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)

NCT02014480 | Completed Phase 3 Results

• 1 other identifier: 116132
• Study Type: interventional
• Target: 207
• Locations: 2 countries
• Sites: 21

Brief Summary

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).

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Long-acting beta-agonist; Chronic Obstructive Pulmonary Disease; Umeclidinium; Long-acting muscarinic antagonist; Vilanterol

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type

  FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM FEV1 was calculated using 0-6 hour post-dose measurements at Day 14 of each TP, which included pre-dose (trough value for Day 14 \[mean of the 23 and 24 hour assessments post Day 13 dosing\]) and post-dose 15 minutes (min), 30 min, and 1, 3, and 6 hours. BL is the mean FEV1 values recorded 30 min and 5 min pre-dose on Day 1 of each TP, mean BL is the mean of the BLs for each participant, and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the Day 14 value minus the BL value for that TP.

  Baseline and Day 14 of each treatment period (up to study day 85)

Secondary Outcomes (3)

• Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP)

  Baseline (BL) and 0-6 hours post-dose (15 minutes, 30 minutes, and 1, 3, and 6 hours post-dose) on Day 1 of each treatment period (up to study day 66)

• Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone

  Baseline and Day 14 of each treatment period (up to study day 85)

• Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period

  Baseline and Day 15 of each treatment period (up to study day 81)

Study Arms (3)

Umeclidinium

EXPERIMENTAL

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.

Device: Umeclidinium 62.5 mcg

Vilanterol

EXPERIMENTAL

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.

Device: Vilanterol 25 mcg

Umeclidinium/Vilanterol

EXPERIMENTAL

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.

Device: Umeclidinium/Vilanterol 62.5/25 mcg

Interventions

Umeclidinium 62.5 mcg DEVICE

Umeclidinium 62.5 mcg once daily in the morning via NDPI.

Umeclidinium

Vilanterol 25 mcg DEVICE

Vilanterol 25 mcg once daily in the morning via NDPI.

Vilanterol

Umeclidinium/Vilanterol 62.5/25 mcg DEVICE

Umeclidinium/Vilanterol 62.5/25 mcg once daily in the morning via NDPI.

Umeclidinium/Vilanterol

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: A current diagnosis of asthma.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (21)

GSK Investigational Site

Humenné, 066 01, Slovakia

Location

GSK Investigational Site

Kráľovský Chlmec, 077 01, Slovakia

Location

GSK Investigational Site

Poprad, 058 01, Slovakia

Location

GSK Investigational Site

Šaľa, 927 01, Slovakia

Location

GSK Investigational Site

Vráble, 952 01, Slovakia

Location

GSK Investigational Site

Donetsk, 83003, Ukraine

Location

GSK Investigational Site

Donetsk, 83099, Ukraine

Location

GSK Investigational Site

Ivano-Frankivsk, 76018, Ukraine

Location

GSK Investigational Site

Kharkiv, 61035, Ukraine

Location

GSK Investigational Site

Kiev, 03680, Ukraine

Location

GSK Investigational Site

Kyiv, 01114, Ukraine

Location

GSK Investigational Site

Kyiv, 02232, Ukraine

Location

GSK Investigational Site

Kyiv, 03038, Ukraine

Location

GSK Investigational Site

Kyiv, 03049, Ukraine

Location

GSK Investigational Site

Kyiv, 03680, Ukraine

Location

GSK Investigational Site

Mykolayiv, 54003, Ukraine

Location

GSK Investigational Site

Poltava, 36024, Ukraine

Location

GSK Investigational Site

Simferopol, 95043, Ukraine

Location

GSK Investigational Site

Sympheropol, 95017, Ukraine

Location

GSK Investigational Site

Vinnytsia, 21018, Ukraine

Location

GSK Investigational Site

Vinnytsia, 21029, Ukraine

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: December 18, 2013
• Study Start: February 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 11, 2013
• Last Updated: February 15, 2018
• Results First Posted: February 11, 2014

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

UA (16); SL (5)