The Purpose of This Study is to Evaluate the Spirometric Effect (Trough FEV1) of Umeclidinium/Vilanterol 62.5/25 mcg Once Daily Compared With Tiotriopium 18 mcg Once Daily Over a 24-week Treatment Period in Subjects With COPD

NCT ID: NCT01777334

Last Updated: 2018-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 905 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-23
• Study Completion Date: 2013-09-24

Brief Summary

The purpose of this 24 week study is to evaluate the spirometric lung function effect (trough FEV1) of Umeclidinium/Vilanterol 62.5/25 once daily compared to Tiotropium 18 mcg once daily along with safety assessments in subjects with COPD.

Detailed Description

This is a Phase IIIb multicenter, randomized, double-dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI Inhalation Powder (62.5/25 mcg) when administered once-daily via a novel dry powder inhaler (DPI) compared with tiotropium (18 mcg) administered once-daily via the HandiHaler over a treatment period of 24 weeks in subjects with COPD. Eligible subjects will be randomized 1:1 to UMEC/VI Inhalation Powder (62.5/25 mcg), or tiotropium (18 mcg) for 24 weeks.

There will be a total of 10 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 7- to 10-day run-in period followed by a 24-week treatment period. Clinic visits will be at Screening, Randomization (Day 1), Day 2 and after 4, 8, 12, 16, 20 and 24 weeks, and 1 day after the Week 24 visit (Visit 1 to Visit 10, respectively). Additionally a safety Follow-Up assessment will be conducted either by phone call or clinic visit where required approximately 7 days after the end of the study treatment (Visit 10 or Early Withdrawal, if applicable). The total duration of subject participation, including the Follow-Up will be approximately 26 weeks.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Umeclidinium/Vilanterol

Long-acting muscarinic antagonist (LAMA)/Long-acting Beta agonist (LABA)

Group Type: EXPERIMENTAL

Umeclidinium/Vilanterol 62.5/25 mcg

Intervention Type: DRUG

Inhalation Powder

Tiotropium

Long-acting muscarinic antagonist (LAMA)

Group Type: ACTIVE_COMPARATOR

Tiotropium 18 mcg

Intervention Type: DRUG

Inhalation Powder

Interventions

Umeclidinium/Vilanterol 62.5/25 mcg

Inhalation Powder

Intervention Type: DRUG

Tiotropium 18 mcg

Inhalation Powder

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Type of subject: 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 (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)

• COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004].
• 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

• Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a pre and post-albuterol/salbutamol FEV1 of FEV1 of <=70% of predicted normal values calculated using NHANES III reference equations at Visit 1 [Hankinson, 1999; Hankinson, 2010].
• Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1.

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 conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
• 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.
• 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.
• 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).
• 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 electrocardiogram (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 4. The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 4.
• Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
• Use of certain medications according to defined time intervals prior to Screening (Visit 1).
• 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., albuterol/salbutamol) 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.
• Previous use of study drug: Previous participation in DB2113360 or DB2113374.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Riverside, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

DeLand, Florida, United States

GSK Investigational Site

Panama City, Florida, United States

GSK Investigational Site

Coeur d'Alene, Idaho, United States

GSK Investigational Site

Saint Charles, Missouri, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Easley, South Carolina, United States

GSK Investigational Site

Gaffney, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Rock Hill, South Carolina, United States

GSK Investigational Site

Spartanburg, South Carolina, United States

GSK Investigational Site

Union, South Carolina, United States

GSK Investigational Site

Johnson City, Tennessee, United States

GSK Investigational Site

Ciudad Autnónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Dimitrovgrad, , Bulgaria

GSK Investigational Site

Pleven, , Bulgaria

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Rousse, , Bulgaria

GSK Investigational Site

Stara Zagora, , Bulgaria

GSK Investigational Site

Troyan Municipality, , Bulgaria

GSK Investigational Site

Varna, , Bulgaria

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Moncton, New Brunswick, Canada

GSK Investigational Site

Burlington, Ontario, Canada

GSK Investigational Site

Hamilton, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Saint-Charles-Borromée, Quebec, Canada

GSK Investigational Site

Sherbrooke, Quebec, Canada

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Neu-Isenburg, Hesse, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Geesthacht, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Balassagyarmat, , Hungary

GSK Investigational Site

Budaörs, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Gödöllő, , Hungary

GSK Investigational Site

Nyíregyháza, , Hungary

GSK Investigational Site

Szikszó, , Hungary

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Codlea, , Romania

GSK Investigational Site

Deva, , Romania

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Belgorod, , Russia

GSK Investigational Site

Krasnodar, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Pyatigorsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Mérida (Badajoz), , Spain

GSK Investigational Site

Salt (gerona), , Spain

GSK Investigational Site

Valencia, , Spain

Countries

United States; Argentina; Bulgaria; Canada; Germany; Hungary; Romania; Russia; Spain

References

Maleki-Yazdi MR, Singh D, Anzueto A, Tombs L, Fahy WA, Naya I. Assessing Short-term Deterioration in Maintenance-naive Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials. Adv Ther. 2017 Jan;33(12):2188-2199. doi: 10.1007/s12325-016-0430-6. Epub 2016 Oct 28.

Reference Type: DERIVED

PMID: 27796912 (View on PubMed)

Study Documents

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

117115

Identifier Type: -

Identifier Source: org_study_id