Last updated: 11/07/2018 11:15:41
Comparative Study of Umeclidinium/Vilanterol (UMEC/VI) in a Fixed Dose Combination With Indacaterol Plus Tiotropium
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in trough forced expiratory volume in one second (FEV1) on Treatment Day 85 (Visit 8)
Timeframe: Baseline (BL) and Day 85
Secondary outcomes:
Change from Baseline in weighted mean (WM) FEV1 over 0-6 hour post-dose at Day 84
Timeframe: Baseline and Day 84
Interventions:
Enrollment:
967
Primary completion date:
2015-04-05
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Kalberg C, O'Dell D, Galkin D, Newlands A, Fahy WA. Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial. Drugs R D. 2016;16(2):217-227
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
indacaterol, tiotropium bromide, umeclidinium bromide, umeclidinium bromide/vilanterol, vilanterol
Collaborators
Not applicable
Study date(s)
October 2014 to May 2015
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
40+ years
Accepts healthy volunteers
No
- Type of subject: Outpatient
- Informed Consent: A signed and dated written informed consent prior to study participation.
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- Asthma: A current diagnosis of asthma.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
San Miguel de Tucumán, Argentina, 4000
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, C1424BSF
Status
Study Complete
Location
GSK Investigational Site
Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
Status
Study Complete
Location
GSK Investigational Site
Pordenone, Friuli-Venezia-Giulia, Italy, 33170
Status
Study Complete
Location
GSK Investigational Site
San Miguel de Tucuman, Tucumán, Argentina, 4000
Status
Study Complete
Location
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7510186
Status
Study Complete
Location
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
Status
Study Complete
Location
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
Status
Study Complete
Location
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60596
Status
Study Complete
Location
GSK Investigational Site
Piacenza, Emilia-Romagna, Italy, 29121
Status
Study Complete
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2015-04-05
Actual study completion date
2015-04-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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