A 12-week Phase IIa, Double-blind, Placebo-controlled, Randomized Study to Investigate the Efficacy and Safety of AZD7624 in COPD Patients with a History of Frequent Acute Exacerbations while on Maintenance Therapy

Phase 2

Completed

Conditions: COPD
obstructive lung disease
10006436

Registration Number: NL-OMON41136

Lead Sponsor: Astra Zeneca

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

1. Provision of signed and dated written informed consent prior to any study specific procedures
2.. Male and females aged 40 - 85 years
3. Females must have a negative pregnancy test at Visit 1, must not be lactating and must be of non-childbearing potential, by fulfilling one of the following criteria:
-Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all possible exogenous hormonal treatments and luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range (at Visit 1)
-Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation;6. Clinical diagnosis of COPD for more than 1 year at Visit 1, according to the GOLD 2014 guidelines
7. Stable COPD maintenance treatment with at least ICS/LABA for at least 2 months prior to enrolment (Visit 1), to be continued unchanged during the study
8. A post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator FEV1 <=70% of the predicted normal value (at Visit 2)
9. Documented history of 2 or more moderate to severe COPD exacerbations (requiring treatment with systemic corticosteroid and/or with antibiotics and/or emergency room visit and/or hospitalisation) within 12 months of randomisation (Visit 3), but not within the last 6 weeks before randomisation (Visit 3). At least one of the exacerbations should be while on current COPD maintenance therapy (at least ICS/LABA)

Exclusion Criteria

1. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at third party vendor or at the investigational sites);2. Previous randomisation to treatment in the present study (at Visit 1);3. Participation in another clinical study with any novel investigational medicinal product within 3 months before the first dose of investigational product in this study (at Visit 3) ;4. Previously intake of any p38 inhibitor (same class as AZD7624);5. Participation in, or scheduled for an intensive COPD rehabilitation programme at any time during the study (N.B. patients are allowed to be in the maintenance phase of a rehabilitation programme);6. Planned in-patient surgery or hospitalisation during the study;7. Significant disease or disorder other than COPD (e.g. cardiovascular; pulmonary as e.g. tuberculosis and cystic fibrosis; gastrointestinal, liver; neurological; musculoskeletal; endocrine; metabolic; malignant; psychiatric; major physical impairment) which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient*s ability to participate in the study (at Visit 1) ;8. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2013) or other accepted guidelines. Patients with a past medical history of asthma (e.g. childhood or adolescence) may be included;9. Any clinically relevant abnormal findings in clinical chemistry, haematology and urinalysis, which, in the opinion of the investigator, may put the patient at risk because of participation in the study (at Visit 2 and 3);11. Any clinically relevant abnormal findings in physical examination, pulse or blood pressure which, in the opinion of the investigator, may put the patient at risk because of participation in the study (at Visit 1, 2 and 3);12. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV);13.History or family history of muscle diseases (at Visit 1);14.Abnormal vital signs, after 10 minutes supine rest, defined as any of the following (at Visit 1, 2 and 3):;*-Systolic blood pressure (SBP) above 150 mmHg;*-Diastolic blood pressure (DBP) above 90 mmHg;*-Pulse <40 or >100 bpm;15.Prolonged QTcF >450 ms or family history of long QT syndrome or sudden death at young age. PR(PQ) interval prolongation of clinical significance, PR(PQ) > 250 ms. Intermittent second or third degree atrioventricular (AV) block, or AV dissociation. QRS duration >=120ms. Patients who are not in sinus rhythm. Patients with persistent, and /or recurrent symptomatic tachyarrhythmias, as well as patients with an implantable cardioverter-defibrillator (ICD) or a permanent pacemaker. Patients on anticoagulation treatment.;16.Unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society (CSS) class 2. History of hospitalisation within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association (NYHA) class II. Acute myocardial infarction within 6 months of screening (Visit 1).;17. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD7624;18. Any exacerbation (defined as use o

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary outcome corresponding to this objective is thus the number of days<br /><br>to the first event during the 12-week treatment period. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Data will be summarised by treatment group and where applicable, by period<br /><br>and/or by visit. Summaries of the data will be produced using graphs and<br /><br>standard summary statistics. For continuous efficacy and vital signs<br /><br>variables, these statistics will include (but not be limited to) the number of<br /><br>non-missing values, the mean, SD, median, minimum and maximum. For categorical<br /><br>data, the statistics will consist of frequencies and associated percentages. </p><br>