A randomised, double-blind, placebo-controlled, dose ascending, 2-cohort, parallel group study to examine the safety, tolerability and pharmacokinetics of once-daily inhaled doses of GSK573719 formulated with the excipient Magnesium Stearatein COPD subjects for 7 days.
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)
- Registration Number
- EUCTR2008-001095-77-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of repeat inhaled doses of GSK573719 MgSt<br>(inhaled once daily for 7 days) in COPD subjects.;Secondary Objective: To assess the pharmacokinetics of GSK573719 MgSt following repeat inhaled doses<br>(inhaled once daily for 7 days) in COPD subjects.;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.<br><br>The following endpoints will be derived for the Vital Signs (heart rate) on Days 1 & 7:<br>• Maximum value (0-4 hour)<br>• Weighted Mean (0-4 hour)<br><br>The following endpoints will be derived for the 24h Holter monitoring (heart rate) on<br>Screening and Day 7:<br>• Maximum value (0-24 hours)<br>• Mean (0-24 hours)
- Secondary Outcome Measures
Name Time Method