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Comparative Study of Umeclidinium/Vilanterol (UMEC/VI) in a Fixed Dose Combination With Indacaterol Plus Tiotropium

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pulmonary Disease, Chronic Obstructive

Intervention: UMEC/VI (Drug); UMEC/VI matching placebo (Drug); Tiotropium (Drug); Tiotropium matching placebo (Drug); Indacaterol (Drug); Indacaterol matching placebo (Drug); Albuterol/salbutamol Metered Dose Inhaler (MDI) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Summary

This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI inhalation powder (62. 5/25 microgram [mcg] Once daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol plus tiotropium (150 mcg/18 mcg respectively QD) administered via individual inhalers over a treatment period of 12 weeks in participants with moderate to very severe Chronic Obstructive Pulmonary Disease (COPD). The purpose of this study is to demonstrate that UMEC/VI (delivered via ELLIPTA DPI), when used in symptomatic moderate to very severe COPD participants, is non-inferior to the combination of indacaterol (delivered via BREEZHALER® inhaler) plus tiotropium (delivered via HANDIHALER® inhaler) on measures of trough forced expiratory volume in one second (FEV1) after 12 weeks of treatment. Participants who met the eligibility criteria at screening (Visit 1) will complete a 5 to 7 day run in period prior to randomisation at Visit 2. Clinic visits will follow at day 2, week 2, week 4, week 8 and week 12 of treatment, plus week 12 + 1 day (Visits 3 to 8). The total duration of study participation will be approximately 14 weeks. ELLIPTA is a registered trademark of the GSK group of companies. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH & Co. KG. BREEZHALER is a registered trademark of Novartis AG.

Clinical Details

Official title: Study DB2116961, A Multicentre, Randomised, Blinded, Parallel Group Study to Compare UMEC/VI (Umeclidinium/Vilanterol) in a Fixed Dose Combination With Indacaterol Plus Tiotropium in Symptomatic Subjects With Moderate to Very Severe COPD

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Trough FEV1 on Treatment Day 85

Secondary outcome: Weighted mean (WM) FEV1 over 0-6 hours post dose at Week 12

Eligibility

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Type of subject: Outpatient

- Informed Consent: A signed and dated written informed consent prior to study

participation.

- Participants 40 years of age or older at Visit 1.

- Gender: Male or female participants. 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 Standard Operating Procedure (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)

- 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. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.

- Severity of Disease: A pre and post-albuterol/salbutamol Forced Expiratory Volume in

One Second/ Forced Vital Capacity (FEV1/ FVC) ratio of <0. 70 and a pre and post-albuterol/salbutamol FEV1 of <=70% predicted normal value at Visit 1, calculated using Quanjer reference equations.

- Dyspnoea: A score of >= 2 on the Modified Medical Research Council Dyspnoea Scale

(mMRC) at Visit 1.

- QT interval corrected (QTc) Criteria: QTc <450 milliseconds (msec) or QTc <480 msec

for patients with bundle branch block The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used as primary. The QTc should be based on single or averaged QTc values of triplicate Electrocardiogram (ECGs) obtained over a brief recording period.

- French participants: In France, a subject will be eligible for inclusion in this

study only if either affiliated to or a beneficiary of a social security category. 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. Allergy rhinitis is not exclusionary.

- Other Diseases/Abnormalities: Participants 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 or beta 2 agonist.

- Hospitalisation: Hospitalisation for COPD or pneumonia within 12 weeks prior to Visit

1.

- Lung Resection: Participants 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. Specific ECG findings that preclude subject eligibility will be listed in protocol The study investigator will determine the medical significance of any ECG abnormalities not listed.

- Screening labs: Significantly abnormal finding from clinical chemistry or haematology

tests at Visit 1 as determined by the study investigator.

- Medication 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: Depot corticosteroids (12 weeks); Oral or parenteral corticosteroids (6 weeks); Antibiotics (for lower respiratory tract infection) (6 weeks); Cytochrome P450 3A4 strong inhibitors ( 6 weeks); Long Acting Beta-Agonist (LABA)/ inhaled corticosteroids (ICS) combination products (e. g. fluticasone/salmeterol, mometasone, furoate/formoterol fumarate, budesonide/formoterol, fumarate), If LABA/ICS therapy is discontinued completely (30 days); If discontinuing LABA therapy and switching to ICS monotherapy (48 hours for salmeterol or formoterol, 14 days for Olodaterol, Indacaterol or, Vilanterol); Use of ICS at a dose >1000 mcg/day of fluticasone propionate or equivalent (30 days); Initiation or discontinuation of ICS use (30 days); Inhaled long acting beta2-agonists (LABA): Salmeterol, Formoterol (48 hours), Olodaterol, Indacaterol and Vilanterol (14 days); Long acting muscarinic antagonists (LAMA) (Tiotropium, Aclidinium, Glycopyrronium, Umeclidinium) (7 days); LABA/LAMA combination products (Whichever mono component has the longest washout); Roflumilast (14 days); Oral beta-agonists- Long-acting (48 hours), Short-acting(12 hours); Theophyllines (48 hours); Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours); Inhaled sodium cromoglycate or nedocromil sodium (24 hours); Inhaled short acting beta2-agonists (4 hours); Inhaled short-acting anticholinergic (short acting muscarinic antagonist [SAMA]) products eg ipratropium (4 hours); Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (SAMA/Short Acting beta2-agonists [SABA]) (4 hours); Any other investigational medication (30 days or within 5 drug half-lives)

- Oxygen: Use of Long Term Oxygen Therapy (LTOT).This is defined as oxygen therapy

prescribed for greater than 12 hours per 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 12 weeks prior to Visit 1. Participants 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.

- Participants who are pre-screen or screen failures cannot be re-screened.

Locations and Contacts

GSK Investigational Site, Buenos Aires C1424BSF, Argentina

GSK Investigational Site, Buenos Aires C1425BEN, Argentina

GSK Investigational Site, Ciudad Autónoma de Buenos Aires C1426ABP, Argentina

GSK Investigational Site, Mendoza 5500, Argentina

GSK Investigational Site, Mendoza M5500CCG, Argentina

GSK Investigational Site, San Miguel de Tucumán 4000, Argentina

GSK Investigational Site, Santiago 7500698, Chile

GSK Investigational Site, Haapsalu 90502, Estonia

GSK Investigational Site, Tallinn 10117, Estonia

GSK Investigational Site, Tallinn 10138, Estonia

GSK Investigational Site, Gières 38610, France

GSK Investigational Site, Nantes cedex 2 44277, France

GSK Investigational Site, Perpignan 66000, France

GSK Investigational Site, Reims Cedex 51092, France

GSK Investigational Site, Strasbourg cedex 67091, France

GSK Investigational Site, Tarbes Cedex 09 65013, France

GSK Investigational Site, Berlin 10367, Germany

GSK Investigational Site, Berlin 10787, Germany

GSK Investigational Site, Berlin 12203, Germany

GSK Investigational Site, Hamburg 20253, Germany

GSK Investigational Site, Hamburg 20354, Germany

GSK Investigational Site, Hamburg 22299, Germany

GSK Investigational Site, Balassagyarmat 2660, Hungary

GSK Investigational Site, Budaörs 2040, Hungary

GSK Investigational Site, Debrecen 4032, Hungary

GSK Investigational Site, Gödöllő 2100, Hungary

GSK Investigational Site, Nyíregyháza 4400, Hungary

GSK Investigational Site, Pécs 7635, Hungary

GSK Investigational Site, Szeged 6722, Hungary

GSK Investigational Site, Szikszó 3800, Hungary

GSK Investigational Site, Lima Lima 32, Peru

GSK Investigational Site, Lima Lima 18, Peru

GSK Investigational Site, Lima Lima 1, Peru

GSK Investigational Site, Lima Lima 14, Peru

GSK Investigational Site, Elblag 82-300, Poland

GSK Investigational Site, Krakow 31-024, Poland

GSK Investigational Site, Ostrow Wielkopolski 63-400, Poland

GSK Investigational Site, Piekary Slaskie 41-940, Poland

GSK Investigational Site, Slupsk 76-200, Poland

GSK Investigational Site, Sopot 81-741, Poland

GSK Investigational Site, Bucharest 020125, Romania

GSK Investigational Site, Bucharest 050159, Romania

GSK Investigational Site, Cluj Napoca 400371, Romania

GSK Investigational Site, Constanta 900002, Romania

GSK Investigational Site, Ramnicu Valcea 240564, Romania

GSK Investigational Site, Timisoara 300310, Romania

GSK Investigational Site, Timisoara 300579, Romania

GSK Investigational Site, Arkhangelsk 153000, Russian Federation

GSK Investigational Site, Ekaterinburg 620039, Russian Federation

GSK Investigational Site, Ekaterinburg 620149, Russian Federation

GSK Investigational Site, Irkutsk 664079, Russian Federation

GSK Investigational Site, Kazan 420015, Russian Federation

GSK Investigational Site, Moscow 115 478, Russian Federation

GSK Investigational Site, Moscow 125284, Russian Federation

GSK Investigational Site, Omsk 644112, Russian Federation

GSK Investigational Site, Orenburg 460040, Russian Federation

GSK Investigational Site, Perm 614068, Russian Federation

GSK Investigational Site, Saint Petesburg 195030, Russian Federation

GSK Investigational Site, St. Petersburg 194356, Russian Federation

GSK Investigational Site, St. Petersburg 198216, Russian Federation

GSK Investigational Site, Stavropol 355017, Russian Federation

GSK Investigational Site, Tomsk 634063, Russian Federation

GSK Investigational Site, Ulyanovsk 432063, Russian Federation

GSK Investigational Site, Bojnice 972 01, Slovakia

GSK Investigational Site, Humenne 066 01, Slovakia

GSK Investigational Site, Poprad 058 01, Slovakia

GSK Investigational Site, Spisska Nova Ves 052 01, Slovakia

GSK Investigational Site, Vrable 952 01, Slovakia

GSK Investigational Site, Ruedersdorf, Brandenburg 15562, Germany

GSK Investigational Site, Mar del Plata, Buenos Aires 7600, Argentina

GSK Investigational Site, Piacenza, Emilia-Romagna 29121, Italy

GSK Investigational Site, Pordenone, Friuli-Venezia-Giulia 33170, Italy

GSK Investigational Site, Frankfurt am Main, Hessen 60596, Germany

GSK Investigational Site, Frankfurt, Hessen 60389, Germany

GSK Investigational Site, Frankfurt, Hessen 60596, Germany

GSK Investigational Site, Lima 27, Lima Lima 27, Peru

GSK Investigational Site, Mantova, Lombardia 46100, Italy

GSK Investigational Site, Tradate (VA), Lombardia 21049, Italy

GSK Investigational Site, Schwerin, Mecklenburg-Vorpommern 19055, Germany

GSK Investigational Site, Novara, Piemonte 28100, Italy

GSK Investigational Site, Puente Alto - Santiago, Región Metro De Santiago 8207257, Chile

GSK Investigational Site, Santiago, Región Metro De Santiago 7500692, Chile

GSK Investigational Site, Santiago, Región Metro De Santiago 7510186, Chile

GSK Investigational Site, Magdeburg, Sachsen-Anhalt 39112, Germany

GSK Investigational Site, San Miguel de Tucuman, Tucumán 4000, Argentina

Additional Information

Starting date: October 2014
Last updated: August 20, 2015

Page last updated: August 23, 2015

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