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

NCT01555099 | Completed Phase 2

• 2 other identifiers: D2340C000112011-005389-39
• Study Type: interventional
• Target: 353
• Locations: 8 countries
• Sites: 44

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD, FEV1, AZD5423

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Percent change from baseline in twenty-four hour plasma cortisol

  Baseline (week 0), and at week 4 and 12

• 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

• The percent change from baseline in pre-dose hsCRP at week 4 and 12

  Baseline(week 0), and at week 4 and 12

• 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

• Number of St George's Respiratory Questionnaire (SGRQ-C) responders and Overall Score

  Baseline(week 0), and at week 4 and 12

Study Arms (3)

AZD5423

EXPERIMENTAL

New study drug

Drug: AZD5423

Budesonide

ACTIVE COMPARATOR

Comparator to which the new study drug will be compared

Drug: Budesonide

Placebo

PLACEBO COMPARATOR

No drug to which both other arms will be compared

Drug: Placebo

Interventions

AZD5423 DRUG

oral inhaled

AZD5423

Budesonide DRUG

oral inhaled

Budesonide

Placebo DRUG

oral inhaled

Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (44)

Research Site

Doganovo, Bulgaria

Location

Research Site

Plovdiv, Bulgaria

Location

Research Site

Sofia, Bulgaria

Location

Research Site

Varna, Bulgaria

Location

Research Site

Brest, France

Location

Research Site

Marseille, France

Location

Research Site

Montpellier, France

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Nice, France

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Pessac, France

Location

Research Site

Balassagyarmat, Hungary

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Budapest, Hungary

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Deszk, Hungary

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Százhalombatta, Hungary

Location

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Foggia, FG, Italy

Location

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Padua, PD, Italy

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Verona, VR, Italy

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Napoli, Italy

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Pisa, Italy

Location

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Bialystok, Poland

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Gorzow Wlkp, Poland

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Lodz, Poland

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Proszowice, Poland

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Tarnów, Poland

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Barnaul, Russia, Russia

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Chelyabinsk, Russia

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Moscow, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Vladikavkaz, Russia

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Yaroslavl, Russia

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Yekaterinburg, Russia

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Vráble, Slovakia, Slovakia

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Bratislava, Slovakia

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Humenné, Slovakia

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Košice, Slovakia

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Spišská Nová Ves, Slovakia

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Zvolen, Slovakia

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Donetsk, Ukraine

Location

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Research Site

Kyiv, Ukraine

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Odesa, Ukraine

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Research Site

Poltava, Ukraine

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Research Site

Zaporizhzhya, Ukraine

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

2,2,2-trifluoro-N-(1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(3-methoxyphenyl)-2-propanyl)acetamide; Budesonide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Piotr Kuna, Professor

  Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego w Łodzi, ul. Kopcińskiego 22, 90-153, Łódź, Poland

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 14, 2012
• First Posted: March 15, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: June 17, 2013

Record last verified: 2013-06

Locations

IT (5); BU (4); PL (5); FR (5); HU (4); RU (8); SL (6); UA (7)