A PHASE II, RANDOMIZED, DOUBLE-BLIND, 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 SALMETEROL XINAFOATE/FLUTICASONE PROPIONATE COMBINATION

• Register: EUCTR
• Last refreshed on: 17 June 2013
• Main ID: EUCTR2010-024219-15-SE
• Date of registration: 14/03/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
• Public title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, 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 SALMETEROL XINAFOATE/FLUTICASONE PROPIONATE COMBINATION
• Scientific title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, 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 SALMETEROL XINAFOATE/FLUTICASONE PROPIONATE COMBINATION
• Date of first enrolment: 16/06/2011
• Target sample size: 328
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024219-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, Hungary, Poland, Slovakia, Sweden, United Kingdom

Key inclusion & exclusion 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 enrolment into the trial:
1. Male or female subjects between, and including, the ages of 40 and 80 years. Females must be of non-childbearing potential. Females of non-child-bearing potential will be defined as:
• Females who have been amenorrheic for at least 2 years and have a serum FSH level >30 IU/L in the absence of hormone replacement therapy or have a documented hysterectomy and/or bilateral oophrectomy.
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 < 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. To qualify for randomization, these criteria must be met at Screening and replicated during run-in phase (see randomization criteria for details).
3. 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.
*Formula for pack-years:
cigarettes = (average number of cigarettes/day ÷ 20) x years of smoking.
tobacco = ounces per week x 2/7 x years of smoking.
4. Subjects treated with LABA/ICS combination at a stable dose(s) approved for COPD for at least 1 month prior to screening.
5. 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 SFC +/-salbutamol (albuterol) rescue medication (subjects should not use >10 actuations [100 µg/actuations] daily for more than 2 consecutive days), without reliance on other therapies including oral or additional inhaled corticosteroids, other long-acting bronchodilators, nebulizer therapy, theophylline or regular oxygen.
6. Body Mass Index (BMI) <35 kg/m2 and a total body weight >40 kg.
7. Subjects must be able to give informed, written consent prior to entering the study.
8. 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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, [LTOT]).
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 2 years 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 without treatment and/or positive tuberculin reaction to PPD (Purified Protein Deriviative) without known (documented) vaccination with the bacilli Calmette-Guerin vaccine (BCG).
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 (See Appendix 3 for details).
• 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 at screening or baseline Week 0 (defined as >450 ms) 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.
17. History or evidence, based upon a complete medical history, full ph

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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 13.1 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: Not Applicable
Product Code: PH-797804
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
Current Sponsor code: PH-797804
Other descriptive name: Not Applicable
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Comparison between treatments in the change from baseline in pre-bronchodilator, trough (prior to administration of study medication and other back ground medications) forced expiratory volume in one second (FEV1) at Week 12.

Main Objective: To evaluate the efficacy and safety/tolerability of 12 weeks administration of PH-797804 in adults with moderate to severe COPD (GOLD stage II/III) on a background of salmeterol xinafoate/fluticasone propionate combination.

Secondary Objective: None

Secondary ID(s)

A6631029