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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01555099
• Other study ID #: D2340C00011
• Secondary ID: 2011-005389-39
• Status: Completed
• Phase: Phase 2
• First received: March 14, 2012
• Last updated: June 14, 2013
• Start date: April 2012
• Est. completion date: April 2013

Study information

• Verified date: June 2013
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• AZD5423
oral inhaled
• Budesonide
oral inhaled
• Placebo
oral inhaled

Locations

Country	Name	City	State
Bulgaria	Research Site	Doganovo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
France	Research Site	Brest Cedex 2
France	Research Site	Marseille Cedex 20
France	Research Site	Montpellier
France	Research Site	Nice Cedex 01
France	Research Site	Pessac
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Deszk
Hungary	Research Site	Szazhalombatta
Italy	Research Site	Foggia	FG
Italy	Research Site	Napoli
Italy	Research Site	Padova	PD
Italy	Research Site	Pisa
Italy	Research Site	Verona	VR
Poland	Research Site	Bialystok
Poland	Research Site	Gorzow Wlkp
Poland	Research Site	Lodz
Poland	Research Site	Proszowice
Poland	Research Site	Tarnow
Russian Federation	Research Site	Barnaul	Russia
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Yaroslavl
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Humenne
Slovakia	Research Site	Kosice
Slovakia	Research Site	Spisska Nova Ves
Slovakia	Research Site	Vrable
Slovakia	Research Site	Zvolen
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Ivano-frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Poltava
Ukraine	Research Site	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Bulgaria,  France,  Hungary,  Italy,  Poland,  Russian Federation,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change from baseline to mean of weeks 8 to 12 in pre-dose forced expiratory volume in 1 sec (FEV1)		Baseline (week 0), and at week 8, 10, and 12
Secondary	Percent change from baseline in twenty-four hour plasma cortisol		Baseline (week 0), and at week 4 and 12
Secondary	Time to first exacerbation (hospitalisation, oral/parenteral corticosteroid, oral/parenteral antibiotics)		Baseline(week 0) and week 2, 4, 8, 10, 12 and daily by eDairy
Secondary	The percent change from baseline in pre-dose hsCRP at week 4 and 12		Baseline(week 0), and at week 4 and 12
Secondary	Profile of pharmacokinetics (PK) of AZD5423 in terms of Cmax, tmax, AUC(0-24h), CL/F, Cav in subset of patients		Week 4 and 12
Secondary	Number of St George's Respiratory Questionnaire (SGRQ-C) responders and Overall Score		Baseline(week 0), and at week 4 and 12
Secondary	Assessment of Baseline/Transitional Dyspnea Index (BDI/TDI) Score		Baseline(week 0), and at week 4 and 12
Secondary	Assessment of Breathlessness, Cough and Sputum Scale (BCSS) Score		Daily by eDairy
Secondary	Absolute change from baseline to mean of week 2 and 4 pre-dose forced expiratory volume in 1 sec (FEV1)		Baseline (week 0), and at week 2 and 4.
Secondary	Absolute change from baseline in pre-dose FEV1		Baseline (week 0) and at week 2, 4, 8, 10 and 12