| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10009033 |
| E.1.2 | Term | Chronic obstructive pulmonary disease |
|
| E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy and safety of three doses of
GSK573719 (125, 250, and 500 mcg once daily) compared with placebo in subjects with
COPD in order to inform the selection of an optimal effective and safe dose for future
clinical development programs. |
|
| E.2.2 | Secondary objectives of the trial |
A secondary objective is to evaluate the pharmacokinetic profile of GSK573719 with
repeat dosing in subjects with COPD over 28 days. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Informed Consent: A signed and dated written informed consent prior to study
participation.
2. Gender: Male or female adults.
A female is eligible to enter and participate in this study if she is of non-childbearing
potential (i.e., physiologically incapable of becoming pregnant), including any
female who is post-menopausal. If indicated, menopause can be confirmed by serum
follicle stimulating hormone (FSH) levels >40 mIU/mL and estradiol <40pg/mL
(<140 pmol/L).
3. Age: 40 to 80 years of age, inclusive, at Visit 1
4. Diagnosis: An established clinical history of COPD in accordance with the
definition by the American Thoracic Society/European Respiratory Society
[Celli, 2004] as follows:
Chronic obstructive pulmonary disease is a preventable and treatable disease state
characterized by airflow limitation that is not fully reversible. The airflow limitation
is usually progressive and is associated with an abnormal inflammatory response ofthe lungs to noxious particles or gases, primarily caused by cigarette smoking.
Although COPD affects the lungs, it also produces significant systemic
consequences.
5. Smoking History: Current or previous cigarette smokers with a history of cigarette
smoking of ≥10 pack-years at screening (Visit 1). Previous smokers are defined as
those who have stopped smoking for at least 6 months prior to Visit 1.
Number of pack years = (number of cigarettes per day / 20) x number of years
smoked (e.g., 20 cigarettes per day for 10 years = 10 pack years, or 10 cigarettes per day for 20 years = 10 pack years).
6. Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 and a
post-albuterol/salbutamol FEV1 of ≥35 and ≤70% of predicted normal values at Visit
1 (Screening) calculated using NHANES III reference equations [Hankinson, 1999]. |
|
| E.4 | Principal exclusion criteria |
1. Asthma: A current diagnosis of asthma.
2. Other Respiratory Disorders: Known respiratory disorders other than COPD
including but not limited to α-1 antitrypsin deficiency, active tuberculosis, lung
cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and
interstitial lung disease. Allergic rhinitis is not exclusionary.
3. Lung Resection: Any previous lung resection surgery (e.g., lung volume reduction
surgery or lobectomy)
4. Chest X-Ray: A chest X-ray or computed tomography (CT) scan which reveals
evidence of clinically significant abnormalities not believed to be due to the presence
of COPD. A chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not
available within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray
(or CT scan) is not available in the 6 months prior to Visit 1 the subject will not be
eligible for the study.
5. COPD Medications: Use of oral corticosteroids or antibiotics for an exacerbation of
COPD or a lower respiratory tract infection within 6 weeks prior to Visit 1.
6. Hospitalization: Hospitalization for COPD or pneumonia within 3 months prior to
Visit 1.
7. Other Diseases/Abnormalities: Any significant disease that, in the opinion of the
investigator, would put the safety of the subject at risk through study participation, or which would affect the efficacy analysis if the disease/condition exacerbated during
the study.
8. Morbid Obesity: A body mass index (BMI) value of >35kg/m2.
9. Pacemaker: The presence of a paced rhythm on a 12-lead electrocardiogram (ECG)
which causes the underlying rhythm and ECG to be obscured.
10. 12-Lead ECG: A significantly abnormal 12-lead ECG that results in an active
medical problem. For the purposes of this study, a significantly abnormal ECG that
would preclude a subject from entering the trial is defined as a 12-lead tracing which
is interpreted with, but not limited to, any of the following:
i. Sinus bradycardia <45 beats per minute (bpm) or sinus tachycardia ≥110 bpm
ii. Multifocal atrial tachycardia (wandering atrial pacemaker with rate >100 bpm)
iii. PR interval >240msec
iv. Evidence of Mobitz II second degree or third degree atrioventricular (AV) block
v. Pathological Q waves (defined as wide [>0.04 seconds] and deep [>0.4 mV
(4mm with 10 mm/mV setting)] or >25% of the height of the corresponding R
wave, providing the R wave was >0.5 mV [5 mm with 10 mm/mV setting],
appearing in at least two contiguous leads.
Note: prior evidence (i.e., ECG obtained at least 12 months prior) of
pathological QT waves that are unchanged are not exclusionary.
vi. Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal
premature ventricular complexes.
vii. QTc(F) ≥450 msec or uncorrected QT > 600 msec or an ECG that is unsuitable
for QT measurements (e.g., poor defined termination of the T wave)
Note: QTc(F) ≥450 msec or uncorrected QT >600 msec should be confirmed by
three readings at least 5 minutes apart.
viii. ST-T wave abnormalities (excluding non-specific ST-T wave abnormalities)
ix. Right or left complete bundle branch block
x. Clinically significant conduction abnormalities (e.g., left bundle branch block,
Wolff-Parkinson-White syndrome)
xi. Clinically significant arrhythmias (e.g., atrial fibrillation with rapid ventricular
response, ventricular tachycardia)
Investigators will be provided with ECG reviews conducted by an independent
cardiologist to assist in evaluation of subject eligibility.
Please refer to protocol for remaining criteria
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is change from baseline in trough FEV1 at Day 29. Baseline is
defined as the mean of the two pre-dose values obtained 30 minutes pre-dose and
immediately pre-dose [time 0] on Day 1. Trough is defined as the mean of the FEV1
values obtained 23 and 24 hours after the dose administered on Day 28. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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