| 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 |
To assess the safety and tolerability of GW856553 administered orally for 14 days in
patients with COPD. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the systemic anti-inflammatory activity of GW856553 administered orally
for 14 days in patients with COPD as determined by changes in systemic biomarkers
(whole blood).
To assess the pharmacokinetics of GW856553 and GSK198602 (a known
metabolite) in patients with COPD. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
A patient will be eligible for inclusion in this study only if all of the following criteria apply:
1. Males and females aged between 40 and 75 years of age (inclusive).
To be eligible, females patients must have a negative pregnancy test (i.e. serum beta hCG test) and be of:
a) non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status will be confirmed by serum FSH and oestradiol concentrations at screening. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation.
OR
b. child-bearing potential and agrees to commit to one of the protocol-approved methods of contraception, when used consistently and in accordance with both the product label and the instructions of a physician, as indicated below:
• oral contraceptive (combined or progestin only), and the same oral contraceptive regimen has been used for at least two months prior to study drug administration, and the same method continues throughout the study and through the follow-up phase of the study.
• progesterone implanted rods (Norplant ) inserted for at least two month prior to the study drug administration (but not beyond the third successive year following insertion) , and is continued throughout the study and through the follow-up phase of the study.
• an IUD, inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion) Acceptable IUDs: TCu-380A (Paragard), TCU-380 Slimline (Gyne T Slimline), TCu-220C, MULTILOAD-250 (MLCu-250) and 375, NOVA T and CUNOVAT (Novagard), Levonorgesterol (LNG-20) Intra-uterine System (Mirena/Levonova), and FlexiGard 330/CuFix PP330 (Gynefix). The device must be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and through the follow-up phase of the study.
• Injectable medroxyprogesterone acetate (e.g., Depo-Provera) and is on a stable dose for 2 months prior to Screen, throughout the study and through the follow-up phase of the study.
• complete abstinence from intercourse from at least two weeks prior to Screen, throughout the treatment phase, and the follow-up phase.
• double barrier method if comprised of a spermicide with either a condom or diaphragm from at least two weeks prior to Screen, throughout the treatment phase, and the follow-up phase.
2. An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society: [American Thoracic Society/ European Respiratory Society, 2004].
3. Body weight greater than 50 kg (110 lbs) for men and greater than 45 kg (99lbs) for women.
4. Normal Posterior-anterior chest radiograph: A chest X-ray must be obtained prior to Visit 2, unless the patient has had a chest X-ray performed within 12 months prior to Visit 1 and the film is available to the investigator. If the X-ray reveals any chest abnormality other than features of COPD, that the investigator and medical monitor consider may interfere with study procedures, the patient must be excluded from the study.
5. Patients with a cigarette smoking history of greater than 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or the equivalent). Both current and former smokers are eligible to be enrolled. A former smoker is defined as a patient who has not smoked for ≥ 6 months at Visit 1.
6. Patients with a post-bronchodilator FEV1 to FVC ratio (FEV1: FVC) < 0.7 at Visit 1. Patients will be assessed 30 (± 5) minutes after receiving salbutamol 400µg.
7. Patients with a post-bronchodilator FEV1 ≥ 40% and < 80% of predicted normal for height, age and sex at Visit 1. Patients will be assessed 30 (± 5) minutes after receiving salbutamol 400µg.
|
|
| E.4 | Principal exclusion criteria |
A patient will not be eligible for inclusion in this study if any of the following criteria apply:
1. Patients in whom treatment for COPD with Salbutamol and/or ipratropium only for the period of the study is clinically inappropriate. See section 9 of protocol for details of permitted and prohibited medications.
2. Patients who have required hospitalisation or treatment with oral corticosteroids and/or antibiotic therapy for acute worsening of COPD or lower respiratory tract infection in the 6 weeks prior to Screening.
3. Patients with a history of any type of malignancy with the exception of successfully treated squamous cell cancer of the skin.
4. Patients with a current diagnosis of asthma, active tuberculosis, sarcoidosis or clinically overt bronchiectasis. Patients who have undergone recent surgery including lung volume reduction surgery or have conditions that prevent them from performing spirometry.
5. Patients with a total bilirubin concentration above the upper limit of normal at Screening will be excluded. History of increased liver function tests (ALT, AST) above upper limit of normal in the past 6 months and/or liver function tests (bilirubin, ALT, AST) above upper limit of normal at Screening (Visit 1).
6. Patients with a history (or suspected history) of alcohol misuse or any other recreational substance abuse. History of regular alcohol consumption exceeding an average weekly intake of > 21 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 14 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol test at screening.
7. atients who have received treatment with oral, intravenous or intra-articular corticosteroids within 6 weeks of screening or thereafter.
8. Patients with any known hypersensitivity to salbutamol or ipratropium bromide.
9. Patients who have received an investigational drug within 30 days or within five drug half-lives of the investigational drug (whichever is longer).
10. History of elevated blood pressure or blood pressure persistently >140/90 mmHg at screening.
11. Exposure to more than 3 new chemical entities within 12 months prior to the first dosing day. Participation in a trial with a new chemical entity within 4 months before the start of the study.
12. Patients who are pregnant or lactating.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Safety and tolerability of GW856553 in patients with COPD (adverse events, vital signs, clinical laboratory assessments (in particular- liver function test rises), electrocardiographic (ECG) parameters, lung function (FVC, FEV1)
• Withdrawals for adverse events
• Withdrawals for exacerbation of COPD
|
|
| 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 | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
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