Clinical trial NCT02238483: A Phase IIa Study to Investigate the Efficacy and Safety of AZD7624 in Chronic Obstructive Pulmonary Disease (COPD) Patients While on Maintenance Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease COPD
Keywords: Chronic Obstructive Pulmonary Disease
COPD patients
Exacerbations
ICS
LABA
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-09-12
Enrollment: 213
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms
timeFrame: 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 outcomes:
measure: Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)
timeFrame: 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)
measure: Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)
timeFrame: 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)
measure: Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)
timeFrame: 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)
measure: Time to First Moderate or Severe Exacerbation
timeFrame: 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)
measure: Annual Exacerbation Rate of Moderate and Severe Exacerbations
timeFrame: 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)
measure: Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)
timeFrame: 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)
measure: Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)
timeFrame: 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)
measure: Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)
timeFrame: 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)
measure: Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)
timeFrame: 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)
measure: Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)
timeFrame: 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)
measure: Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])
timeFrame: 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)
measure: Dyspnea (Transitional Dyspnea Index (TDI) Score)
timeFrame: 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)
measure: Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 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)
measure: Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)
timeFrame: 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)
measure: Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Blue Ridge
country: United States
facility: Research Site
state: Georgia
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Larchmont
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Erie
country: United States
facility: Research Site
state: Pennsylvania
city: Gaffney
country: United States
facility: Research Site
state: South Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Kingwood
country: United States
facility: Research Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Ciudad Autónoma de Bs. As.
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Talcahuano
country: Chile
facility: Research Site
city: Talca
country: Chile
facility: Research Site
city: Assen
country: Netherlands
facility: Research Site
city: Heerlen
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Zutphen
country: Netherlands
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Amanzimtoti
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Mount Edgecombe
country: South Africa
facility: Research Site
city: Parktown West
country: South Africa
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D Boston
name: Naimish Patel, MD, PhD
role: STUDY_DIRECTOR
affiliation: National Jewish Health, Denver, United States
name: Barry Make, MD, FCCP, FACVPR
role: PRINCIPAL_INVESTIGATOR
References: