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

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

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)

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: PH-797804; Drug: PH-797804; Drug: PH-797804; Drug: PH-797804; Drug: PH-797804; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1426
    • Pfizer Investigational Site
• Bulgaria
  • Ruse, Bulgaria, 7002
    • Pfizer Investigational Site
  • Sevlievo, Bulgaria, 5400
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1431
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1000
    • Pfizer Investigational Site
  • Stara Zagora, Bulgaria, 6003
    • Pfizer Investigational Site
  • Troyan, Bulgaria, 5600
    • Pfizer Investigational Site
  • Veliko Tarnovo, Bulgaria, 5000
    • Pfizer Investigational Site
• Canada
  • Quebec, Canada, G3K 2P8
    • Pfizer Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2K 3S8
      • Pfizer Investigational Site
  • Ontario
    • Toronto, Ontario, Canada, M6H 3M2
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5T 3A9
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4N 3C5
      • Pfizer Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Pfizer Investigational Site
    • St-Romuald, Quebec, Canada, G6W 5M6
      • Pfizer Investigational Site
• Czech Republic
  • Karlovy Vary, Czech Republic, 36009
    • Pfizer Investigational Site
  • Liberec, Czech Republic, 460 01
    • Pfizer Investigational Site
  • Melnik, Czech Republic, 27601
    • Pfizer Investigational Site
  • Praha 10, Czech Republic, 108 00
    • Pfizer Investigational Site
  • Praha 5, Czech Republic, 153 00
    • Pfizer Investigational Site
  • Rokycany, Czech Republic, 337 22
    • Pfizer Investigational Site
  • Teplice, Czech Republic, 41501
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Pfizer Investigational Site
  • Berlin, Germany, 13125
    • Pfizer Investigational Site
  • Dresden, Germany, 01069
    • Pfizer Investigational Site
  • Gelnhausen, Germany, 63571
    • Pfizer Investigational Site
  • Grosshansdorf, Germany, 22927
    • Pfizer Investigational Site
  • Hamburg, Germany, 20253
    • Pfizer Investigational Site
  • Hamburg, Germany, 20354
    • Pfizer Investigational Site
  • Hannover, Germany, 30159
    • Pfizer Investigational Site
  • Kassel, Germany, 34121
    • Pfizer Investigational Site
  • Luebeck, Germany, 23552
    • Pfizer Investigational Site
  • Schwerin, Germany, 19055
    • Pfizer Investigational Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Pfizer Investigational Site
  • Budaors, Hungary, 2040
    • Pfizer Investigational Site
  • Budapest, Hungary, 1122
    • Pfizer Investigational Site
  • Debrecen, Hungary, 4032
    • Pfizer Investigational Site
  • Szeged, Hungary, 6722
    • Pfizer Investigational Site
  • Szombathely, Hungary, 9700
    • Pfizer Investigational Site
  • Torokbalint, Hungary, 2045
    • Pfizer Investigational Site
• Japan
  • Fukuoka, Japan
    • Pfizer Investigational Site
  • Kumamoto, Japan
    • Pfizer Investigational Site
  • Osaka, Japan
    • Pfizer Investigational Site
  • Aichi
    • Nagoya, Aichi, Japan
      • Pfizer Investigational Site
    • Toyota, Aichi, Japan
      • Pfizer Investigational Site
  • Aichi-ken
    • Seto-shi, Aichi-ken, Japan
      • Pfizer Investigational Site
  • Chiba
    • Noda, Chiba, Japan
      • Pfizer Investigational Site
  • Fukuoka
    • Yanagawa, Fukuoka, Japan
      • Pfizer Investigational Site
  • Ishikawa
    • Kanazawa, Ishikawa, Japan
      • Pfizer Investigational Site
  • Kagawa
    • Takamatsu, Kagawa, Japan
      • Pfizer Investigational Site
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan
      • Pfizer Investigational Site
    • Zama, Kanagawa, Japan
      • Pfizer Investigational Site
  • Oita
    • Saiki, Oita, Japan
      • Pfizer Investigational Site
  • Tokyo
    • Meguro-ku, Tokyo, Japan
      • Pfizer Investigational Site
    • Setagaya, Tokyo, Japan
      • Pfizer Investigational Site
• Poland
  • Warszawa, Poland, 04-141
    • Pfizer Investigational Site
  • Wroclaw, Poland, 53-301
    • Pfizer Investigational Site
  • Wroclaw, Poland, 54-239
    • Pfizer Investigational Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Pfizer Investigational Site
  • Bojnice, Slovakia, 972 01
    • Pfizer Investigational Site
  • Bratislava, Slovakia, 826 06
    • Pfizer Investigational Site
  • Bratislava, Slovakia, 841 04
    • Pfizer Investigational Site
  • Humenne, Slovakia, 066 01
    • Pfizer Investigational Site
  • Kosice, Slovakia, 040 01
    • Pfizer Investigational Site
  • Liptovsky Hradok, Slovakia, 033 01
    • Pfizer Investigational Site
  • Namestovo, Slovakia, 029 01
    • Pfizer Investigational Site
  • Poprad, Slovakia, 058 01
    • Pfizer Investigational Site
  • Spisska Nova Ves, Slovakia, 052 01
    • Pfizer Investigational Site
  • Sturovo, Slovakia, 943 01
    • Pfizer Investigational Site
• South Africa
  • Cape Town, South Africa, 7500
    • Pfizer Investigational Site
  • Cape Town, South Africa, 7530
    • Pfizer Investigational Site
  • Durban, South Africa, 4001
    • Pfizer Investigational Site
  • Durban, South Africa, 4126
    • Pfizer Investigational Site
  • Pretoria, South Africa, 0181
    • Pfizer Investigational Site
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Pfizer Investigational Site
  • Western Cape
    • Gatesville, Western Cape, South Africa, 7764
      • Pfizer Investigational Site
    • Parow, Western Cape, South Africa, 7505
      • Pfizer Investigational Site
• Spain
  • Alicante
    • Petrer, Alicante, Spain, 03610
      • Pfizer Investigational Site
  • Badajoz
    • Merida, Badajoz, Spain, 06800
      • Pfizer Investigational Site
  • Girona
    • Salt, Girona, Spain, 17190
      • Pfizer Investigational Site
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Pfizer Investigational Site
• Sweden
  • Goteborg, Sweden, 412 63
    • Pfizer Investigational Site
  • Linkoping, Sweden, 58216
    • Pfizer Investigational Site
  • Lund, Sweden, 22185
    • Pfizer Investigational Site
  • Malmo, Sweden, 211 52
    • Pfizer Investigational Site
  • Skene, Sweden, 511 62
    • Pfizer Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35233
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35294
      • Pfizer Investigational Site
    • Jasper, Alabama, United States, 35501
      • Pfizer Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pfizer Investigational Site
  • California
    • Montclair, California, United States, 91763
      • Pfizer Investigational Site
    • San Diego, California, United States, 92120
      • Pfizer Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Pfizer Investigational Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Pfizer Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Pfizer Investigational Site
    • Chiefland, Florida, United States, 32626
      • Pfizer Investigational Site
    • Chiefland, Florida, United States, 32226
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33756
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33765
      • Pfizer Investigational Site
    • New Port Richey, Florida, United States, 34653
      • Pfizer Investigational Site
    • Pensacola, Florida, United States, 32504
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33603
      • Pfizer Investigational Site
    • Williston, Florida, United States, 32696
      • Pfizer Investigational Site
  • Georgia
    • Duluth, Georgia, United States, 30096
      • Pfizer Investigational Site
  • Kentucky
    • Fort Mitchell, Kentucky, United States, 41017
      • Pfizer Investigational Site
    • Lexington, Kentucky, United States, 40504
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Pfizer Investigational Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Pfizer Investigational Site
    • Fridley, Minnesota, United States, 55432
      • Pfizer Investigational Site
    • Minneapolis, Minnesota, United States, 55407
      • Pfizer Investigational Site
    • Rochester, Minnesota, United States, 55905
      • Pfizer Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Pfizer Investigational Site
    • Albuquerque, New Mexico, United States, 87108
      • Pfizer Investigational Site
    • Albuquerque, New Mexico, United States, 87110
      • Pfizer Investigational Site
  • New York
    • Rochester, New York, United States, 14618
      • Pfizer Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45242
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45245
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Pfizer Investigational Site
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Pfizer Investigational Site
    • Warwick, Rhode Island, United States, 02886
      • Pfizer Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Pfizer Investigational Site
    • Charleston, South Carolina, United States, 29407
      • Pfizer Investigational Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Pfizer Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78212
      • Pfizer Investigational Site
  • Utah
    • Midvale, Utah, United States, 84047
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Placebo	Drug: Placebo; Placebo oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
EXPERIMENTAL: PH-787904 (arm1)	Drug: PH-797804; 0.25 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 1 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 3 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 6 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 10 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
EXPERIMENTAL: PH-787904 (arm2)	Drug: PH-797804; 0.25 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 1 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 3 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 6 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 10 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
EXPERIMENTAL: PH-787904 (arm3)	Drug: PH-797804; 0.25 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 1 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 3 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 6 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 10 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
EXPERIMENTAL: PH-787904 (arm4)	Drug: PH-797804; 0.25 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 1 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 3 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 6 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 10 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks
EXPERIMENTAL: PH-787904 (arm5)	Drug: PH-797804; 0.25 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 1 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 3 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 6 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks; Drug: PH-797804; 10 mg oral tablet plus tiotropium bromide 18 microgram once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in trough (pre-treatment and pre-bronchodilator) Forced Expiratory Volume1 at Week 12.	Baseline, week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in trough, pre-bronchodilator Forced Expiratory Volume1 at Weeks 2, 6, and 10	Baseline, week 2, 6, and 10
Change from baseline in trough, pre-bronchodilator Forced Expiratory Volume6 at Weeks 2, 6, 10 and 12	Baseline, week 2, 6, 10 and 12
Change from baseline in trough, pre-bronchodilator Forced Vital Capacity at Weeks 2, 6, 10 and 12	Baseline, week 2, 6, 10 and 12
Change from baseline in trough, pre-bronchodilator Inspiratory Capacity at Weeks 2, 6, 10 and 12	Baseline, week 2, 6, 10 and 12
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
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
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
Change from baseline in Chronic Obstructive Pulmonary Disease symptoms (EXACT-PRO Daily Diary) over 12 weeks treatment.	Baseline, week 12
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
Patient Global Impression of Change at Week 12	Baseline, week 12
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
Clinician Global Impression of Change at Week 12	Baseline, week 12
Rescue bronchodilator use (per daily diary) over 12 weeks of therapy	Baseline, week 12

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: February 28, 2012
• First Submitted That Met QC Criteria: March 2, 2012
• First Posted (ESTIMATE): March 5, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 27, 2014
• Last Update Submitted That Met QC Criteria: October 15, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: A6631033