A Phase IIa Study to Investigate the Efficacy and Safety of AZD7624 in Chronic Obstructive Pulmonary Disease (COPD) Patients While on Maintenance Therapy

Chronic Obstructive Pulmonary Disease COPD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02238483
• Other study ID #: D2550C00005
• Secondary ID: 2014-001053-16
• Status: Completed
• Phase: Phase 2
• Start date: October 28, 2014
• Est. completion date: April 4, 2016

Study information

• Verified date: April 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: April 4, 2016
• Est. primary completion date: April 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• AZD7624 1.0 mg
Inhaled AZD7624 solution, 11 mg/mL
• Placebo
Inhaled placebo solution

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autónoma de Bs. As.
Argentina	Research Site	Quilmes
Argentina	Research Site	San Miguel de Tucuman
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talca
Chile	Research Site	Talcahuano
Netherlands	Research Site	Assen
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Nijmegen
Netherlands	Research Site	Zutphen
Peru	Research Site	Lima
Peru	Research Site	Lima
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Mount Edgecombe
South Africa	Research Site	Parktown West
United States	Research Site	Akron	Ohio
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Blue Ridge	Georgia
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Dayton	Ohio
United States	Research Site	Denver	Colorado
United States	Research Site	Erie	Pennsylvania
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hialeah	Florida
United States	Research Site	Kingwood	Texas
United States	Research Site	Larchmont	New York
United States	Research Site	Los Angeles	California
United States	Research Site	Miami	Florida
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Torrance	California
United States	Research Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Netherlands,  Peru,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)	For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.; Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)	For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.; Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Time to First Moderate or Severe Exacerbation		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Annual Exacerbation Rate of Moderate and Severe Exacerbations	For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.; Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)	For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.; Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)	For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.; Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)	The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])	The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Dyspnea (Transitional Dyspnea Index (TDI) Score)	The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference.	Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Secondary	Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio		Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)