Study To compare Umeclidinium/Vilanterol combination with Tiotropium in Chronic Obstructive Pulmonary Disease (COPD) Patients Who Continue To have Symptoms on Tiotropium.

• Conditions: Chronic Obstructive Pulmonary Disease (COPD) which may also be called emphysema or chronic bronchitis; MedDRA version: 16.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2012-005007-41-ES
• Lead Sponsor: GlaxoSmithKline, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-24
• Last Update Posted: 12 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 666

Inclusion Criteria

Subjects eligible for enrolment in the run-in phase must be able to read and understand the study documentation relating to informed consent and patient questionnaires and meet all the following criteria:
1. 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.
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. Bronchodilator Treatment: Subjects must have been on tiotropium either via the HandiHaler device or Respimat for at least 3 months prior to screening.
6. COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004].
7. 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.
Note: Pipe and/or cigar use cannot be used to calculate pack-year history
8. Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a pre and post-albuterol/salbutamol FEV1 of <=70% and >=50% predicted normal values calculated using NHANES III reference equations at Visit 1 [Hankinson, 1999; Hankinson, 2010].
9. Dyspnoea: A score of >=2 on the Modified Medical Research Council Dyspnoea Scale (mMRC) at Visit 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F

Exclusion Criteria

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 ?-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
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. Exacerbations: Has had more than 1 COPD exacerbation in the past 12 months. Subjects with an exacerbation within 6 weeks prior to Visit 1 are excluded from study.
COPD exacerbation is defined as worsening symptoms of COPD requiring the use of any additional treatment -other than the prescribed bronchodilator- such as the use of antibiotics, systemic corticosteroids, and/or emergency treatment or hospitalisation.
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. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
8. 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 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 3.
The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 3.
9. Inhaled Steroids: Currently taking an inhaled corticosteroid as part of their maintenance treatment for COPD. (Maintenance is defined as daily use for ?1month)
10. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
11. Medications Prior to Screening: Use of the following medications (see Protocol, Section 4.3) according to the following defined time intervals prior to Visit 1.
12. Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified