| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Chronic Obstructive Pulmonary Disease (COPD) | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10010952 | | E.1.2 | Term | COPD | | E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders | |
| 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 | | The primary objective is to compare the efficacy of two doses of GSK573719/GW642444 Inhalation Powder (125mcg/25mcg and 62.5/25mcg once-daily) with GSK573719 (125mcg once daily) and with tiotropium (18mcg once-daily) over 24 weeks for the treatment of subjects with COPD. | |
| E.2.2 | Secondary objectives of the trial | | Secondary objectives are to compare effects of two doses of GSK573719/GW642444 Inhalation Powder (125mcg/25mcg and 62.5/25mcg once-daily) with GSK573719 (125mcg once daily) and with tiotropium (18mcg once-daily) on safety and quality of life assessments over 24 weeks in subjects with COPD. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Type of subject: Outpatient.
2. Informed Consent: A signed and dated written informed consent prior to study
participation.
3. Age: Subjects 40 years of age or older at Visit 1.
4. Gender: Male or female subjects.
A female is eligible to enter and participate in the study if she is of:
Non-child bearing potential (i.e. physiologically incapable of becoming pregnant,
including any female who is post-menopausal or surgically sterile). Surgically sterile
females are defined as those with a documented hysterectomy and/or bilateral
oophorectomy or tubal ligation. Post-menopausal females are defined as being
amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age
appropriate, > 45 years, in the absence of hormone replacement therapy. However in questionable cases, post-menopause status may be confirmed by analysis of a blood sample with FSH > 40MIU/ml and estradiol <40pg/ml (<140 pmol/L) as
confirmatory.
OR
Child bearing potential, has a negative pregnancy test at screening, and agrees to
one of the following acceptable contraceptive methods used consistently and
correctly (i.e. in accordance with the approved product label and the instructions of
the physician for the duration of the study – screening to follow-up contact):
• Abstinence
• Oral Contraceptive, either combined or progestogen alone
• Injectable progestogen
• Implants of levonorgestrel
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP
effectiveness criteria as stated in the product label
• Male partner sterilization (vasectomy with documentation of azoospermia) prior
to the female subject's entry into the study, and this male is the sole partner for
that subject. For this definition, “documented” refers to the outcome of the
investigator's/designee’s medical examination of the subject or review of the
subject's medical history for study eligibility, as obtained via a verbal interview
with the subject or from the subject’s medical records.
• Double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent
(foam/gel/film/cream/suppository)
5. 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 of
the lungs to noxious particles or gases, primarily caused by cigarette smoking.
Although COPD affects the lungs, it also produces significant systemic
consequences.
6. Smoking History: Current or former cigarette smokers with a history of cigarette
smoking of ≥10 pack-years [number of pack years = (number of cigarettes per day /
20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10
cigarettes per day for 20 years)]. Previous smokers are defined as those who have
stopped smoking for at least 6 months prior to Visit 1.
7. Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a
post-albuterol/salbutamol FEV1 of ≤70% of predicted normal values calculated using
NHANES III reference equations at Visit 1 [Hankinson, 1999; Hankinson, 2010]
8. Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnea Scale(mMRC) at Visit 1 | |
| E.4 | Principal exclusion criteria | Deviations from exclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Pregnancy: Women who are pregnant or lactating or are planning on becoming
pregnant during the study
2. Asthma: A current diagnosis of asthma
3. Other Respiratory Disorders: Known respiratory disorders other than COPD
including but not limited to α-1 antitrypsin deficiency, active tuberculosis,
bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial
lung disease. Allergic rhinitis is not exclusionary.
4. Other Diseases/Abnormalities: Subjects with historical or current evidence of
clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
immunological, endocrine (including uncontrolled diabetes or thyroid disease) or
hematological abnormalities that are uncontrolled and/or a previous history of cancer
in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has
been resected for cure is not exclusionary). Significant is defined as any disease that,
in the opinion of the investigator, would put the safety of the subject at risk through
participation, or which would affect the efficacy or safety analysis if the
disease/condition exacerbated during the study.
5. Chest X-Ray: A chest X-ray or computed tomography (CT) scan that 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.
6. Contraindications: A history of allergy or hypersensitivity to any
anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or
magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic
hypertrophy or bladder neck obstruction that, in the opinion of the study physician
contraindicates study participation or use of an inhaled anticholinergic.
7. Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to
Visit 1
8. Lung Resection: Subjects with lung volume reduction surgery within the 12 months
prior to Screening (Visit 1)
9. 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG
conducted at Visit 1, including the presence of a paced rhythm on a 12-lead
electrocardiogram (ECG) which causes the underlying rhythm and ECG to be
obscured. Investigators will be provided with ECG reviews conducted by a
centralized independent cardiologist to assist in evaluation of subject eligibility.
Specific ECG findings that preclude subject eligibility are listed in Appendix 5. The
study investigator will determine the medical significance of any ECG abnormalities
not listed in Appendix 5 of protocol.
10. Screening Labs: Significantly abnormal finding from clinical chemistry or
hematology tests at Visit 1
11. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4
hour period required prior to spirometry testing at each study visit
12. Medications prior to Screening: Use of the following medications according to the
following defined time intervals prior to Visit 1: Please see table page 24 of protocol.
13. Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy
prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., ≤12 hours per day) is not exclusionary.
14. Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed
use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized
therapy.
15. Pulmonary Rehabilitation Program: Participation in the acute phase of a
pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are
in the maintenance phase of a pulmonary rehabilitation program are not excluded.
16. Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse
within 2 years prior to Visit 1.
17. Affiliation with Investigator Site: Is an investigator, sub-investigator, study
coordinator, employee of a participating investigator or study site, or immediate
family member of the aforementioned that is involved in this study.
18. Previous use of study drug: Previous exposure to GSK573719,
GSK573719/GW642444 combination, GW642444 (vilanterol) and fluticasone
furoate/GW642444 combination.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | The primary endpoint is the clinic visit pre-dose trough FEV1 on Treatment Day 169.
Trough FEV1 on Treatment Day 169 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 168 (i.e. at Week 24).
| |
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description | |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | |
| 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 | 17 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
