| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease |
|
| MedDRA Classification |
| 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, dose interval,
efficacy, and safety of GSK961081 by studying three QD doses (100mcg, 400mcg and
800mcg) and three BID doses (100mcg, 200mcg and 400mcg) and salmeterol (50mcg) BID compared with placebo delivered by DISKUS in subjects with COPD. |
|
| E.2.2 | Secondary objectives of the trial |
The study will also evaluate the population PK, systemic PK-PD, dose-response and
dose-time-response FEV1 profile of GSK961081, and collect blood samples for a
pharmacogenetic study in this COPD patient population. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Outpatient subjects
2. Subjects who give their signed and dated informed consent to participate.
3. ≥ 40 years of age, inclusive, at Visit 1.
4. Gender: Male or females
Females are 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
• Condom and 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
5. 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 characterized 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.
6. Current or previous cigarette smokers with a history of ≥ 10 packyears
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 subjects who have stopped smoking at least 6 months prior to Visit 1.
7. Subjects with the following liver function test values:
• aspartate transaminase (AST) or alanine transaminase (ALT) <2x Upper Limit
Normal (ULN).
• alkaline phosphatase (alk phos), and bilirubin <1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
8.
• Subjects with a measured post-salbutamol FEV1/FVC ratio of < 0.70 at Visit 1
(Screening).
• Subjects with a measured post-salbutamol FEV1 ≥30 and ≤70% of predicted
normal values calculated using NHANES III [Hankinson, 1999] reference
equations at Visit 1 (Screening). |
|
| E.4 | Principal exclusion criteria |
1. Women: pregnant or lactating or are planning to become pregnant during the study.
2. Subjects with a current diagnosis of asthma. (Subjects with a prior history
of asthma are eligible if they have a current diagnosis of COPD).
3. Known respiratory disorders other than COPD including but not limited to α-1 antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease. Allergic rhinitis is not exclusionary.
4. Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy).
5. Chest X- ray (or CT scan) which reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Chest Xray must be taken if a chest X-ray or CT scan is not available within 6 months prior
to Visit 1. For subjects in Germany, if a chest X-ray (or CT scan) is not available in
the 6 months prior to Visit 1 the subject will not be eligible for the study.
6. Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1.
7. Hospitalisation for COPD or pneumonia within 12 weeks prior to Visit 1.
8. Use of antibiotics for a lower respiratory tract infection within 6 weeks prior to Visit 1.
9. Significant diseases (including uncontrolled hypertension, diabetes and thyroid disease) that would put the safety of the subject at risk through study participation, or which would affect study analyses if the diseases/condition exacerbated during the study. Symptomatic (or a documented history of) laryngopharyngeal reflux (LPR), extraesophageal reflux (EER) or posterior laryngitis. Subjects with a previous history of laryngopharyngeal ulcerations and erosions.
10. BMI value of >35kg/ m2
11. Presence of a paced rhythm on a 12-lead ECG which causes the underlying rhythm and ECG to be obscured
12. An abnormal and clinically significant 12-lead ECG. Refer to page 21 of the protocol.
13. A positive Hepatitis B surface antigen or positive hepatitis C antibody at
Visit 1 (if hepatitis C antibody is positive, a hepatitis C RIBA immunoblot assay
should be reflexively performed on the same sample to confirm the result).
14. Current or chronic history of liver disease, known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
15. Current malignancy or previous history of cancer in remission for < 5 years prior to Visit 1 (localised basal cell or squamous cell carcinoma of the skin that has been resected is not exclusionary.) Current or previous history of throat cancer.
16. History of hypersensitivity or allergy to any beta adrenergic receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor antagonist, or lactose/milk protein, which contraindicates study participation.
17. Medical diagnosis of narrow- angle glaucoma, prostatic hypertrophy or bladder neck obstruction that would prevent use of an inhaled anticholinergic.
18. Medically unable to withhold their salbutamol for the 4 H period required prior to spirometry testing at each study visit.
19. Additional medications (refer to page 23 of the protocol)
20. Use of long term oxygen therapy or supplemental oxygen required for greater than 12 hours a day. Oxygen PRN use is not exclusionary.
21. Regular (q.i.d or greater) use of short acting bronchodilators, including nebulized therapy
22. Use of continuous positive airway pressure (CPAP), nocturnal positive pressure or non invasive positive pressure ventilation (NIPPV), including for sleep apnea.
23. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
24. Is an investigator, sub investigator, study coordinator, employee of a participating investigator or study site or immediate family members of the aforementioned that is involved in this study.
25. History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse or suspected substance abuse in the 2 years prior to Visit 1 (including drug and alcohol), or other conditions which will limit the validity of the informed consent to participate in the study.
26. Use of GSK961081 in previous studies. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint:
The primary endpoint for this study is the change from baseline in AM trough FEV1 on
Day 29 (defined as the mean of the values recorded 11 H and 12 H after the PM dose 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 | Yes |
| 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 | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 30 |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned days | 7 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 7 |
Print
