A PHASE 2B, PARALLEL GROUP, PLACEBO AND ACTIVE COMPARATOR CONTROLLED STUDY TO INVESTIGATE THE SAFETY, TOLERATION AND EFFICACY OF 6-WEEK ONCE DAILY ADMINISTRATION OF INHALED PF-00610355 DRY POWDER IN PATIENTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2008-005249-51-EE
• Date of registration: 30/01/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Limited, Ramsgate Road, Sandwich, Kent UK
• Public title: A PHASE 2B, PARALLEL GROUP, PLACEBO AND ACTIVE COMPARATOR CONTROLLED STUDY TO INVESTIGATE THE SAFETY, TOLERATION AND EFFICACY OF 6-WEEK ONCE DAILY ADMINISTRATION OF INHALED PF-00610355 DRY POWDER IN PATIENTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE
• Scientific title: A PHASE 2B, PARALLEL GROUP, PLACEBO AND ACTIVE COMPARATOR CONTROLLED STUDY TO INVESTIGATE THE SAFETY, TOLERATION AND EFFICACY OF 6-WEEK ONCE DAILY ADMINISTRATION OF INHALED PF-00610355 DRY POWDER IN PATIENTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE
• Date of first enrolment: 27/02/2009
• Target sample size: 345
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005249-51
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Bulgaria, Czech Republic, Estonia, Germany, Hungary, Poland, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Male or female patients between, and including, the ages of 40 and 80 years. Females may be of either childbearing or non-child bearing potential. Females of non-child-bearing potential will be defined as:
• Females over the age of 60 years.
• Females who are 40-60 years of age who have been amenorrheic for at least 2 years and who have a serum FSH level >30 IU/L in the absence of hormone replacement therapy, or
• Females with a documented hysterectomy.
All females of childbearing potential may be included provided they are not pregnant (negative serum pregnancy test at screening) or nursing, and are practicing acceptable contraception methods:
• Abstinence.
• Tubal ligation.
• Physician documented placement of copper-containing intrauterine device (IUD).
• Diaphragm with spermicidal foam/gel/film/cream/pessary.
• Condom with spermicidal foam/gel/film/cream/pessary.
• Male partner who has had a vasectomy.
• Hormonal contraceptives (oral, injected, transdermal or implanted) in conjunction with a barrier method of contraception listed above.
• Hormonal contraceptives provided the subject remains on the treatment throughout the entire study and has been using hormonal contraceptives for an adequate period of time to ensure effectiveness (eg, 3 months for hormonal contraceptives).
3. Patients with a diagnosis, for at least 6 months, of moderate COPD (GOLD 2007) and who meet the criteria for Stage II disease:
Patients must have a post-bronchodilator FEV1/FVC ratio <0.7 and a post-bronchodilator FEV1 of 50-80% (inclusive) of the predicted value for age, height, race and sex using ECCS standards (Luxembourg 1993), when measured after a washout period of at least 6 hours during which no short-acting ?2-agonist was inhaled and at least 12 hours after the last use of long-acting 2-agonist.
To qualify for randomisation, these criteria must be met at screening and replicated during run-in visit.
4. Patients 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.
5. Patients must have stable disease for at least 1 month prior to screening. During the run-in phase patients must be able to manage disease symptoms adequately with short-acting bronchodilator only, with or without reliance on inhaled corticosteroids.
6. Body Mass Index (BMI) <45 kg/m2 and a total body weight >40 kg.
7. 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

Exclusion criteria:
1. More than 2 exacerbations of COPD requiring treatment with oral steroids in the preceding year or hospitalisation for the treatment of COPD within 3 months of screening or more than twice during the preceding year.
2. History of a lower respiratory tract infection or significant disease instability during the month preceding screening or during the time between screening and randomisation.
3. History or presence of respiratory failure, cor pulmonale or right ventricular failure.
4. Patients with home oxygen therapy (either PRN or long term oxygen therapy).
5. 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).
6. Known previous diagnosis of HIV infection (specific screening is not required), hepatitis B or C carrier status or chronic active hepatitis of any aetiology.
7. History within the previous year 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).
8. History within the previous 6 months of:
• An epileptic seizure.
• Poorly controlled Type 1 or Type 2 diabetes (as indicated by an HbA1c of 10% or greater).
• Acute hepatitis of any aetiology.
9. A major surgical operation within 1 month of screening.
10. Screening systolic blood pressure <90 mmHg.
11. Hypokalaemia (below LLN for reference laboratory).
12. ECG abnormalities at screening or randomisation, including those listed below. The investigator will decide whether ECG abnormalities other than those listed are clinically significant and should exclude the patient from enrolment:
• Predominant heart rhythm other than normal sinus rhythm eg, atrial fibrillation, atrial flutter, supraventricular tachycardia.
• Patients with pre-randomisation evidence of QTc prolongation (>450 msec) are not eligible for randomisation. This assessment is made by the investigator at the time of ECG collection.
• Atrioventricular (AV) block greater than first degree.
• Resting heart rate >100 or <50 bpm.
• Evidence of previous myocardial infarction or significant ischemic changes in the absence of clinical history consistent with these findings.
13. History or evidence, based upon a complete medical history, full physical examination, 12-lead resting ECG or clinical laboratory test results, of any other significant concomitant clinical disease that, in the opinion of the investigator, could interfere with the conduct, safety or interpretation of results of this study. Patients with certain chronic conditions such as hypertension, thyroid disease, Type 1 or Type 2 diabetes, hypercholesterolemia, gastroesophageal reflux, or depression may be included in the study as long as the conditions are well controlled and medications relating to the condition are stable and would not be predicted to compromise safety or interfere with the tests and interpretations of this study.
14. Liver function test abnormalities:
• Alanine amino transferase >3 x upper limit of normal (ULN).
• Aspartate amino transferase >3 x ULN.
• Alkaline phosphatase >1.5 x ULN.
• Total bilirubin >ULN.
15. Use of any investigational drug other than PF-00610355 during this study, or within 1 month prior to

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease
MedDRA version: 9.1 Level: LLT Classification code 10010952 Term: COPD

Intervention(s)

Product Code: PF-00610355
Pharmaceutical Form: Inhalation powder
CAS Number: 862541-45-5
Current Sponsor code: PF-00610355
Other descriptive name: (R)-N-[(4’-Hydroxybiphenyl-3-yl)methyl]-2-(3-{2-[2-hydroxy-2-(4-hydroxy-3-methanesulfonamidophenyl)e
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
CAS Number: 862541-45-5
Current Sponsor code: PF-00610355
Other descriptive name: (R)-N-[(4’-Hydroxybiphenyl-3-yl)methyl]-2-(3-{2-[2-hydroxy-2-(4-hydroxy-3-methanesulfonamidophenyl)e
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 300-
CAS Number: 862541-45-5
Current Sponsor code: PF-00610355
Other descriptive name: (R)-N-[(4’-Hydroxybiphenyl-3-yl)methyl]-2-(3-{2-[2-hydroxy-2-(4-hydroxy-3-methanesulfonamidophenyl)e
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Trade Name: Serevent Accuhaler™
Pharmaceutical Form: Inhalation powder
CAS Number: 89365-50-4
Current Sponsor code: Salmeterol
Other descriptive name: 2-(hydroxymethyl)-4-{1-hydroxy-2-[6-(4-phenylbutoxy) hexylamino]ethyl}phenol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Change from baseline in trough FEV1 at Week 6.

Secondary Objective: • To test all doses of PF-00610355 and salmeterol 50 µg for superior efficacy on peak
FEV1 vs placebo at Week 6.
• To characterise dose/response vs placebo at Week 6.
• To test all doses for superior efficacy on QOL and dyspnea vs placebo.
• To test all doses for superior efficacy vs placebo at Weeks 2 and 4.
• To investigate the dose response relationship of PF-00610355 vs ß2-mediated extra pulmonary effects in COPD patients, specifically: heart rate, blood pressure, QTc, arrhythmias and plasma potassium.

Main Objective: To test all doses (100, 300 and 600 µg) of PF-00610355 and salmeterol 50 µg for
superior efficacy on trough FEV1 vs placebo at Week 6.

Secondary ID(s)

A7881013

2008-005249-51-ES