A Phase IIa Study to Investigate the Efficacy and Safety of AZD7624 in Chronic Obstructive Pulmonary Disease (COPD) Patients While on Maintenance Therapy
Condition: Chronic Obstructive Pulmonary Disease COPD
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: AZD7624 1.0 mg; Placebo
Intervention description: Inhaled AZD7624 solution, 11 mg/mL; Inhaled placebo solution
Intervention MeSH terms: AZD7624
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 213.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Pulmonary Disease; COPD patients; Exacerbations; ICS; LABA

Summary:

      The purpose of this study is to determine whether AZD7624 can reduce acute Chronic
      Obstructive Pulmonary Disease (COPD) exacerbations in patients on COPD maintenance therapy
      with a history of frequent acute exacerbations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of signed and dated written informed consent prior to any study specific
             procedures.

          -  Male and females aged 40-85 years. Females must have a negative pregnancy test at
             Visit 1, must not be lactating and must be of non-childbearing potential. Males must
             be surgically sterile or agree to use an acceptable method of contraception for the
             duration of the study and for 3 months after the last dose of investigational product
             to prevent pregnancy in a partner.

          -  A weight of ≥50 kg.

          -  Diagnosis of COPD for more than 1 year at Visit 1, according to the Global Initiative
             for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines.

          -  COPD maintenance treatment with at least ICS/LABA for at least 2 months prior to
             enrolment to be continued unchanged during the study.

          -  A post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator FEV1 ≤70% of the
             predicted normal value. Documented history of 2 or more moderate to severe COPD
             exacerbations within 12 months of randomisation, but not within the last 6 weeks
             before randomisation.

          -  Current or ex-smokers with a smoking history of at least 10 pack-years.

        Exclusion Criteria:

          -  Involvement in the planning and conduct of the study.

          -  Previous randomisation in the present study.

          -  Participation in another clinical study with any investigational medicinal product
             within 3 months of randomisation. Previously intake of any p38 inhibitor.

          -  Participation in, or scheduled for an intensive COPD rehabilitation programme at any
             time during the study.

          -  Planned in-patient surgery or hospitalisation during the study.

          -  Significant disease or disorder other than COPD which, 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. Asthma as a primary or main
             diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2013)
             or other accepted guidelines.

          -  A clinically relevant abnormal findings in clinical chemistry, haematology and
             urinalysis.

          -  Plasma myoglobin and CK above the upper reference range of the analysing laboratory at
             randomization.

          -  A clinically relevant abnormal findings in physical examination, pulse or blood
             pressure.

          -  A positive result on screening for serum hepatitis B hepatitis C and Human
             Immunodeficiency Virus (HIV).

          -  History or family history of muscle diseases. Abnormal vital signs, defined as
             Systolic Blood Pressure (SBP) above 140 mmHg if <60 years of age and above 150 mmHg if
             ≥60 years of age; Diastolic Blood Pressure (DBP) above 90 mmHg; Pulse <50 or >100 bpm.

          -  Prolonged QTcF >450 ms or family history of long QT syndrome or sudden death at young
             age. PR(PQ) interval of clinical significance, PR(PQ) > 250 ms.

          -  Intermittent AV block of 2nd and 3rd degree or AV dissociation.

          -  Patients with a QRS duration >120 ms.

          -  Patients with persistent, and/or recurrent symptomatic tachyarrhythmias, as well as
             patients with an implantable cardioverter-defibrillator (ICD) or a permanent
             pacemaker.

          -  Patients with recent Cardiovascular (CV) events or unstable CV disease or a myocardial
             infarction or stroke within 6 months of screening. History of hospitalization within
             12 months caused by heart failure or a diagnosis of heart failure higher than New York
             Heart Association (NYHA) class II.

          -  History of severe allergy/hypersensitivity or ongoing clinically important
             allergy/hypersensitivity or history of hypersensitivity to drugs with a similar
             chemical structure or class to AZD7624.

          -  Any exacerbation or respiratory infection within 6 weeks of randomization.

          -  Plasma donation within one month of Visit 1, or any blood donation/blood loss >500 mL
             during the 3 months prior to Visit 1.

          -  History of, or current alcohol or drug abuse.

          -  Treatment with any GCS (apart from prescribed steroids at run-in) within 6 weeks of
             Visit 3 regardless of indication.

          -  Treatment with strong CYP3A inhibitors within 4 weeks prior to randomisation.