| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Pulmonary obstructive Disease (COPD) |
|
| 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 |
| The primary objective of this study is to evaluate the dose response, efficacy and safety of five dosage regimens of LABA GW642444M with lactose and magnesium stearate (3.0mcg, 6.25mcg, 12.5mcg, 25mcg and 50mcg) in subjects with COPD to inform the selection of doses for use in further clinical studies in this population and other COPD populations. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives in this study are to evaluate the population pharmacokinetic profile of GW642444M with lactose and magnesium stearate in COPD patients and to collect blood samples for a pharmacogenetic study. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| The primary endpoint for this study is the change from baseline in clinic visit trough (prebronchodilator and pre-dose) FEV1 at the end of the 28-day treatment period. The trough FEV1 will be defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. |
|
| E.3 | Principal inclusion criteria |
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Informed Consent: Subjects who give their signed written informed consent to
participate.
2. Gender: Male or females who are 40 - 80 years of age at Visit 1.
A female is eligible to enter and participate in the study if she is of:
Non-child bearing potential (i.e. physiologically incapable of becoming pregnant,
including any female who is post-menopausal); or
Child bearing potential, has a negative pregnancy test at screening, and agrees to
one of the following acceptable contraceptive methods used consistently and
correctly (i.e. in accordance with the approved product label and the instructions of
the physician for the duration of the study – screening to follow-up contact):
• Complete abstinence from intercourse from screening until 2 weeks after the
follow-up contact; or
• Male partner is sterile (vasectomy with documentation of azoospermia) prior to
female subject entry into the study, and this male partner is the sole partner for
that subject; or
• Implants of levonorgestral inserted for at least 1 month prior to the study
medication administration but not beyond the third successive year following
insertion; or
• Injectable progestogen administered for at least 1 month prior to study
medication administration and administered for 1 month following study
completion; or
• Oral contraceptive (combined or progestogen only) administered for at least one
monthly cycle prior to study medication administration; or
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault
caps) plus spermicidal agent (foam/gel/film/cream/suppository); or
• An intrauterine device (IUD), inserted by a qualified physician, with published
data showing that the highest expected failure rate is less than 1% per year; or
• Estrogenic vaginal ring; or
• Percutaneous contraceptive patches
3. COPD Diagnosis: Subjects with an established clinical history of COPD in
accordance with the following definition by the American Thoracic
Society/European Respiratory Society [Celli, 2004]:
COPD is a preventable and treatable disease characterised by airflow limitation that
is not fully reversible. The airflow limitation is usually progressive and is associated
with an abnormal inflammatory response of the lungs to noxious particles or gases,
primarily caused by cigarette smoking. Although COPD affects the lungs, it also
produces significant systemic consequences.
4. Tobacco Use: Must have current or prior history of at least 10 pack-years of
cigarette smoking. [number of pack years = (number of cigarettes per day / 20) x
number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
5. Severity of Disease:
• Subjects with a measured post-salbutamol FEV1/FVC ratio of ≤0.70 at Visit 1
(Screening).
• Subjects with a measured post-salbutamol FEV1 ≥35 and ≤70% of predicted
normal values calculated using NHANES III reference equations at Visit 1
(Screening). |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Pregnancy: Women who are pregnant or lactating.
2. Asthma: Subjects with a primary diagnosis of asthma. (Subjects with a prior
history of asthma are eligible if COPD is currently their primary diagnosis)
3. α1-antitrypsin deficiency: Subjects with α1-antitrypsin deficiency as the underlying cause of COPD.
4. Other Respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung
disease or other active pulmonary disease.
5. Lung Resection: Subjects with lung volume reduction surgery within the previous
12 months.
6. Chest X-ray: Chest X-ray (or CT scan) reveals evidence of clinically significant
abnormalities not believed to be due to the presence of COPD. Please view protocol for further information.
7. Hospitalization: Subjects who are hospitalized due to poorly controlled COPD
within 12 weeks of the screening visit.
8. Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the
occurrence of any of the following in the 6 weeks prior to Visit 1:
• acute worsening of COPD that is managed by subject with corticosteroids or
antibiotics, or
• acute worsening of COPD that requires treatment prescribed by a physician
9. Other Diseases/Abnormalities: Subjects with clinically significant cardiovascular
neurological, psychiatric, renal, immunological, endocrine (including uncontrolled
diabetes or thyroid disease) or hematological abnormalities that are uncontrolled.
10. Lower Respiratory Tract Infection: Subjects with lower respiratory tract
infections which required the use of antibiotics within 6 weeks prior to visit 1.
11. 12-Lead ECG: An abnormal and clinically significant 12-lead electrocardiogram
(ECG) that results in an active medical problem. For the purposes of this study, an
abnormal ECG is defined as a 12-lead tracing which is interpreted with (but not
limited to) any of the following: Please view protocol for further information.
• A mean QTc(B) value at screening >450msec, or uncorrected QT>600msec or an
ECG that is not suitable for QT measurements (e.g. poorly defined termination
of the T wave) Please view protocol for further information.
12. Hypertension: Subjects with clinically significant hypertension that is uncontrolled.
13. Hepatitis: Subjects with a positive Hepatitis B surface antigen or positive hepatitis C antibody pre-study or at Screening.
14. Cancer: Subjects with carcinoma that has not been in complete remission for at
least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal
cell carcinoma would not be excluded if the subject was considered cured in less than 5 years since diagnosis.
15. Drug allergy: Subjects with a history of hypersensitivity to any beta-agonist or any component of the MDI and/or nebule or sensitivity to any of the constituents of the dry powder product (magnesium stearate or lactose). In addition patients with a
history of severe milk protein allergy would also be excluded.
16. Drug abuse: Subjects with a known or suspected history of alcohol or drug abuse
within the last 2 years.
17. Medication prior to spirometry: Subjects who are medically unable to withhold
their salbutamol for the 6 hour period required prior to spirometry testing at each
study visit would be ineligible for the study.
18. Additional Medications: The following medications are not permitted during this
study and must not have been taken for the indicated times prior to Visit 1 (Please view protocol for Prohibited Medications):
19. Other Medications: Subjects receiving treatment with tricyclic antidepressants,
MAOs, beta-adrenergic antagonists, anticonvulsants (barbiturates, hydantoins, and
carbamazepine) or phenothiazines would be ineligible for the study.
20. Oxygen: Subjects receiving long-term-oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use is not
exclusionary.
21. Sleep apnea: Subjects with clinically significant sleep apnea that is uncontrolled.
22. Pulmonary Rehabilitation: Please see protocol for further information.
23. Non-compliance: Subjects unable to comply with study procedures.
24. Affiliation with investigator site: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or immediate family members
of the aforementioned are excluded from participation in this study.
25. Questionable validity of Consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation, substance abuse, (including drug and
alcohol), or other conditions, which will limit the validity of informed consent to
participate in the study.
26. Prior use of Study Medication: Subjects who have received the investigational
drug GW642444 in previous studies.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint for this study is the change from baseline in clinic visit trough (prebronchodilator and pre-dose) FEV1 at the end of the 28-day treatment period. The trough FEV1 will be defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| 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 | No |
| 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
| |
| 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 | 4 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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