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

NCT01233232 | Completed Phase 2 Results

• 2 other identifiers: D3550C000022010-021217-23
• Study Type: interventional
• Target: 109
• Locations: 4 countries
• Sites: 8

Brief Summary

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

Keywords

Chronic Obstructive Pulmonary Disease, Neutrophil, Respiratory Disease

Outcome Measures

Primary Outcomes (12)

• 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.

  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.

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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.

  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

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

• Area Under the Plasma Concentration Curve of AZD5069

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

• Maximum Plasma Concentration for AZD5069

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

• Time to Maximum Plasma Concentration for AZD5069

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

• Maximum Reduction of Circulating Neutrophils in Blood, From Baseline

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

Study Arms (3)

1

PLACEBO COMPARATOR

Placebo dose

Drug: Placebo

2

EXPERIMENTAL

Treatment arm AZD5069 50mg

Drug: AZD5069 50mg

3

EXPERIMENTAL

Treatment arm AZD5069 80mg

Drug: AZD5069 80mg

Interventions

Placebo DRUG

Oral dose bid

1

AZD5069 50mg DRUG

Oral dose bid

2

AZD5069 80mg DRUG

Oral dose bid

3

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (8)

Research Site

Sofia, Bulgaria

Location

Research Site

Berlin, Germany

Location

Research Site

Großhansdorf, Germany

Location

Research Site

Debrecen, Hungary

Location

Research Site

Pécs, Hungary

Location

Research Site

Százhalombatta, Hungary

Location

Research Site

Szeged, Hungary

Location

Research Site

Kyiv, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 25681277 BACKGROUND

Related Links

• D3550C00002\_Revised\_Clinical\_Study\_Protocol.pdf
• D3550C00002\_Study\_Synopsis.pdf

MeSH Terms

Conditions

Emphysema; Pulmonary Disease, Chronic Obstructive; Respiration Disorders

Interventions

N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 3, 2010
• Study Start: November 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: September 17, 2015
• Results First Posted: May 19, 2015

Record last verified: 2015-08

Locations

BU (1); DE (2); HU (4); UA (1)