A 14 week study where each subject takes 3 medicines (each for 2 weeks) being developed to treat COPD

• Register: EUCTR
• Last refreshed on: 18 April 2016
• Main ID: EUCTR2011-005913-35-SK
• Date of registration: 09/03/2016
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A 14 week study where each subject takes 3 medicines (each for 2 weeks) being developed to treat COPD
• Scientific title: A Randomized, Double-Blind, 3-Way, Cross-Over Study to Evaluate Lung Function Response after Treatment with Umeclidinium 62.5mcg, Vilanterol 25mcg, and Umeclidinium/Vilanterol 62.5/25mcg Once-Daily in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
• Date of first enrolment: 27/06/2012
• Target sample size: 172
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005913-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Slovakia, Ukraine

Contacts

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Limited

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Type of Patient: 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 Follicle-stimulating Hormone (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 (ATS/ERS) [Celli , 2004].
6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of >= 10 pack-years at 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, or 10 cigarettes per day for 20 years]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
7. Severity of Disease: A pre- and post-salbutamol FEV1/FVC ratio of <0.70 and a pre- and post-salbutamol FEV1 of <=70% of predicted normal values at Visit 1 calculated using Nutrition Health and Examination Survey (NHANES) III reference equations [Hankinson, 2010].

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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 alpha-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 condition in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or 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 safety analysis if the disease/condition exacerbated during the study.
5. 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 of 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.
6. Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
7. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
8. 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1, 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 2. The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 2.
9. Screening Labs: Significantly abnormal finding from clinical chemistry or hematology tests at Visit 1 as determined by the study investigator.
10. Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit and at each spirometry test performed at home.
11. Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1 (see table in Section 4.3 of Protocol)
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 (i.e., ?12 hours per day) is not exclusionary.
13. Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol, ipratropium bromide) via nebulized therapy
14. Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 w

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 18.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Umeclidinium/Vilanterol
Product Code: GSK573719/GW642444
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Umeclidinium/Vilanterol
Current Sponsor code: GSK573719/GW642444
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 62.5/25-

Product Name: Umeclidinium
Product Code: GSK573719
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Umeclidinium
Current Sponsor code: GSK573719
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 62.5-

Product Name: Vilanterol
Product Code: GW642444
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Umeclidinium/Vilanterol
Current Sponsor code: GSK573719/GW642444
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 125/25-
INN or Proposed INN: Vilanterol
Current Sponsor code: GW642444
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the lung function response following treatment with UMEC 62.5mcg, VI 25mcg, and UMEC/VI 62.5/25mcg administered once-daily via the Novel Dry Powder Inhaler (NDPI) in subjects with COPD.

Primary end point(s): The primary efficacy endpoint is the weighted mean FEV1 over 0-6 hours post-dose on Day 14 of each treatment period.

Secondary Objective: NOT

Timepoint(s) of evaluation of this end point: 0-6 hours post-dose on Day 14 of each treatment period

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 0-6 hours post dose n Day 14 for Proportion of Subjects endpoints.
Day 15 for Trough FEV1

Secondary end point(s): • Proportion of subjects who were responsive to UMEC/VI, UMEC or VI according to FEV1 at Day 1 (responsive defined as an increase from baseline of at least 12% and 200mL at any time over 0-6 h post-dose)
• Proportion of subjects who had a larger change from baseline in 0-6 h WM FEV1 on Day 14 with UMEC/VI compared with UMEC and VI alone
• Trough FEV1 on Day 15

Secondary ID(s)

DB2116132

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited