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

Pulmonary Disease, Chronic Obstructive Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01543919
• Other study ID #: A6631033
• Status: Completed
• Phase: Phase 2
• First received: February 28, 2012
• Last updated: October 15, 2014
• Start date: April 2012
• Est. completion date: September 2013

Study information

• Verified date: September 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 730
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• PH-797804
0.25 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
• PH-797804
1 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
• PH-797804
3 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
• PH-797804
6 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
• PH-797804
10 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
• Placebo
Placebo oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Bulgaria	Pfizer Investigational Site	Ruse
Bulgaria	Pfizer Investigational Site	Sevlievo
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Stara Zagora
Bulgaria	Pfizer Investigational Site	Troyan
Bulgaria	Pfizer Investigational Site	Veliko Tarnovo
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Sherbrooke	Quebec
Canada	Pfizer Investigational Site	St-Romuald	Quebec
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Winnipeg	Manitoba
Czech Republic	Pfizer Investigational Site	Karlovy Vary
Czech Republic	Pfizer Investigational Site	Liberec
Czech Republic	Pfizer Investigational Site	Melnik
Czech Republic	Pfizer Investigational Site	Praha 10
Czech Republic	Pfizer Investigational Site	Praha 5
Czech Republic	Pfizer Investigational Site	Rokycany
Czech Republic	Pfizer Investigational Site	Teplice
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Dresden
Germany	Pfizer Investigational Site	Gelnhausen
Germany	Pfizer Investigational Site	Grosshansdorf
Germany	Pfizer Investigational Site	Hamburg
Germany	Pfizer Investigational Site	Hamburg
Germany	Pfizer Investigational Site	Hannover
Germany	Pfizer Investigational Site	Kassel
Germany	Pfizer Investigational Site	Luebeck
Germany	Pfizer Investigational Site	Schwerin
Hungary	Pfizer Investigational Site	Balassagyarmat
Hungary	Pfizer Investigational Site	Budaors
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Debrecen
Hungary	Pfizer Investigational Site	Szeged
Hungary	Pfizer Investigational Site	Szombathely
Hungary	Pfizer Investigational Site	Torokbalint
Japan	Pfizer Investigational Site	Fukuoka
Japan	Pfizer Investigational Site	Kanazawa	Ishikawa
Japan	Pfizer Investigational Site	Kawasaki-shi	Kanagawa
Japan	Pfizer Investigational Site	Kumamoto
Japan	Pfizer Investigational Site	Meguro-ku	Tokyo
Japan	Pfizer Investigational Site	Nagoya	Aichi
Japan	Pfizer Investigational Site	Noda	Chiba
Japan	Pfizer Investigational Site	Osaka
Japan	Pfizer Investigational Site	Saiki	Oita
Japan	Pfizer Investigational Site	Setagaya	Tokyo
Japan	Pfizer Investigational Site	Seto-shi	Aichi-ken
Japan	Pfizer Investigational Site	Takamatsu	Kagawa
Japan	Pfizer Investigational Site	Toyota	Aichi
Japan	Pfizer Investigational Site	Yanagawa	Fukuoka
Japan	Pfizer Investigational Site	Zama	Kanagawa
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Wroclaw
Poland	Pfizer Investigational Site	Wroclaw
Slovakia	Pfizer Investigational Site	Bardejov
Slovakia	Pfizer Investigational Site	Bojnice
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Humenne
Slovakia	Pfizer Investigational Site	Kosice
Slovakia	Pfizer Investigational Site	Liptovsky Hradok
Slovakia	Pfizer Investigational Site	Namestovo
Slovakia	Pfizer Investigational Site	Poprad
Slovakia	Pfizer Investigational Site	Spisska Nova Ves
Slovakia	Pfizer Investigational Site	Sturovo
South Africa	Pfizer Investigational Site	Bloemfontein	Free State
South Africa	Pfizer Investigational Site	Cape Town
South Africa	Pfizer Investigational Site	Cape Town
South Africa	Pfizer Investigational Site	Durban
South Africa	Pfizer Investigational Site	Durban
South Africa	Pfizer Investigational Site	Gatesville	Western Cape
South Africa	Pfizer Investigational Site	Parow	Western Cape
South Africa	Pfizer Investigational Site	Pretoria
Spain	Pfizer Investigational Site	Merida	Badajoz
Spain	Pfizer Investigational Site	Petrer	Alicante
Spain	Pfizer Investigational Site	Pozuelo de Alarcon	Madrid
Spain	Pfizer Investigational Site	Salt	Girona
Sweden	Pfizer Investigational Site	Goteborg
Sweden	Pfizer Investigational Site	Linkoping
Sweden	Pfizer Investigational Site	Lund
Sweden	Pfizer Investigational Site	Malmo
Sweden	Pfizer Investigational Site	Skene
Taiwan	Pfizer Investigational Site	Taipei
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Brandon	Florida
United States	Pfizer Investigational Site	Charleston	South Carolina
United States	Pfizer Investigational Site	Charleston	South Carolina
United States	Pfizer Investigational Site	Charlotte	North Carolina
United States	Pfizer Investigational Site	Chiefland	Florida
United States	Pfizer Investigational Site	Chiefland	Florida
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Clearwater	Florida
United States	Pfizer Investigational Site	Clearwater	Florida
United States	Pfizer Investigational Site	Duluth	Georgia
United States	Pfizer Investigational Site	Edina	Minnesota
United States	Pfizer Investigational Site	Fort Mitchell	Kentucky
United States	Pfizer Investigational Site	Fridley	Minnesota
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Jasper	Alabama
United States	Pfizer Investigational Site	Kingsport	Tennessee
United States	Pfizer Investigational Site	Lexington	Kentucky
United States	Pfizer Investigational Site	Midvale	Utah
United States	Pfizer Investigational Site	Minneapolis	Minnesota
United States	Pfizer Investigational Site	Montclair	California
United States	Pfizer Investigational Site	New Port Richey	Florida
United States	Pfizer Investigational Site	Newark	Delaware
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Pawtucket	Rhode Island
United States	Pfizer Investigational Site	Pensacola	Florida
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Rochester	Minnesota
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Warwick	Rhode Island
United States	Pfizer Investigational Site	Waterbury	Connecticut
United States	Pfizer Investigational Site	Williston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Czech Republic,  Germany,  Hungary,  Japan,  Poland,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in trough (pre-treatment and pre-bronchodilator) Forced Expiratory Volume1 at Week 12.		Baseline, week 12	No
Secondary	Change from baseline in trough, pre-bronchodilator Forced Expiratory Volume1 at Weeks 2, 6, and 10		Baseline, week 2, 6, and 10	No
Secondary	Change from baseline in trough, pre-bronchodilator Forced Expiratory Volume6 at Weeks 2, 6, 10 and 12		Baseline, week 2, 6, 10 and 12	No
Secondary	Change from baseline in trough, pre-bronchodilator Forced Vital Capacity at Weeks 2, 6, 10 and 12		Baseline, week 2, 6, 10 and 12	No
Secondary	Change from baseline in trough, pre-bronchodilator Inspiratory Capacity at Weeks 2, 6, 10 and 12		Baseline, week 2, 6, 10 and 12	No
Secondary	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		Baseline, week 12	No
Secondary	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		Baseline, week 0, 12	No
Secondary	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		Baseline, week 0, week 12	No
Secondary	Change from baseline in Chronic Obstructive Pulmonary Disease symptoms (EXACT-PRO Daily Diary) over 12 weeks treatment.		Baseline, week 12	No
Secondary	Change from baseline in Chronic Respiratory Questionnaire - Self Administered Standard (CRQ-SAS) at Weeks 2, 6, 10 and 12		Baseline, week 2, 4, 6, 10 and 12	No
Secondary	Patient Global Impression of Change at Week 12		Baseline, week 12	No
Secondary	Change from baseline (Baseline Dyspnea Index) in dyspnea (Transition Dyspnea Index) at Weeks 2, 6, 10 and 12		Baseline, week 2, 4, 6, 10, and 12	No
Secondary	Clinician Global Impression of Change at Week 12		Baseline, week 12	No
Secondary	Rescue bronchodilator use (per daily diary) over 12 weeks of therapy		Baseline, week 12	No

External Links

•   To obtain contact information for a study center near you, click here.