A Cross-Over Study to Evaluate Lung Function Response After Treatment With Umeclidinium (UMEC) 62.5 Micrograms (mcg), Vilanterol (VI) 25 mcg, and Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 mcg Once-Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Device: Vilanterol 25 mcg; Device: Umeclidinium/Vilanterol 62.5/25 mcg; Device: Umeclidinium 62.5 mcg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02014480

116132

Details and patient eligibility

About

This is a multicenter, randomized, double-blind, 3-way crossover study to evaluate the lung function response to UMEC 62.5 mcg, VI 25 mcg, and UMEC/VI 62.525 mcg, administered once-daily via a novel dry powder inhaler (NDPI) over 14 days in subjects with COPD.

The study consisted of Run in Phase (5 to 7 days), Treatment Phase (made up of 3 treatment periods of 14 days each separated by 10 to 14 days Washout Period) and Follow-up Phase (7 to 9 days after completion of final visit or premature discontinuation). Eligible subjects will be randomized to a sequence of UMEC 62.5 mcg, VI 25 mcg, and UMEC/VI 62.5/25 mcg such that all subjects will receive each treatment.

Serial spirometry assessments will be conducted on Day 1 and Day 14 and trough spirometry will be conducted on Day 2 and Day 15 of each treatment period. On Day 1 and 14 of each treatment period vital signs will be assessed and adverse event (AE)s will be recorded throughout the total duration of the study (approximately 12 weeks).

Enrollment: 207 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type of Patient: Outpatient.
• Informed Consent: A signed and dated written informed consent prior to study participation.
• Age: Subjects 40 years of age or older at Visit 1.
• Gender: Male or female subjects.
• A female is eligible to enter and participate in the study if she is of: Non-child bearing potential. 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 acceptable contraceptive methods used consistently and correctly.
• Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
• Smoking History: Current or former cigarette smokers with a history of cigarette smoking of >= 10 pack-years at Visit 1.
• Severity of Disease: A pre- and post-salbutamol FEV1/forced vital capacity (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.

Exclusion criteria

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: A current diagnosis of asthma.
• 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. 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).
• 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.
• Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
• Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
• 12-Lead ECG: An abnormal and significant electrocardiogram (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. The study investigator will determine the medical significance of any ECG abnormalities.
• 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.
• Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: Depot corticosteroids (12 weeks), oral or parenteral corticosteroids (6 weeks), antibiotics (for lower respiratory tract infection) (6 weeks), cytochrome P450 3A4 strong inhibitors2 (6 weeks), long-acting beta agonist (LABA)/ inhaled corticosteroid (ICS) combination products if LABA/ICS therapy is discontinued completely (30 days), use of ICS at a dose >1000 mcg/day of fluticasone propionate or equivalent (30 days), initiation or discontinuation of ICS use (30 days), tiotropium (7 days), roflumilast (14 days), theophyllines (48 hours), oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours), oral beta-agonists long-acting (48 hours), short-acting (12 hours), inhaled long acting beta2-agonists (LABA, e.g., salmeterol, formoterol, indacaterol) (48 hours), LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy (48 hours for the LABA component), inhaled sodium cromoglycate or nedocromil sodium (24 hours), inhaled short acting beta2-agonists (4 hours), inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (4 hours) and any other investigational medication 30 days or within 5 drug half-lives (whichever is longer).
• 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.
• 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.
• 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.
• Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
• 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.
• Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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207 participants in 3 patient groups

Umeclidinium

Experimental group

Description:

All subjects will receive UMEC in the dose of 62.5 mcg as inhalation powder in the NDPI once daily in the morning over 14 days in a cross over design.

Treatment:

Device: Umeclidinium 62.5 mcg

Vilanterol

Experimental group

Description:

All subjects will receive VI in the dose of 25 mcg as inhalation powder in the NDPI once daily in the morning over 14 days in a cross over design.

Treatment:

Device: Vilanterol 25 mcg

Umeclidinium/Vilanterol

Experimental group

Description:

All subjects will receive UMEC/VI in the dose of 62.5/25 mcg as inhalation powder in the NDPI once daily in the morning over 14 days in a cross over design.

Treatment:

Device: Umeclidinium/Vilanterol 62.5/25 mcg