Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 17.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Name: PF-03715455
Pharmaceutical Form: Capsule
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: PF-03715455
Other descriptive name: N-[3-tert-Butyl-1-(3-chloro-4-hydroxyphenyl)-1
Sponsors
Pfizer Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female subjects of non-childbearing potential and male subjects between the ages of 40 and 80 years, inclusive. Female subjects of non-childbearing potential must meet at least one of the following criteria: a. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle-stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women. b. Have undergone a documented hysterectomy and/or bilateral oophorectomy. c. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential. 2. Subjects with a diagnosis, for at least 6 months, of moderate to severe COPD (GOLD1) and who meet the criteria for Stage II-III disease: - Subjects must have a post-bronchodilator FEV1/FVC ratio 40 kg. 8. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 9. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Additional Inclusion Criteria for Sputum Sub-Study: 1. Subjects must be able to produce a sputum sample, at screening and randomization, which is sufficient to provide a differential count (50% neutrophils at screening. In the event that a subject meets all other Screening criteria but does not provide an evaluable sputum sample they may still be entered into the non-sputum study providing recruitment is still open. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Current evidence or history within the previous 6 months of any clinically 1. significant disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data 2. Subjects who have clinically significant (as deemed by investigator) abnormalities on physical examination, 12-lead ECG and vital signs (blood pressure and pulse) that would increase the risk to the patient or interfere with the interpretation of the safety or efficacy results. 3. A COPD exacerbation requiring treatment with oral steroids or hospitalization for the treatment of COPD within 3 months of Screening. 4. History of a lower respiratory tract infection or significant COPD disease instability during the 3 months preceding screening or during the time between screening and randomization. 5. History of an upper respiratory tract infection in the 4 weeks preceding screening or during the time between screening and randomization. 6. Use of inhaled corticosteroids within 3 months of Screening. 7. History or presence of respiratory failure, cor pulmonale or right ventricular failure. 8. Subjects with home oxygen therapy or long-term oxygen therapy. 9. Known history of adult asthma or other chronic respiratory disorders (eg, tuberculosis, bronchiectasis, pulmonary fibrosis, pneumoconiosis). 10. History of cancer (other than basal cell carcinoma or treated cervical carcinoma in situ) within the previous 5 years. 11. Symptoms, signs or laboratory findings (screening only) suggestive of an ongoing infective illness. 12. Participation in any clinical study with any investigational drug or marketed investigational biologic in the 4 months or 5 half-lives prior to the screening visit, whichever is longer. 13. ECG abnormalities at screening or randomisation including those listed below: a. Subjects with pre-randomization evidence of QTcF prolongation (defined as >450 ms for males and >470 ms for females) are not eligible for randomization. This assessment is based on a confirmed mean of the triplicate ECG recordings. b. Predominant heart rhythm other than normal sinus rhythm eg, atrial fibrillation, atrial flutter, supraventricular tachycardia. c. Atrioventricular (AV) block greater than first degree. d. Resting heart rate >100 or 1.5 x upper limit of normal (ULN). • Total bilirubin >1.5 x ULN. • Albumin 1.5 x ULN. • Hgb <10 g/dL, Hct <32%. • Absolute white blood count (WBC) count <3.0 x 109/L (<3000/mm3). • Neutrophil count <1.2 x 109/L (<1200/mm3). • Platelet count <120 x 109/L (<120,000/mm3). 16. Male subjects with partners who are currently pregnant; male subjects of child bearing potential (who are at risk for pregnancy with their female partners) and unwilling or unable to use a highly effective method of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect, at week 4, of orally inhaled PF-03715455 680 micrograms BID on trough FEV1 in subjects with moderate to severe COPD on a stable regimen of short or long acting bronchodilators.;Secondary Objective: - To determine the effect of orally inhaled PF-03715455 680 micrograms BID administered for 4 weeks, in sputum cell counts in a sub-study of subjects with moderate to severe COPD. - To determine the effect, averaged over 4 weeks, of orally inhaled PF-03715455 680 micrograms BID on trough FEV1 and forced vital capacity (FVC) in subjects with moderate to severe COPD on a stable regimen of short or long acting bronchodilators. - To explore the pharmacokinetics of PF-03715455 680 micrograms BID administered for 4 weeks in subjects with moderate to severe COPD.;Primary end point(s): Change from baseline in trough FEV1 at Week 4;Timepoint(s) of evaluation of this end point: Weeks 1, 3 and 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in sputum cell counts [Total neutrophil count and differential (%), total cell count, total macrophage count and differential (%)] over 4 weeks. - Change from baseline in trough FEV1 and FVC averaged over 4 weeks and at individual study visits. - Summary Pharmacokinetic data for PF-03715455. Safety Endpoints - 12 lead ECG, BP/pulse rate, safety laboratory tests and adverse events. Exploratory Endpoints - Change from baseline in sputum inflammatory markers may include but will not be limited to IL-6, IL-8, Neutrophil Elastase, eosinophil cationic protein (ECP), a2 macroglobulin, MCP-1, MIP-1ß and myeloperoxidase (MPO). - Change from baseline in sputum markers of pharmacology: Phospho p38 and phospho HSP27. - Change from baseline in high sensitivity C - reactive protein (hsCRP).;Timepoint(s) of evaluation of this end point: Week 4 | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed