to Investigate the Safety and Tolerability of AZD5069 as Oral Capsules in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

The purpose of this study is the evaluate the safety and tolerability of AZD5069 in patients with Chronic Obstructive Pulmonary Disease

Conditions: Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD), Laymen Terminology Chronic Bronchitis and Emphysema
Being tested: Placebo, AZD5069 50mg, AZD5069 80mg
Keywords: Chronic Obstructive Pulmonary Disease, Neutrophil, Respiratory Disease
Medical subject headings: Emphysema, Pulmonary Disease, Chronic Obstructive, Respiration Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Oral dose bid
AZD5069 50mgDrug
Oral dose bid
AZD5069 80mgDrug
Oral dose bid

Study groups in NCT01233232
Study group	Role	What they receive
1	Placebo comparator	Placebo dose Receives: Drug: Placebo
2	Experimental	Treatment arm AZD5069 50mg Receives: Drug: AZD5069 50mg
3	Experimental	Treatment arm AZD5069 80mg Receives: Drug: AZD5069 80mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Patients Who Experienced at Least One Adverse Events(s)
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.
Measured: From start of treatment (Day 0) up to 28 days (End of Treatment)
Number of Participants With Abnormal Physical Examination Findings
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.
Measured: Last Observation on Treatment (up to Day 28)
Number of Participants With Abnormal Electrocardiogram (ECG)
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).
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)
The change in circulating leucocyte counts (including neutrophils) is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for Body Temperature
The change in body temperature (oral) is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs)
The change in systolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs)
The change in diastolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for Pulse Rate (Vital Signs)
The change in pulse rate (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test)
The change in FEV1 Pre-bronchodilator is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Change From Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test)
The change in FEV1 Post-bronchodilator is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Number of Participants Who Developed High Transaminase Values (Clinical Chemistry)
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).
Measured: Up to Follow-up Visit (3 to 18 days after End of Treatment [Day 28])
Change From Baseline to End of Treatment for Total Protein (Urinalysis)
The change in total protein in urine is calculated as the End of Treatment value minus the Baseline value.
Measured: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

Secondary outcomes (5)

Plasma Concentration of AZD5069 After 1 Hour of Dosing
At this visit, approximately 1 hour after dosing (at the clinic), a blood sample was collected for determination of drug concentration in plasma.
Measured: End of Treatment (Day 28), 1 hour after dosing
Area Under the Plasma Concentration Curve of AZD5069
The area under the plasma concentration curve is estimated from time 0 (dosing) to 24 hours after dosing.
Measured: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
Maximum Plasma Concentration for AZD5069
The maximum plasma concentration (Cmax) is the highest level of drug in plasma.
Measured: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
Time to Maximum Plasma Concentration for AZD5069
Time (in relation to dosing) at which the maximum plasma concentration is observed.
Measured: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
Maximum Reduction of Circulating Neutrophils in Blood, From Baseline
The change in circulating neutrophils in blood is calculated as the visit value minus the Baseline value. Only participants with reduction are considered.
Measured: Baseline (last non-missing assessment prior to first dose of study medication), weeks 1, 2 and 3, and End of Treatment (Day 28)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2010Mar 2011

First posted3 Nov 2010 (estimated)
Study startNov 2010
Primary completionMar 2011
Study completionMar 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD)Studies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 109 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01233232
Sponsor's protocol ID: D3550C00002
Other IDs: 2010-021217-23
Acronym: CIRRUS
Status last verified: Aug 2015
First submitted: 2 Nov 2010
Last updated: 17 Sep 2015
Results posted: Yes, on ClinicalTrials.gov

Publications

Kirsten AM, Forster K, Radeczky E, Linnhoff A, Balint B, Watz H, Wray H, Salkeld L, Cullberg M, Larsson B. The safety and tolerability of oral AZD5069, a selective CXCR2 antagonist, in patients with moderate-to-severe COPD. Pulm Pharmacol Ther. 2015 Apr;31:36-41. doi: 10.1016/j.pupt.2015.02.001. Epub 2015 Feb 11.
PubMed 25681277

Study at a glance

From the registry record, last updated by the sponsor on 17 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 4 Week, Double Blind, Placebo Controlled, Randomised, Parallel Group, Multicentre, Phase IIa Study to Investigate the Safety and Tolerability of AZD5069 as Oral Capsules in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
ClinicalTrials.gov ID: NCT01233232
Acronym / sponsor ID: CIRRUS / D3550C00002
Conditions: Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD), Laymen Terminology Chronic Bronchitis and Emphysema
Keywords: Chronic Obstructive Pulmonary Disease, Neutrophil, Respiratory Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 109 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Nov 2010
Primary completion: Mar 2011 (actual)
Study completion: Mar 2011 (actual)
First posted: 3 Nov 2010 (estimated)
Results: Posted 19 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is the evaluate the safety and tolerability of AZD5069 in patients with Chronic Obstructive Pulmonary Disease

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
1	Placebo comparator	Drug: PlaceboPlacebo dose
2	Experimental	Drug: AZD5069 50mgTreatment arm AZD5069 50mg
3	Experimental	Drug: AZD5069 80mgTreatment arm AZD5069 80mg

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Clinical diagnosis of COPD with symptoms for more than one year before screening
Body mass index of 18-30 kg/m2 and weight of 50-100kg
Current or ex-smokers with a smoking history of at least 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for one year) at screening
FEV1 of 30% or above and less than 80% of the predicted normal value post-bronchodilator at screening
FEV1/FVC less than 70% post-bronchodilator at screening

Key exclusion criteria (5 listed)

Any clinically significant disease or disorder
Exacerbation of COPD which was not resolved within 30 days of first dosing
Patients who have received live or live-attenuated vaccine in the 2 weeks prior to first dosing
Asthma and any current respiratory tract disorder other than COPD which is considered to be clinically significant
Disease history suggesting reduced or abnormal immune function other than that related to COPD

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboOral dose bid	Drug	1
AZD5069 50mgOral dose bid	Drug	2
AZD5069 80mgOral dose bid	Drug	3

Primary outcome

Patients Who Experienced at Least One Adverse Events(s)
Time frame: 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.
Number of Participants With Abnormal Physical Examination Findings
Time frame: 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.
Number of Participants With Abnormal Electrocardiogram (ECG)
Time frame: 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).
Change From Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)
Time frame: 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.
Change From Baseline to End of Treatment for Body Temperature
Time frame: 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.
Change From Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs)
Time frame: 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.
Change From Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs)
Time frame: 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.
Change From Baseline to End of Treatment for Pulse Rate (Vital Signs)
Time frame: 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.
Change From Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test)
Time frame: 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.
Change From Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test)
Time frame: 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.
Number of Participants Who Developed High Transaminase Values (Clinical Chemistry)
Time frame: 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).
Change From Baseline to End of Treatment for Total Protein (Urinalysis)
Time frame: 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.

5 secondary outcomes

Plasma Concentration of AZD5069 After 1 Hour of Dosing
Time frame: End of Treatment (Day 28), 1 hour after dosing
Area Under the Plasma Concentration Curve of AZD5069
Time frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
Maximum Plasma Concentration for AZD5069
Time frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
Time to Maximum Plasma Concentration for AZD5069
Time frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
Maximum Reduction of Circulating Neutrophils in Blood, From Baseline
Time frame: Baseline (last non-missing assessment prior to first dose of study medication), weeks 1, 2 and 3, and End of Treatment (Day 28)

Results and safety

Results posted to the registry on 19 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	29	28
AZD5069 50 mg	30	30
AZD5069 80 mg	28	28

Primary outcome: Patients Who Experienced at Least One Adverse Events(s)

Time frame: From start of treatment (Day 0) up to 28 days (End of Treatment). Number. Unit: Participants

Measure	Arm 1 - Placebo n = 29	Arm 2 - AZD5069 50 mg n = 30	Arm 3 - AZD5069 80 mg n = 28
Value	9	10	6

Primary outcome: Number of Participants With Abnormal Physical Examination Findings

Time frame: Last Observation on Treatment (up to Day 28). Number. Unit: Participants

Measure	Arm 1 - Placebo n = 29	Arm 2 - AZD5069 50 mg n = 30	Arm 3 - AZD5069 80 mg n = 28
Value	0	0	1

Primary outcome: Number of Participants With Abnormal Electrocardiogram (ECG)

Time frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28). Number. Unit: Participants

Measure	Arm 1 - Placebo n = 22	Arm 2 - AZD5069 50 mg n = 25	Arm 3 - AZD5069 80 mg n = 23
Value	0	0	0

Primary outcome: Change From Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)

Time frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28). Mean (Standard Deviation). Unit: 10^9/L cells/L

Measure	Arm 1 - Placebo n = 28	Arm 2 - AZD5069 50 mg n = 28	Arm 3 - AZD5069 80 mg n = 28
Value	-0.12 (1.974)	-1.55 (2.059)	-1.08 (2.404)

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 29 (0%)	3 of 29 (10.3%)	Not reported
AZD5069 50 mg	1 of 30 (3.3%)	8 of 30 (26.7%)	Not reported
AZD5069 80 mg	1 of 28 (3.6%)	1 of 28 (3.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25681277Kirsten AM, Forster K, Radeczky E, Linnhoff A, Balint B, Watz H, Wray H, Salkeld L, Cullberg M, Larsson B. The safety and tolerability of oral AZD5069, a selective CXCR2 antagonist, in patients with moderate-to-severe COPD. Pulm Pharmacol Ther. 2015 Apr;31:36-41. doi: 10.1016/j.pupt.2015.02.001. Epub 2015 Feb 11.
D3550C00002\_Revised\_Clinical\_Study\_Protocol.pdfLink provided by the sponsor.
D3550C00002\_Study\_Synopsis.pdfLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

8 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Hungary, Germany, Bulgaria, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patients Who Experienced at Least One Adverse Events(s) (time frame: From start of treatment (Day 0) up to 28 days (End of Treatment)). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01233232, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2015.