Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Male or female subjects between, and including, the ages of 40 and 80 years. Female subjects of non-childbearing potential must meet at least one of the following criteria: 1. postmenopausal females, defined as: - Females over the age of 60 years. - Females between the ages of 45 to 60 who have been amenorrheic for at least 2 years PLUS have a serum FSH level within the laboratory’s reference range for postmenopausal females. 2. Females who have a documented hysterectomy and/or bilateral oophorectomy. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy and/or bilateral oophorectomy) will be considered to be of childbearing potential. 2. 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 10 actuations [100 µg/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. 6. Body Mass Index (BMI) 40 kg. 7. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal acceptable representative) has been informed of all pertinent aspects of the study).Subjects must be able to give informed, written consent prior to entering the study. 8. Subjects who are willing and able to comply with schedules visits, treatment plan, laboratory tests, and other study procedures.Subjects must be willing and able to comply with scheduled visit and all study-related procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 330 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 330
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 1. A COPD exacerbation requiring treatment with oral steroids or hospitalization for the treatment of COPD within 3 months of screening. 2. History of a lower respiratory tract infection or significant disease instability during the month preceding screening or during the time between screening and randomization. 3. History or presence of respiratory failure, cor pulmonale or right ventricular failure. 4. Subjects with home oxygen therapy (either PRN or long-term oxygen therapy). 5. Any clearly documented history of adult asthma or other chronic respiratory disorders (eg, bronchiectasis, pulmonary fibrosis, pneumoconiosis). 6. Known previous diagnosis of Hepatitis B or C or HIV infection (specific screening is not required). 7. History of cancer (other than cutaneous basal cell) in the previous 5 years. 8. Active or past history of GI hemorrhage of any etiology, peptic ulceration, erosive esophagitis, gastric outlet obstruction or inflammatory bowel disease. 9. Regular use of aspirin at a dose greater than 325 mg/day. 10. 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). 11. A family history of long QT syndrome. 12. Tuberculosis (TB): In order to be enrolled in the study, subjects will be screened for TB. Presence of any of the following means that the subject will be excluded: • Evidence or history of either untreated or inadequately treated latent or active tuberculosis infection. • A subject who is currently being treated for active TB infection. Note: a subject currently being treated for latent TB infection may be enrolled if criteria described in the protocol are met. • Positive reaction (=5 mm induration) of the PPD tuberculin skin test unless there has been documented vaccination with the bacilli Calmette-Guerin vaccine (BCG). • Chest X-ray (within last 3 months) with changes suggestive of active TB infection as determined by a qualified radiologist. 13. History within the previous 6 months of: • An epileptic seizure. • Poorly controlled Type 1 or Type 2 diabetes. • Acute hepatitis of any aetiology. 14. 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. 15. A major surgical operation within 1 month of screening. 16. ECG abnormalities at screening or randomization, including those listed below. The investigator will decide whether ECG abnormalities other than those listed are clinically significant and should exclude the subject from enrolment if abnormality is considered to be clinically significant: • Subjects with pre-randomization evidence of QTcF prolongation (defined as >450 ms) at screening or baseline (Week 0) are not eligible for randomization. This assessme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the dose response relationship of PH-797804 on change from baseline in trough (pre-treatment and pre-bronchodilator) FEV1 at Week 12 compared to placebo in COPD patients on a background of tiotropium.;Secondary Objective: • To determine the safety and toleration of PH-797804 in COPD patients on a background of tiotropium bromide. • To characterize the effect of all doses of PH-797804 on various spirometry endpoints: • Effect on change from baseline in trough (pre-treatment and pre-bronchodilator) FVC, IC and FEV6 at Week 12. • Time-course of effect over 12 weeks on change from baseline in trough FEV1, forced vital capacity (FVC), inspiratory capacity (IC) and FEV6. • Effect of single (Week 0) and 12 weeks multiple dosing on post-dose, pre-bronchodilator FEV1, FVC, IC and FEV6. • Effect of single (Week 0) and 12 weeks multiple dosing on change from baseline in post- bronchodilator FEV1, FVC, IC and FEV6. Please refer to the Protocol for the full list of objectives;Primary end point(s): Change from baseline in trough (pre-treatment and pre-bronchodilator) FEV1 at Week 12. ;Timepoint(s) of evaluation of this end point: Week 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Spirometry endpoints: • Change from baseline in trough, pre-bronchodilator FEV1 at Weeks 2, 6, and 10. • Change from baseline in trough, pre-bronchodilator FEV6, FVC and IC at Weeks 2, 6, 10 and 12. • Average change from baseline in trough, pre-bronchodilator FEV1, FEV6, FVC and IC over 12 weeks treatment. • Change from baseline in post-study drug, pre-bronchodilator FEV1, FEV6, FVC and IC at Weeks 0 and 12. • Change from baseline in post-study drug, post-bronchodilator FEV1, FEV6, FVC and IC at Weeks 0 and 12. Patient-reported endpoints: • Change from baseline in COPD symptoms (EXACT-PRO Daily Diary) over 12 weeks treatment. • Change from baseline in Chronic Respiratory Questionnaire - Self Administered Standard (CRQ-SAS) at Weeks 2, 6, 10 and 12. • Patient Global Impression of Change at Week 12. • Rescue bronchodilator use (per daily diary) over 12 weeks of therapy. Clinician (or other Site Staff)-rated endpoints: • Change from baseline (BDI) in dyspnea (TDI) at Weeks 2, 6, 10 and 12. • Clinician Global Impression of Change at Week 12. Other endpoints: • Population pharmacokinetics. Secondary Safety Endpoints • Adverse event reporting. • Laboratory safety data. • Change in ECG measurements post-study medication. • Change in pulse rate and blood pressure post-study medication.;Timepoint(s) of evaluation of this end point: Weeks 0, 2, 6, 10 and 12 | — |
Countries
Argentina, Bulgaria, Canada, Chile, Czech Republic, Germany, Hong Kong, Hungary, Japan, Poland, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc
Outcome results
None listed