| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010952 |
| E.1.2 | Term | COPD |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To test all doses (100, 300 and 600 µg QD) of PF-00610355 and salmeterol 50 µg (BID) for superior efficacy on trough FEV1 vs placebo at Week 6. |
|
| E.2.2 | Secondary objectives of the trial |
To test all doses of PF-00610355 and salmeterol 50 µg for superior efficacy on peak FEV1 vs placebo at Day 1 and Week 6.
To characterise dose/response vs placebo at Week 6.
To test all doses of PF-00610355 and salmeterol for superior efficacy on QOL, COPD
symptoms, and dyspnea and rescue medication use vs placebo.
To test all doses and salmeterol for superior efficacy vs placebo at Weeks 2 and 4.
To investigate the dose response relationship of PF-00610355 vs β2-mediated extra
pulmonary effects in COPD patients, specifically: heart rate, blood pressure, QTc,
arrhythmias and plasma potassium. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. 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-childbearing 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 in 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-bronchodilator1 FEV1/FVC ratio <0.7 and a postbronchodilator 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 β2-agonist was inhaled, at least 24 hours after the last use of long-acting βagonist, 48 hours after the last use of LAMA and 8 hours after the last use of SAMA.
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 2 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 runin 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. |
|
| E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
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.
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. Participation in other studies within 1 month before the current study begins and/or during study participation.
16. Use of any of the prohibited medications within the indicated time frame prior to the start of screening
17. History of severe drug induced hypersensitivity (ie, anaphylaxis).
18. Known lactose intolerance or contra-indication for rescue/maintenance medication.
19. Pregnant or nursing females, or females intending to become pregnant during the course of the study.
20. Donation of or intent to donate blood, or blood components during the study or within 1 month prior or after completion of the study.
21. Evidence of alcohol or drug abuse or dependency (specific screening is not required).
22. Inability to inhale correctly from multiple dose inhaler devices (MDI, CRC-749 DPI) for any reason.
23. Inability to comprehend, or unwillingness to follow, the study requirements including attendance at out-patient clinic visits and participation in laboratory testing as called for by the protocol.
24. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in trough FEV1 at Week 6. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| See protocol, section 13 " DEFINITION OF END OF TRIAL" |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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