| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Persistent asthmatic subjects |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| 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 determine the trough (mean of 23 and 24 hour) FEV1 after 14 day repeat doses of
inhaled GSK159797 (10, 15, and 20μg) administered once daily in persistent
asthmatic subjects. |
|
| E.2.2 | Secondary objectives of the trial |
• To determine the trough (mean of 11 and 12 hour) FEV1 after 14 day repeat doses of inhaled Salmeterol (50μg) administered twice daily in persistent asthmatic subjects.
• To determine the rate of onset of bronchodilation of single and repeat dose inhaled
GSK159797 (10, 15 and 20μg once daily) and Salmeterol (50μg twice daily) in
persistent asthmatic subjects.
• To assess the safety and tolerability of a single and repeated inhaled doses of
GSK159797 (10, 15 and 20μg once daily) and Salmeterol (50μg twice daily) in
persistent asthmatic subjects.
• To assess the systemic pharmacodynamics of GSK159797 following single and
repeat inhaled doses (10, 15 and 20μg once daily) and Salmeterol (50μg twice daily)
in persistent asthmatic subjects.
• To assess the pharmacokinetics of GSK159797 and Salmeterol following single and
repeat doses of inhaled GSK159797 (10, 15, and 20μg once daily) or Salmeterol
(50μg twice daily) in persistent asthmatic subjects. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Subjects with a documented history of persistent asthma, with the exclusion of other significant pulmonary diseases (e.g. chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis or bronchopulmonary dysplasia).
2.Female subjects aged between 18 to 70 years.
Females are eligible to participate only if they are currently non-pregnant and non-lactating. Females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:
•Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject
•Implants of levonorgestrel
•Injectable progestogen
•Oral contraceptive (either combined estrogen/progestin or progestin only)
•Any intrauterine device (IUD) with a documented failure rate of less than 1% per year, or
•Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days).
•The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds/90 kilos)
•Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all females. This test will be performed at Screening and Day 1 and Day 7 of each treatment period, and follow up.
3.Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of less than or equal to 10 pack years.
Pack years = Number of cigarettes per day/20 x Number of years smoked
4.Subjects with clinically stable persistent asthma within the 4 weeks preceding the screening visit and with a screening pre-bronchodilator FEV1 between 60 and 90% predicted (having abstained from bronchodilators for the required period). Predicted values are based on the ECCS 1993 normal ranges.
5.During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of greater than or equal to 12.0% over baseline and an absolute change of greater than or equal to 300mL within 30 minutes following a single 400mcg salbutamol dose.
6.Subjects who are able and willing to give written informed consent to take part in the study.
7.Subjects who are currently taking ICS at a total daily dose of 200 to 500mcg of FP or equivalent ICS.
|
|
| E.4 | Principal exclusion criteria |
1.Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the safety of the subject or outcome of this study. The list of additional excluded conditions/diseases includes, but is not limited to the following:
Congestive heart failure, Immunologic compromise, Known aortic aneurysm, Current malignancy [history of malignancy is acceptable only if subject has been in remission for one year prior to Visit 1 (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months prior to Visit 1)], Clinically significant coronary heart disease, Tuberculosis (current or quiescent), Clinically significant cardiac arrhythmia, Cushing’s disease, Stroke within 3 months of Visit 1, Addison’s disease, Uncontrolled hypertension (a systolic blood pressure >170, or diastolic blood pressure >100), Uncontrolled diabetes mellitus, Poorly controlled peptic ulcer, Recent history of drug or alcohol abuse, Hematologic, hepatic, or renal disease
2.A screening Holter ECG tracing that reveals clinically concerning arrhythmias (including, but not limited to, ventricular ectopic runs of greater than or equal to 4 beats, R on T phenomena, bigeminy, trigeminy).
3.A mean QTc(B) value at screening >450 msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
4.Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit
5.Subjects with a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with either respiratory arrest or hypoxic seizures.
6.Asthma exacerbations requiring treatment with oral corticosteroids: any exacerbations within 3 months of the screening visit or two or more exacerbations within 6 months of the screening visit or admittance to hospital for an asthma exacerbation within 1 year of the screening visit.
7.Subjects who have taken high doses of inhaled (>500mcg FP/day or equivalent) or oral steroids within 8 weeks of the screening visit or oral corticosteroids within 12 weeks of the screening visit.
8.Subjects who have changed their inhaled corticosteroid treatment within the last 6 weeks before screening or can be expected to do so during the study.
9.Subjects who have received a new chemical entity drug, or have received a marketed compound in a clinical study, within 3 months of the screening visit.
10.Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of GSK159797 inhalation powder (i.e., lactose or COA).
11.Subjects with a positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody or HIV (if tested according to site SOPs) result within 3 months of the start of the study.
12.Neurological or psychiatric disease or history of drug or alcohol abuse which would interfere with the subject’s proper completion of the protocol requirements, including compliance. Abuse of alcohol is defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units.
13.Subjects who have a screening haemoglobin value <110mg/L.
14.Subjects with known hypersensitivity to salbutamol or salmeterol or any ingredients in their preparations
15.History of severe milk protein allergy.
16.Subjects weighing <50kg.
17.Subjects who have participated in any GSK study involving administration of COA.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
To determine the trough (mean of 23 and 24 hour) FEV1 after 14 day repeat doses of
inhaled GSK159797 (10, 15, and 20μg) administered once daily in persistent
asthmatic subjects. |
|
| 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 | 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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