COPD patients (moderate)
Conditions
Interventions
Product Name: GW642444M
Product Code: GW642444M
Pharmaceutical Form: Inhalation powder, pre-dispensed
Current Sponsor code: GW642444M
Concentration unit: µg microgram(s)
Concentration type: equal
Conc
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Male subjects or female subjects of non child bearing potential (i.e. post-menopausal or surgically sterile) between 40 and 75 years of age at screening Post-menopausal females are defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to laboratory ranges) at screening. Surgically sterile females are defined as those with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy or tubal ligation. 2. Subjects with a 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. 3. Body weight equal or greater than 50 kg and BMI within the range 18 - 32 kg/m2. 4. Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent). A former smoker is defined as a subject who has not smoked for equal or greater than 12 months at screening. 5. Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects who have a past or present disease, which may affect the outcome of this study. 2. Women who are pregnant or lactating or of child bearing potential. 3. Subjects with a primary diagnosis of asthma. (Subjects with a prior history of asthma are eligible if COPD is currently their primary diagnosis). 4. Subjects with alpha-1 antitrypsin deficiency as the underlying cause of COPD. 5. Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease or other active pulmonary disease. 6. Subjects with lung volume reduction surgery within the 12 months prior to screening. 7. Subject has had an upper respiratory tract infection in the 4 weeks prior to the screening visit and throughout the duration of the study. 8. Subjects with hypoxaemia, or subjects receiving treatment with long-term oxygen therapy (LTOT). All subjects must have an Oxygen (O2) saturation of greater or equal than 88% on room air. 9. Subjects with a positive Hepatitis B surface antigen or positive hepatitis C antibody pre-study or at screening. 10. Subjects with poorly controlled COPD: • acute worsening of COPD that is managed by subject at home with oral corticosteroids or antibiotics in the 6 weeks prior to screening, or • more than two exacerbations in the previous 12 months prior to screening that required a course of oral corticosteroids or antibiotics, or, for which the subject was hospitalised. 11. Subjects with a blood potassium level <3.5 mmol/L at screening. 12. Subjects with clinically important cardiovascular, neurological, psychiatric, renal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled. 13. Uncontrolled hypertension defined as a mean supine blood pressure equal to or higher than 160/90 mmHg at screening in subjects not receiving medication for hypertension. Or Uncontrolled hypertension defined as a mean supine blood pressure equal to or higher than 150/90 mmHg at screening in subjects receiving medication for hypertension (please refer to exclusion criteria for prohibited medications). 14. A mean heart rate outside the range 50 – 90 beats per minute (bpm) at screening. 15. Subjects with carcinoma that has not been in complete remission for at least 5 years. 16. Subjects with a history of hypersensitivity to any beta-agonist or to ipratropium bromide. In addition patients with a history of milk protein allergy will also be excluded. 17. Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years. Abuse of alcohol is defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females).. 18. Subjects who are predicted to be medically unable to withhold their rescue medication for the 6 hour period required prior to spirometry testing at each study visit would be ineligible for the study. 19. The subjects must not have used the medications listed in Section 9.2 prior to screening for the required interval. 20. Subjects receiving treatment with tricyclic antidepressants, Monoamine Oxidase Inhibitors (MAOI), or beta-adrenergic antagonist would be ineligible for the study. 21. Subjects receiving treatment with long term or short-term oxygen therapy or who require nocturnal positive pressure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of single doses of GW642444M with magnesium stearate (25, 50 and 100 mcg) in COPD patients;Secondary Objective: To evaluate the pulmonary and extra-pulmonary pharmacodynamic effects of single doses of GW642444M (25, 50 and 100 mcg) in COPD patients To evaluate the systemic pharmacokinetics of GW642444, GI179710 (triphenylacetate counterion) and the metabolites, GW630200 and GSK 932009 following single doses of GW642444M (25, 50 and 100 mcg) in COPD patients To assess the safety and tolerability, PK and PD parameters of a single inhaled dose of GW642444H (100 mcg) and obtain an estimate of the difference between inhaled dose of GW642444H (100 mcg) and a single inhaled dose GW642444M (100 mcg) in COPD patients To characterise lung dose-response and systemic exposure-response relationships ;Primary end point(s): General safety and tolerability, including adverse events, laboratory safety tests (haematology, clinical chemistry and urinalysis), vital signs, 12-lead ECG and, Holter monitoring. | — |
Countries
Germany
Outcome results
None listed