Multi-centre Study to Assess the Efficacy and Safety of AZD5423 in COPD Patients on a Background Therapy of Formoterol

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01555099
First received: March 14, 2012
Last updated: June 14, 2013
Last verified: June 2013
  Purpose

The purpose of the study is to assess the efficacy and safety of two staggered dose levels of inhaled once daily AZD5423 or twice daily budesonide for 12 weeks in COPD patients on a background therapy of formoterol.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: AZD5423
Drug: Budesonide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase-II, Double-blind, Placebo-controlled, Randomised, Parallel-group,Multi-centre Study to Assess the Efficacy and Safety of Two Staggered Dose Levels of Inhaled Once Daily AZD5423 or Twice Daily Budesonide for 12 Weeks in COPD Patients on a Background Therapy of Formoterol.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Absolute change from baseline to mean of weeks 8 to 12 in pre-dose forced expiratory volume in 1 sec (FEV1) [ Time Frame: Baseline (week 0), and at week 8, 10, and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent change from baseline in twenty-four hour plasma cortisol [ Time Frame: Baseline (week 0), and at week 4 and 12 ] [ Designated as safety issue: Yes ]
  • Time to first exacerbation (hospitalisation, oral/parenteral corticosteroid, oral/parenteral antibiotics) [ Time Frame: Baseline(week 0) and week 2, 4, 8, 10, 12 and daily by eDairy ] [ Designated as safety issue: No ]
  • The percent change from baseline in pre-dose hsCRP at week 4 and 12 [ Time Frame: Baseline(week 0), and at week 4 and 12 ] [ Designated as safety issue: Yes ]
  • Profile of pharmacokinetics (PK) of AZD5423 in terms of Cmax, tmax, AUC(0-24h), CL/F, Cav in subset of patients [ Time Frame: Week 4 and 12 ] [ Designated as safety issue: No ]
  • Number of St George's Respiratory Questionnaire (SGRQ-C) responders and Overall Score [ Time Frame: Baseline(week 0), and at week 4 and 12 ] [ Designated as safety issue: No ]
  • Assessment of Baseline/Transitional Dyspnea Index (BDI/TDI) Score [ Time Frame: Baseline(week 0), and at week 4 and 12 ] [ Designated as safety issue: No ]
  • Assessment of Breathlessness, Cough and Sputum Scale (BCSS) Score [ Time Frame: Daily by eDairy ] [ Designated as safety issue: No ]
  • Absolute change from baseline to mean of week 2 and 4 pre-dose forced expiratory volume in 1 sec (FEV1) [ Time Frame: Baseline (week 0), and at week 2 and 4. ] [ Designated as safety issue: No ]
  • Absolute change from baseline in pre-dose FEV1 [ Time Frame: Baseline (week 0) and at week 2, 4, 8, 10 and 12 ] [ Designated as safety issue: No ]

Enrollment: 353
Study Start Date: April 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD5423
New study drug
Drug: AZD5423
oral inhaled
Other Name: AZD5423
Active Comparator: Budesonide
Comparator to which the new study drug will be compared
Drug: Budesonide
oral inhaled
Other Name: Budesonide
Placebo Comparator: Placebo
No drug to which both other arms will be compared
Drug: Placebo
oral inhaled
Other Name: Placebo

Detailed Description:

A phase-II, double-blind, placebo-controlled, randomised, parallel-group,multi-centre study to assess the efficacy and safety of two staggered dose levels of inhaled once daily AZD5423 or twice daily budesonide for 12 weeks in COPD patients on a background therapy of formoterol.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed and dated informed consent prior to conducting any study specific procedures
  • Men or women aged ≥ 40 years
  • Men or post-menopausal or surgically sterile women. Women will be considered post-menopausal if they have been amenorrheic for at least 12 months, and have a follicle stimulating hormone (FSH) plasma concentration within the postmenopausal range as defined by the laboratory. Male patients should be willing to use barrier contraception, i.e. condom (with spermicide) from the day of dosing until at least 5 weeks after the last dose with the study drug.
  • Clinical diagnosis of COPD for more than 1 year at Visit 1, according to GOLD guidelines
  • Current maintenance therapy with LABA and/or LAMA, ICS/LABA or ICS plus LAMA combination
  • Current or ex-smokers with a smoking history equivalent to at least 10 pack years (1 pack year = 20 cigarettes smoked per day for one year)
  • Post-bronchodilator FEV1 ≥40 and ≤ 80% of the predicted normal value
  • Post-bronchodilator FEV1/FVC <0,7
  • Reversibility of airway obstruction according to reversibility test performed at visit 2, defined as an increase in FEV1 of ≥10% relative baseline after inhalation of in total 400 μg salbutamol or 1 mg terbutaline sulphate
  • Chest radiography (not older than 12 months at Visit 2) not showing any pathological changes that would make the patient unsuitable for inclusion as judged by the Investigator
  • Able to read and write and use the electronic devices (eDiary and electronic spirometry)
  • Ability to complete an eDiary correctly. Baseline diary data had to be recorded for at least 8 (any 8) of the last 10 days of the run-in period to accept patients for randomized treatment (Randomisation Criteria at Visit 3).
  • Provision of informed consent for genetic sampling and analyses. If a patient declines to participate in the pharmacogenetic research, there will be no consequence or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in the Clinical Study Protocol (CSP), as long as they consent (Inclusion criteria for patients taking part in the pharmacogenetic research)

Exclusion Criteria:

  • Significant disease or disorder (eg, cardiovascular, pulmonary other than COPD, gastrointestinal, liver, renal, 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
  • Any clinically relevant abnormal findings in clinical chemistry, haematology, urinalysis, physical examination, pulse, blood pressure or ECG at Visit 2, which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study
  • Requirement for long term oxygen therapy
  • An exacerbation of COPD, defined as use of oral or parenteral glucocorticosteroids or oral/parenteral antibiotics or hospitalisation related to COPD within 6 weeks of Visit 2
  • Participation in or scheduled for an intensive COPD rehabilitation program
  • Known or suspected hypersensitivity to study therapy or excipients of the study drug
  • History of current alcohol or drug abuse or any condition associated with poor compliance as judged by the investigator
  • Plasma donation within one month of screening or any blood donation/blood loss >500 mL during the 3 months prior to screening.
  • Participation in any clinical study with an investigational drug or new formulation of a marketed drug in the 3 months prior to Visit 2
  • Planned in-patient surgery or hospitalisation during the study
  • Previous randomisation of treatment into the present study
  • Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
  • Previous allogeneic bone marrow transplant (Exclusion criteria for patients taking part in the pharmacogenetic research)
  • Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection (Exclusion criteria for patients taking part in the pharmacogenetic research)
  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: NCT01555099

  Show 44 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Piotr Kuna, Professor Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego w Łodzi, ul. Kopcińskiego 22, 90-153, Łódź, Poland
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01555099     History of Changes
Other Study ID Numbers: D2340C00011, 2011-005389-39
Study First Received: March 14, 2012
Last Updated: June 14, 2013
Health Authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Russia: Ethics Committee
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ministry of Health
Ukraine: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
Slovakia: State Institute for Drug Control
France: Direction Générale de la Santé
France: French Data Protection Authority
France: Haute Autorité de Santé Transparency Commission
France: Institutional Ethical Committee
France: Ministry of Health
France: National Consultative Ethics Committee for Health and Life Sciences
Italy: Ethics Committee
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Hungary: National Institute of Pharmacy
Hungary: Medical Research Council Ethics Committee for Clinical Pharmacology

Keywords provided by AstraZeneca:
COPD, FEV1, AZD5423

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Budesonide
Formoterol
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014