Clinical trial NCT01543919: Study To Evaluate The Efficacy And Safety Of PH-797804 For 12 Weeks In Adults With Moderate To Severe Chronic Obstructive Pulmonary Disease (COPD) On A Background Of Tiotropium Bromide
Official title: A Phase 2B, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of Once-Daily Orally Administered PH-797804 For 12 Weeks In Adults With Moderate To Severe Chronic Obstructive Pulmonary Disease (COPD) On A Background Of Tiotropium Bromide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-03-05
Enrollment: 730
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PH-797804 is an oral anti-inflammatory drug that may reduce the inflammation that is associated with Chronic Obstructive Pulmonary Disease (COPD). PH-797804 will be dosed to patients with Chronic Obstructive Pulmonary Disease (COPD) to evaluate its potential safety and efficacy profile in Chronic Obstructive Pulmonary Disease (COPD)


Eligibility criteria: Inclusion Criteria:

* Male or female subjects between, and including, the ages of 40 and 80 years.
* Subjects with a diagnosis, for at least 6 months, of moderate to severe COPD (GOLD) and who meet the criteria for Stage II-III disease: Subjects must have a post-bronchodilator FEV1/FVC ratio \<0.7 and a post-bronchodilator FEV1 of 30 - 80% (inclusive) of the predicted value for age, height, race and sex using European Community for Coal and Steel ECCS standards or NHANES III standards.
* Subjects must have a smoking history of at least 10 pack-years\* and meet one of the following criteria: They are current smokers, or they are ex-smokers who have abstained from smoking for at least 6 months.
* Subjects treated with tiotropium bromide (SPIRIVA HandiHaler) 18 microgram daily for at least 1 month prior to screening.
* Subjects must have had stable disease for at least 1 month prior to screening. During the screening and run-in phase subjects must be able to manage disease symptoms adequately with tiotropium bromide +/- salbutamol (albuterol) rescue medication (subjects should not use \>10 actuations \[100 microgram/actuations\] daily for more than 2 consecutive days), without reliance on other therapies including oral or inhaled corticosteroids, other long-acting bronchodilators, nebulizer therapy, theophylline, roflumilast or regular oxygen.

Exclusion Criteria:

* A COPD exacerbation requiring treatment with oral steroids or hospitalization for the treatment of COPD within 3 months of screening.
* History of a lower respiratory tract infection or significant disease instability during the month preceding screening or during the time between screening and randomization.
* History or presence of respiratory failure, cor pulmonale or right ventricular failure.
* Subjects with home oxygen therapy (either PRN or long-term oxygen therapy).
* Any clearly documented history of adult asthma or other chronic respiratory disorders (eg, bronchiectasis, pulmonary fibrosis, pneumoconiosis).
* Known previous diagnosis of Hepatitis B or C or HIV infection (specific screening is not required).
* History of cancer (other than cutaneous basal cell) in the previous 5 years.
* Active or past history of GI hemorrhage of any etiology, peptic ulceration, erosive esophagitis, gastric outlet obstruction or inflammatory bowel disease.
* Regular use of aspirin at a dose greater than 325 mg/day.
* History within the previous 6 months of: myocardial infarction, cardiac arrhythmia (eg, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia), left ventricular failure, unstable angina, coronary angioplasty, coronary artery bypass grafting (CABG) or cerebrovascular accident (including transient ischemic attacks).
* A family history of long QT syndrome.
* Presenting with: Any condition possibly affecting oral drug absorption (eg, gastrectomy or clinically significant diabetic gastroenteropathy).
* Any clinically significant skin lesions as described in Common Terminology Criteria for Adverse Events for Dermatology (CTCAE) Version 3.0.
* Any clinically significant active systemic or cutaneous infection including herpetic lesions.
* Congestive heart failure requiring treatment New York Heart Association (NYHA) Class III-IV.
* ECG abnormalities at screening or randomization, including those listed below: Subjects with pre-randomization evidence of QTcF prolongation (defined as \>450 ms) at screening or baseline (Week 0) are not eligible for randomization. This assessment is based on a confirmed mean of the triplicate ECG recordings and is made by the investigator at the time of ECG collection.
* Predominant heart rhythm other than normal sinus rhythm eg, atrial fibrillation, atrial flutter, supraventricular tachycardia.
* Atrioventricular (AV) block greater than first degree.
* Resting heart rate \>100 or \<40 bpm.
* Evidence of previous myocardial infarction in the absence of clinical history consistent with these findings.
* Evidence of acute ischemia.

Primary outcomes:
measure: Change from baseline in trough (pre-treatment and pre-bronchodilator) Forced Expiratory Volume1 at Week 12.
timeFrame: Baseline, week 12
Secondary outcomes:
measure: Change from baseline in trough, pre-bronchodilator Forced Expiratory Volume1 at Weeks 2, 6, and 10
timeFrame: Baseline, week 2, 6, and 10
measure: Change from baseline in trough, pre-bronchodilator Forced Expiratory Volume6 at Weeks 2, 6, 10 and 12
timeFrame: Baseline, week 2, 6, 10 and 12
measure: Change from baseline in trough, pre-bronchodilator Forced Vital Capacity at Weeks 2, 6, 10 and 12
timeFrame: Baseline, week 2, 6, 10 and 12
measure: Change from baseline in trough, pre-bronchodilator Inspiratory Capacity at Weeks 2, 6, 10 and 12
timeFrame: Baseline, week 2, 6, 10 and 12
measure: Average change from baseline in trough, pre-bronchodilator Forced Expiratory Volume 1, Forced Expiratory Volume 6, Forced Vital Capacity and Inspiratory Capacity over 12 weeks treatment
timeFrame: Baseline, week 12
measure: Change from baseline in post-study drug, pre-bronchodilator Forced Expiratory Volume1, Forced Expiratory Volume6, Forced Vital Capacity and Inspiratory Capacity at Weeks 0 and 12
timeFrame: Baseline, week 0, 12
measure: Change from baseline in post-study drug, post-bronchodilator Forced Expiratory Volume1, Forced Expiratory Volume6, Forced Vital Capacity and Inspiratory Capacity at Weeks 0 and 12
timeFrame: Baseline, week 0, week 12
measure: Change from baseline in Chronic Obstructive Pulmonary Disease symptoms (EXACT-PRO Daily Diary) over 12 weeks treatment.
timeFrame: Baseline, week 12
measure: Change from baseline in Chronic Respiratory Questionnaire - Self Administered Standard (CRQ-SAS) at Weeks 2, 6, 10 and 12
timeFrame: Baseline, week 2, 4, 6, 10 and 12
measure: Patient Global Impression of Change at Week 12
timeFrame: Baseline, week 12
measure: Change from baseline (Baseline Dyspnea Index) in dyspnea (Transition Dyspnea Index) at Weeks 2, 6, 10 and 12
timeFrame: Baseline, week 2, 4, 6, 10, and 12
measure: Clinician Global Impression of Change at Week 12
timeFrame: Baseline, week 12
measure: Rescue bronchodilator use (per daily diary) over 12 weeks of therapy
timeFrame: Baseline, week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Jasper
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: Pfizer Investigational Site
state: Arizona
city: Montclair
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: Waterbury
country: United States
facility: Pfizer Investigational Site
state: Connecticut
city: Newark
country: United States
facility: Pfizer Investigational Site
state: Delaware
city: Brandon
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Chiefland
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Chiefland
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Pfizer Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Pensacola
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Tampa
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Williston
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Duluth
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Fort Mitchell
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Edina
country: United States
facility: Pfizer Investigational Site
state: Minnesota
city: Fridley
country: United States
facility: Pfizer Investigational Site
state: Minnesota
city: Minneapolis
country: United States
facility: Pfizer Investigational Site
state: Minnesota
city: Rochester
country: United States
facility: Pfizer Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Albuquerque
country: United States
facility: Pfizer Investigational Site
state: New Mexico
city: Albuquerque
country: United States
facility: Pfizer Investigational Site
state: New Mexico
city: Albuquerque
country: United States
facility: Pfizer Investigational Site
state: New Mexico
city: Rochester
country: United States
facility: Pfizer Investigational Site
state: New York
city: Charlotte
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Pfizer Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Pawtucket
country: United States
facility: Pfizer Investigational Site
state: Rhode Island
city: Warwick
country: United States
facility: Pfizer Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Charleston
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Kingsport
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Midvale
country: United States
facility: Pfizer Investigational Site
state: Utah
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Ruse
country: Bulgaria
facility: Pfizer Investigational Site
city: Sevlievo
country: Bulgaria
facility: Pfizer Investigational Site
city: Sofia
country: Bulgaria
facility: Pfizer Investigational Site
city: Sofia
country: Bulgaria
facility: Pfizer Investigational Site
city: Stara Zagora
country: Bulgaria
facility: Pfizer Investigational Site
city: Troyan
country: Bulgaria
facility: Pfizer Investigational Site
city: Veliko Tarnovo
country: Bulgaria
facility: Pfizer Investigational Site
city: Winnipeg
country: Canada
facility: Pfizer Investigational Site
state: Manitoba
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: St-Romuald
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: Pfizer Investigational Site
city: Karlovy Vary
country: Czech Republic
facility: Pfizer Investigational Site
city: Liberec
country: Czech Republic
facility: Pfizer Investigational Site
city: Melnik
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 10
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 5
country: Czech Republic
facility: Pfizer Investigational Site
city: Rokycany
country: Czech Republic
facility: Pfizer Investigational Site
city: Teplice
country: Czech Republic
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Dresden
country: Germany
facility: Pfizer Investigational Site
city: Gelnhausen
country: Germany
facility: Pfizer Investigational Site
city: Grosshansdorf
country: Germany
facility: Pfizer Investigational Site
city: Hamburg
country: Germany
facility: Pfizer Investigational Site
city: Hamburg
country: Germany
facility: Pfizer Investigational Site
city: Hannover
country: Germany
facility: Pfizer Investigational Site
city: Kassel
country: Germany
facility: Pfizer Investigational Site
city: Luebeck
country: Germany
facility: Pfizer Investigational Site
city: Schwerin
country: Germany
facility: Pfizer Investigational Site
city: Balassagyarmat
country: Hungary
facility: Pfizer Investigational Site
city: Budaors
country: Hungary
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Debrecen
country: Hungary
facility: Pfizer Investigational Site
city: Szeged
country: Hungary
facility: Pfizer Investigational Site
city: Szombathely
country: Hungary
facility: Pfizer Investigational Site
city: Torokbalint
country: Hungary
facility: Pfizer Investigational Site
city: Seto-shi
country: Japan
facility: Pfizer Investigational Site
state: Aichi-ken
city: Nagoya
country: Japan
facility: Pfizer Investigational Site
state: Aichi
city: Toyota
country: Japan
facility: Pfizer Investigational Site
state: Aichi
city: Noda
country: Japan
facility: Pfizer Investigational Site
state: Chiba
city: Yanagawa
country: Japan
facility: Pfizer Investigational Site
state: Fukuoka
city: Kanazawa
country: Japan
facility: Pfizer Investigational Site
state: Ishikawa
city: Takamatsu
country: Japan
facility: Pfizer Investigational Site
state: Kagawa
city: Kawasaki-shi
country: Japan
facility: Pfizer Investigational Site
state: Kanagawa
city: Zama
country: Japan
facility: Pfizer Investigational Site
state: Kanagawa
city: Saiki
country: Japan
facility: Pfizer Investigational Site
state: Oita
city: Meguro-ku
country: Japan
facility: Pfizer Investigational Site
state: Tokyo
city: Setagaya
country: Japan
facility: Pfizer Investigational Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Pfizer Investigational Site
city: Kumamoto
country: Japan
facility: Pfizer Investigational Site
city: Osaka
country: Japan
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Wroclaw
country: Poland
facility: Pfizer Investigational Site
city: Wroclaw
country: Poland
facility: Pfizer Investigational Site
city: Bardejov
country: Slovakia
facility: Pfizer Investigational Site
city: Bojnice
country: Slovakia
facility: Pfizer Investigational Site
city: Bratislava
country: Slovakia
facility: Pfizer Investigational Site
city: Bratislava
country: Slovakia
facility: Pfizer Investigational Site
city: Humenne
country: Slovakia
facility: Pfizer Investigational Site
city: Kosice
country: Slovakia
facility: Pfizer Investigational Site
city: Liptovsky Hradok
country: Slovakia
facility: Pfizer Investigational Site
city: Namestovo
country: Slovakia
facility: Pfizer Investigational Site
city: Poprad
country: Slovakia
facility: Pfizer Investigational Site
city: Spisska Nova Ves
country: Slovakia
facility: Pfizer Investigational Site
city: Sturovo
country: Slovakia
facility: Pfizer Investigational Site
city: Bloemfontein
country: South Africa
facility: Pfizer Investigational Site
state: Free State
city: Gatesville
country: South Africa
facility: Pfizer Investigational Site
state: Western Cape
city: Parow
country: South Africa
facility: Pfizer Investigational Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Pfizer Investigational Site
city: Cape Town
country: South Africa
facility: Pfizer Investigational Site
city: Durban
country: South Africa
facility: Pfizer Investigational Site
city: Durban
country: South Africa
facility: Pfizer Investigational Site
city: Pretoria
country: South Africa
facility: Pfizer Investigational Site
city: Petrer
country: Spain
facility: Pfizer Investigational Site
state: Alicante
city: Merida
country: Spain
facility: Pfizer Investigational Site
state: Badajoz
city: Salt
country: Spain
facility: Pfizer Investigational Site
state: Girona
city: Pozuelo de Alarcon
country: Spain
facility: Pfizer Investigational Site
state: Madrid
city: Goteborg
country: Sweden
facility: Pfizer Investigational Site
city: Linkoping
country: Sweden
facility: Pfizer Investigational Site
city: Lund
country: Sweden
facility: Pfizer Investigational Site
city: Malmo
country: Sweden
facility: Pfizer Investigational Site
city: Skene
country: Sweden
facility: Pfizer Investigational Site
city: Taipei
country: Taiwan
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: