A PHASE 2A, DOUBLE BLIND (3RD PARTY OPEN), 4 WAY CROSS-OVER, PLACEBO CONTROLLED STUDY TO INVESTIGATE THE PHARMACOKINETICS, SAFETY, TOLERATION AND EFFICACY OF SINGLE INHALED DOSES OF PF-00610355 IN MODERATE COPD PATIENTS
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 9.1Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease
- Registration Number
- EUCTR2008-001396-30-DE
- Lead Sponsor
- Pfizer Ltd, Ramsgate Road, Sandwich, Kent, UK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Male and/or female subjects between the ages of 40 and 80 years, inclusive with a diagnosis of moderate COPD (GOLD, 2007 update) and who meet the following criteria for GOLD stage II disease:
• Post-bronchodilator FEV1/ FVC ratio of <0.7, and a
• Post bronchodilator FEV1 of 50-80% (inclusive) of predicted for age, height, sex and race.
2. Body Mass Index (BMI) of less than 35 kg/m2; and a total body weight greater that 40 kg.
A BMI upper limit of 34.5 kg/m2 may be rounded down to 35.0 kg/m2 and will be acceptable for inclusion.
3. Subjects must have a smoking history of at least 10 pack-years (Formula for pack-years cigarettes = (average number of cigarettes/day ÷ 20) x years of smoking. Formula for pack-years tobacco = ounces per week x 2/7 x years of smoking) 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.
4. Subjects must have stable disease for at least 1 month prior to screening. Subjects must be able to manage their symptoms adequately with short-acting bronchodilators only. (salbutamol as needed, maximum of 8 actuations (100 µg/actuation) daily).
5. An informed consent document signed and dated by the subject.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Subjects presenting with any of the following will not be included in the study:
1. Subjects having more than 2 exacerbation requiring treatment with oral steroids or hospitalization for the treatment of COPD in the previous year.
2. Use of prescription or non-prescription drugs as follows:
• Subjects on medication having a significant effect on cardiac rate, conduction system (including QT interval) or myocardial function.
• Subjects on medication known to be cytochrome P-450 3A4 inhibitors (eg, antiinfective agents such as erythromycin, triazole anti-fungal agents, chloramphenicol and fluvoxamine) or cytochrome P-450 3A4 inducers (eg, phenobarbital and phenytoin).
• Subjects on inhaled corticosteroids.
3. Subjects on ß-blockers.
4. Subjects with uncontrolled hypertension. Stable hypertensive subjects are permitted but must remain on their anti-hypertensive medication through out the study and not change drug, regime or dose etc during the trial.
5. History of lower respiratory tract infection or significant disease instability during the month preceding screening or during the period between screening and randomization.
6. History or presence of respiratory failure, cor pulmonale or right ventricular failure.
7. Apart from COPD, any clearly documented history of adult asthma (onset of symptoms prior to the age of 40 years) or other chronic respiratory disorders (eg, bronchiectasis, pulmonary fibrosis, pneumoconiosis).
8. Abnormal 12-lead ECG including evidence of ischaemia, myocardial infarction,
arrhythmia or QTc >430 msec for women/QTc >450 msec for men. (If QTc exceeds
these limits, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the subject’s eligibility). Patients with familial long QT syndrome are also excluded.
9. A resting pulse rate >100 bpm or <50 bpm.
10. History within the previous year of: myocardial infarction, cardiac arrhythmia (eg, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia), cardiac insufficiency NYHA II-IV, left ventricular failure, unstable angina, coronary angioplasty, coronary artery bypass grafting (CABG) or cerebrovascular accident (including transient ischemic attacks).
11. Subjects with poorly controlled type I or type II diabetes, as indicated by an HbA1c of 10% or greater. Stable diabetics will be allowed.
12. Any of the following liver function test abnormalities:
• Alanine amino transferase >1.5 x upper limit of normal (ULN).
• Aspartate amino transferase >1.5 x ULN.
• Alkaline phosphatase >1.2 x ULN.
• Total bilirubin >1.5 x ULN.
13. A ferritin level 14. A potassium level 15. Positive HBsAg, HBcAB or anti-hepatitis C virus serology.
16. Use of any investigational drug within 3 months prior to dosing.
17. History of severe drug induced hypersensitivity (ie, anaphylaxis).
18. Known lactose intolerance or contraindicated for rescue/maintenance medication.
19. A positive urine drug screen.
20. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for men (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of spirits) within 6 months of screening.
21. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of nonhormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study me
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To characterize the single dose pharmacokinetics of inhaled PF-00610355 in COPD<br>patients.<br>• To evaluate the safety & toleration of single inhaled doses of PF-00610355 in COPD<br>patients.;Secondary Objective: • To investigate the efficacy of a single inhaled dose of PF-00610355 in COPD patients.<br>• To investigate the exposure/response relationship of PF-00610355 versus ß2-mediated extra pulmonary effects in COPD patients in conjunction with prior knowledge from HV and asthmatic population, specifically: heart rate, blood pressure, QTc, arrhythmias, plasma potassium and blood glucose.;Primary end point(s): 1.PF-00610355 PK: AUCinf, AUClast, Tmax, Cmax, T½.<br>2. Systemic safety: Maximal and weighted mean (AUEC) change from baseline over 24 hr post dose in heart rate (pulse rate), plasma potassium, blood glucose, blood pressure and QTc.
- Secondary Outcome Measures
Name Time Method