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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01233232
First received: November 2, 2010
Last updated: April 30, 2015
Last verified: April 2015
  Purpose

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


Condition Intervention Phase
Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD)
Laymen Terminology Chronic Bronchitis and Emphysema
Drug: Placebo
Drug: AZD5069 50mg
Drug: AZD5069 80mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Patients Who Experienced at Least One Adverse Events(s) [ Time Frame: From start of treatment (Day 0) up to 28 days (End of Treatment) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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]) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    The change in total protein in urine is calculated as the End of Treatment value minus the Baseline value.


Secondary Outcome Measures:
  • Plasma Concentration of AZD5069 After 1 Hour of Dosing [ Time Frame: End of Treatment (Day 28), 1 hour after dosing ] [ Designated as safety issue: No ]
    At this visit, approximately 1 hour after dosing (at the clinic), a blood sample was collected for determination of drug concentration in plasma.

  • 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      ] [ Designated as safety issue: No ]
    The area under the plasma concentration curve is estimated from time 0 (dosing) to 24 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 ] [ Designated as safety issue: No ]
    The maximum plasma concentration (Cmax) is the highest level of drug in plasma.

  • Time to Maximum Plasma Concentration for AZD5069 [ Time Frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing ] [ Designated as safety issue: No ]
    Time (in relation to dosing) at which the maximum plasma concentration is observed.

  • 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) ] [ Designated as safety issue: Yes ]
    The change in circulating neutrophils in blood is calculated as the visit value minus the Baseline value. Only participants with reduction are considered.


Enrollment: 109
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Placebo dose
Drug: Placebo
Oral dose bid
Experimental: 2
Treatment arm AZD5069 50mg
Drug: AZD5069 50mg
Oral dose bid
Experimental: 3
Treatment arm AZD5069 80mg
Drug: AZD5069 80mg
Oral dose bid

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01233232

Locations
Bulgaria
Research Site
Sofia, Bulgaria
Germany
Research Site
Berlin, Germany
Research Site
GROßHANSDORF, Germany
Hungary
Research Site
Debrecen, Hungary
Research Site
Pécs, Hungary
Research Site
Szeged, Hungary
Research Site
Százhalombatta, Hungary
Ukraine
Research Site
Kyiv, Ukraine
Sponsors and Collaborators
AstraZeneca
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01233232     History of Changes
Other Study ID Numbers: D3550C00002, 2010-021217-23
Study First Received: November 2, 2010
Results First Received: April 30, 2015
Last Updated: April 30, 2015
Health Authority: Bulgaria: Bulgarian Drug Agency
Germany: National Regulatory Authority - BfArM (Bundesinstitut fur Arzneimittel und Medizinpordukte)
Hungary: National Institute of Pharmacy
Ukraine: Ministry of Healthcare of Ukraine The State Pharmacological Centre of Ministry of Health

Keywords provided by AstraZeneca:
Chronic Obstructive Pulmonary Disease, Neutrophil, Respiratory Disease

Additional relevant MeSH terms:
Bronchitis
Bronchitis, Chronic
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on July 01, 2015