A 24 Week Efficacy Study of Inhaled Umeclidinium (UMEC) in Patients of Chronic Obstructive Pulmonary Disease (COPD) Using a Novel Dry Powder Inhaler (NDPI)

NCT02184611 | Completed Phase 3 Results

• 1 other identifier: 117410
• Study Type: interventional
• Target: 308
• Locations: 2 countries
• Sites: 26

Brief Summary

Studies to date provides substantial evidence for the effectiveness for UMEC 62.5 microgram (mcg) as a long term maintenance therapy for the treatment of COPD; this study further evaluates the efficacy and safety of UMEC 62.5 mcg administered once-daily (OD) for 24 weeks via a NDPI compared with placebo in Asian subjects with COPD. Over approximate 27 weeks of entire study duration, 10 study clinic visits will be conducted on an outpatient basis. Pre-screening visit will be conducted for the informed consent form, review demography, COPD history and COPD concomitant medications. Subjects meeting the eligibility criteria at screening will complete a 7 to 14 day Run-in period and will be provided with albuterol/salbutamol as rescue medication on an "as-needed" basis. Further, subjects will be randomized to the UMEC 62.5 mcg or matching placebo in a 1:2 ratio for 24 week treatment period. A follow up for adverse event assessment will be scheduled approximately 7 days after the treatment period or the Early Withdrawal Visit.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

lung function; Umeclidinium; GSK573719; anticholinergic; novel dry powder inhaler; long-acting muscarinic receptor antagonist; Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough (Pre-bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) on Treatment Day 169

  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 169 was defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Treatment Day 168 (i.e. at Week 24). Baseline FEV1 is defined as the mean of the two assessments made pre-dose at Visit 2 (Day 1). Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value. Modified intent-to-treat (mITT) Population comprised of all participants randomized to treatment who received at least one dose of the study medication in the treatment period.

  Baseline (Day 1) and Day 169

Secondary Outcomes (14)

• Transition Dyspnea Index (TDI) Focal Score at Week 24 (Day 168)

  Week 24 (Day 168)

• Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose on Day 1

  Baseline (pre-dose on Day 1) and Day 1 (0 to 6 hours)

• Number of Participants With Adverse Events (AE) and Serious AE (SAE)

  Up to Day 178

• Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Day 1) to Day 169 (Visit 9)

• Change From Baseline in Vital Sign Parameter: Pulse Rate

  Baseline (Day 1) to Day 169 (Visit 9)

Study Arms (2)

Umeclidinium bromide

EXPERIMENTAL

Subjects meeting the eligibility criteria will complete a 7 to 14 day run-in period and will be randomized to receive UMEC Inhalation Powder 62.5 mcg OD over a period of 24 weeks

Drug: Umeclidinium bromide

Placebo

PLACEBO COMPARATOR

Subjects meeting the eligibility criteria will complete a 7 to 14 day run-in period and will be randomized to receive matching placebo of UMEC Inhalation Powder OD over a period of 24 weeks

Drug: Placebo

Interventions

Umeclidinium bromide DRUG

Blended with lactose and magnesium stearate dry white powder of umeclidinium 62.5 mcg to be inhaled via a NDPI

Umeclidinium bromide

Placebo DRUG

Blended with lactose and magnesium stearate dry white powder to be inhaled via a NDPI

Placebo

Eligibility Criteria

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

You may qualify if:

• Type of subject: outpatient, Asian ancestry.
• Informed Consent: A signed and dated written informed consent prior to study participation.
• Age: 40 years of age or older at Screening (Visit 1).
• Gender: Male or female subjects are eligible to participate in the study. 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) \>40 million international units per milliliter (MIU/ml) and estradiol \<40 picogram (pg) /ml (\<140 picomole per liter (pmol/L) as confirmatory. OR Child bearing potential, provided the subject 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)\\ 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\\ Double barrier method condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).
• COPD History: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society as follows: COPD 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.
• Tobacco Use and Smoking History: Current or former cigarette smokers with a history of cigarette smoking of \>= 10 pack-years \[Number of pack years = (number of cigarettes per day /20) x number of years smoked (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack years)\]. Former 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. COPD patients who only use a pipe and/or cigar are not eligible.
• Severity of Disease: A pre and post-salbutamol/albuterol FEV1/FVC ratio of \<0.70 and a pre and post-salbutamol/albuterol FEV1 of \<=70% of predicted normal values calculated using National Health and Nutrition Examination Survey III reference equations at Visit 1.
• Dyspnea: A score of \>=2 on the Modified Medical Research Council Dyspnoea Scale (mMRC) at Screening (Visit 1)

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.
• 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.
• 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 Screening (Visit 1).
• Screening Labs: Significantly abnormal findings from clinical chemistry and haematology tests at Visit 1.
• Medications Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
• Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1 is presented as Medication with Time Interval Prior to Visit 1: Depot corticosteroids (12 weeks); Systemic, oral, parenteral (intra-articular) corticosteroids (4 weeks); Antibiotics (for lower respiratory tract infection) (4 weeks); inhaled corticosteroid/ long-acting beta agonist (ICS/LABA) combination products if ICS/LABA therapy is discontinued completely (30 days); Use of ICS at a dose \>1000mcg/day of fluticasone propionate or equivalent (30 days); Initiation or discontinuation of ICS use (30 days); Phosphodiesterase 4 (PDE4) inhibitors (roflumilast) (14 days); Long-acting anticholinergics (e.g.,tiotropium and aclidinium, glycopyronium) (7 days); Theophyllines (12 hours stable dose of theophylline alone is allowed during the study but must be withheld 12 hours prior to each study visit); Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours); Oral beta2-agonists (Long- acting 48 hours, Short -acting 12 hours); Olodaterol and Indacaterol (inhaled long-acting beta2-agonist) (14 days); Salmeterol, formoterol, (inhaled long-acting beta2-agonist) (48 hours); LABA/ ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy (48 hours for LABA component); Inhaled sodium cromoglycate or nedocromil sodium (24 hours); Inhaled short acting beta2-agonists (4 hours); Inhaled short-acting anticholinergics (e.g. ipratropium bromide) (4 hours, stable dose of ipratropium alone is allowed during the study, provided that the subject is on a stable dose regimen from Screening \[Visit 1 and remains so throughout the study\] but must be withheld 4 hours prior to each study visit); Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (4 hours); Any other investigational drug (30 days or 5 half lives, whichever is longer). Note: Further details related to allowable dosage of above listed medications will be explained by the Investigator)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (26)

GSK Investigational Site

Guangzhou, Guangdong, 510630, China

Location

GSK Investigational Site

Zhanjiang, Guangdong, 524001, China

Location

GSK Investigational Site

Haikou, Hainan, 570311, China

Location

GSK Investigational Site

Hohhot, Inner Mongolia, 010017, China

Location

GSK Investigational Site

Wuxi, Jiangsu, 214023, China

Location

GSK Investigational Site

Nanchang, Jiangxi, 330006, China

Location

GSK Investigational Site

Changchun, Jilin, 130041, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110004, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110015, China

Location

GSK Investigational Site

Yinchuan, Ningxia, 750004, China

Location

GSK Investigational Site

Jinan, Shandong, 250013, China

Location

GSK Investigational Site

Qingdao, Shandong, 266071, China

Location

GSK Investigational Site

Taiyuan, Shanxi, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, China

Location

GSK Investigational Site

Beijing, 100034, China

Location

GSK Investigational Site

Changsha, 410013, China

Location

GSK Investigational Site

Chongqing, 400038, China

Location

GSK Investigational Site

Chongqing, China

Location

GSK Investigational Site

Guangzhou, 510120, China

Location

GSK Investigational Site

Nanchang, 330006, China

Location

GSK Investigational Site

Shanghai, 200433, China

Location

GSK Investigational Site

Gyeonggi-do, 410-719, South Korea

Location

GSK Investigational Site

Seoul, 130-709, South Korea

Location

GSK Investigational Site

Seoul, 130-872, South Korea

Location

GSK Investigational Site

Seoul, 380-704, South Korea

Location

GSK Investigational Site

Suwon, 442-723, South Korea

Location

Related Publications (1)

• Zhong N, Zheng J, Lee SH, Lipson DA, Du X, Wu S. Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study. Int J Chron Obstruct Pulmon Dis. 2020 Apr 17;15:809-819. doi: 10.2147/COPD.S215011. eCollection 2020.

  PMID: 32368027 BACKGROUND

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

GSKClinicalSupportHD@gsk.com

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2014
• First Posted: July 9, 2014
• Study Start: May 9, 2016
• Primary Completion: November 8, 2017
• Study Completion: November 8, 2017
• Last Updated: June 29, 2020
• Results First Posted: June 28, 2019

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CN (21); KR (5)