| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease (COPD) |
|
| 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 repeat inhaled doses of GSK573719 MgSt
(inhaled once daily for 7 days) in COPD subjects. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics of GSK573719 MgSt following repeat inhaled doses
(inhaled once daily for 7 days) in COPD subjects. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female between 40 and 75 years of age.
2. A female subject is eligible to participate if she is of:
Non childbearing potential including pre-menopausal females with documented
(medical report verification) hysterectomy, bilateral salpingectomy or bilateral
oophrectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and
estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy
with or without hysterectomy.
3. Male subjects must agree to use one of the contraception methods listed in
Section 8.1. This criterion must be followed from the time of the first dose of study
medication until 90 days post-last dose.
4. Subject diagnosed with COPD, as defined by the GOLD guidelines.
5. BMI within the range 18 – 34 kg/m2 (inclusive).
6. Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (Pack years = (cigarettes per day smoked/20) x number of years smoked)).
7. Average QTcB or QTcF ≤ 450 msec taken from triplicate assessments at screening;
or QTc ≤ 480 msec in subjects with Bundle Branch Block.
8. Subject has a post-bronchodilator (400 μg salbutamol) FEV1 of ≥ 35% to ≤ 80% of predicted normal.
9. Subject has FEV1/FVC < 0.7 post-bronchodilator (400 μg salbutamol).
10. Subjects have a 24hour holter recording that is within normal limits for the
individual and does not demonstrate any clinically important abnormality that, in the
opinion of the investigator, would make the subject unsuitable for participation in the
study.
11. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
12. Subject is available to complete all study measurements and procedures. |
|
| E.4 | Principal exclusion criteria |
1. Subjects who have a past or present disease, which as judged by the Investigator, may affect subject safety or influence the outcome of the study.
3. The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs
that will be screened for include amphetamines, barbiturates, cocaine and opiates.
The detection of drugs taken for a legitimate medical purpose would not necessarily
be an exclusion to study participation. The detection of alcohol would not be an
exclusion at screening but would need to be negative pre-dose and during the study.
4. Female subject has a positive pregnancy test.
5. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
6. A positive test for HIV antibody (if tested, according to local SOP's).
7. History of high alcohol consumption within 1 month of the study 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). One
unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits
or 1 glass (125ml) of wine.
8. The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).
9. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
10. History of sensitivity to any of the study medications, or components thereof
(including allergy to milk protein/lactose) or a history of drug or other allergy that, in
the opinion of the Investigator or GSK Medical Monitor, contraindicates their
participation.
11. Subject has donated a unit (400 mL) of blood within 60 days of screening or, intends to donate during the study.
12. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
13. Unwillingness or inability to follow the procedures outlined in the protocol.
14. The subject is unable to use the novel dry powder inhaler correctly.
15. The subject requires treatment for prostate hypertrophy.
16. The subject has a history of narrow angle glaucoma. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
General safety and tolerability endpoints: adverse events, blood pressure, heart rate, 12-lead ECG, 24h Holter monitoring, lung function (FEV1), rescue medication usage (total number of salbutamol doses taken over the 7-day study period) and clinical laboratory safety tests.
The following endpoints will be derived for the Vital Signs (heart rate) on Days 1 & 7:
• Maximum value (0-4 hour)
• Weighted Mean (0-4 hour)
The following endpoints will be derived for the 24h Holter monitoring (heart rate) on
Screening and Day 7:
• Maximum value (0-24 hours)
• Mean (0-24 hours) |
|
| 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 | No |
| E.6.6 | Pharmacokinetic | Yes |
| 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| 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 | 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 |
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