Clinical trial NCT03227445: Comparative Study of ELLIPTA Dry Powder Inhaler (DPI) Versus DISKUS DPI Used With HandiHaler DPI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Randomized, Open-label, Cross-over, Placebo Inhaler Study to Evaluate the Correct Use of ELLIPTA™ Dry Powder Inhaler (DPI) Compared to DISKUS™ DPI Used in Combination With HandiHaler DPI in Participants With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: DISKUS
HandiHaler
COPD
Placebo
Cross-over
Dry powder inhaler
ELLIPTA
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-07-24
Enrollment: 240
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Subjects will be randomized to receive a placebo ELLIPTA inhaler QD or a placebo DISKUS BID with placebo HandiHaler QD inhaler at Visit 1 and Visit 2 in a cross-over manner followed by Preference Questionnaire 1 or 2
Primary purpose: TREATMENT

Brief summary: This randomized, cross over study aims to find out the benefits of delivering triple therapy using a single ELLIPTA® DPI (fixed-dose combination triple therapy) versus delivering triple therapy using two different types of inhalers (open triple therapy) including DISKUS® with HandiHaler® to subjects with COPD. Correct inhaler use, critical errors and performance attributes will also be assessed. Approximately 240 subjects with COPD will be randomized in the study. The study will be conducted in 3 visits and will be completed in approximately 56 days. At Visit 1 (Day 1) and Visit 2 (Day 28) subjects will be randomized to receive a placebo ELLIPTA inhaler once daily (QD) or a placebo DISKUS twice daily (BID) with placebo HandiHaler QD inhaler in 1:1 ratio in a cross-over manner for the study period (28 days for each period). At Visit 3 (Day 56), subjects will be asked to complete preference questionnaire 1 or 2. There will be no active treatment and subjects will continue to take their own prescribed COPD maintenance and rescue medication during the entire study period. ELLIPTA and DISKUS are the registered trademarks of GlaxoSmithKline group of companies. HandiHaler is the registered trademark of Boehringer Ingelheim group of companies.


Eligibility criteria: Inclusion Criteria:

* Subjects must be capable of giving signed informed consent.
* Subjects must have a diagnosis of COPD with a documented history of COPD for at least 12 months, in accordance with the definition by the American Thoracic Society/European Respiratory Society.
* Subjects must be 40 years of age inclusive, at the time of signing the informed consent.
* Male or female subjects will be included. Females must not be pregnant or planning pregnancy during the study or not lactating.
* Subjects must have a documented post albuterol forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ratio \<0.70 and FEV1 \<=70% of predicted obtained within two years of Visit 1.
* Current or former (defined as subjects who have quit smoking for at least 3 months prior to Screening/Visit 1) cigarette smokers with a \> 10 pack-year smoking history \[Number of pack-years = (number of cigarettes per day/20) x number of years smoked (example, 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years\].
* All subjects should be currently receiving maintenance treatment for COPD for at least 4 weeks prior to Randomization/Visit 1 and evaluated as unlikely to change COPD treatment within 4 weeks of Visit 1.
* All subjects should be able to stay on their prescribed maintenance COPD inhaler (s) without change throughout the entire treatment period.
* Subjects must be able to read, comprehend, and record information in English.

Exclusion Criteria:

* Subjects must not have a current diagnosis of asthma.
* Subjects must not have used the ELLIPTA, DISKUS, or HandiHaler inhalers in the 12 months prior to Visit 1.
* Subjects must not be receiving their current COPD medications with the ELLIPTA, DISKUS, or HandiHaler inhalers.
* Subjects must not be receiving only inhaled short-acting beta-adrenergic agonists, i.e., albuterol as their daily COPD therapy (as needed or regularly scheduled).
* Subjects must not have experienced more than 1 COPD exacerbation which required hospitalization in the 12 months prior to Visit 1.
* Subjects must not have a known or suspected history of alcohol or drug abuse within the last 2 years.
* Subjects must not have a history of hypersensitivity to any component of the study inhalers (example, lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates participation will also be excluded.
* Subjects with other respiratory disorders, including active tuberculosis, active lung cancer, sarcoidosis, lung fibrosis, pulmonary hypertension, or pulmonary disease (including but not confined to asthma, bronchiectasis with the need for treatment, cystic fibrosis, and bronchopulmonary dysplasia), interstitial lung diseases or other active pulmonary diseases.
* Subjects with historical, or current evidence of clinically significant or rapidly progressing or unstable cardiovascular, neurological, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or which would affect the analysis if the disease/condition exacerbated during the study will be excluded.
* Subjects with history of psychiatric disease, intellectual impairment, poor motivation or other conditions that will limit the validity of informed consent to participate in the study will be excluded.
* Subjects at risk of non-compliance, or unable to comply with the study procedures, or unable to continue their current medications.
* Subjects who have received an investigational drug and/or medical device/inhaler within 30 days of entry into this study (Screening/Visit 1), or within five drug half-lives of the investigational drug, whichever is longer.
* Subjects will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub investigator, study coordinator, or employee of the participating investigator.

Primary outcomes:
measure: Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Supplementary Estimand: Composite)
timeFrame: Up to Day 56
measure: Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase(Supplementary Estimand: Composite)
timeFrame: Up to Day 56
Secondary outcomes:
measure: Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Number of Errors Per Participant for Each Treatment Group After 28 Days of Use (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Change in Errors Per Participant for Each Treatment Group After 28 Days of Use
timeFrame: Day 1 and Day 28 of each treatment group
measure: Number of Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Change in Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use
timeFrame: Day 1 and Day 28 of each treatment group
measure: Number of Participants With Zero Critical Errors After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical)
timeFrame: Up to Day 56
measure: Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Supplementary Estimand: Composite)
timeFrame: Up to Day 56
Other outcomes:
Locations:
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Natchitoches
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Saint Charles
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Gastonia
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Monroe
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Mooresville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Anderson
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Rock Hill
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kerwin EM, Spangenthal S, Zvarich M, Millar V, Jain R, Collison K, Sharma R. ELLIPTA Versus DISKUS plus HandiHaler in COPD: A Randomized, Open-Label, Crossover Study in a Clinical Trial Setting. Chronic Obstr Pulm Dis. 2020 Apr;7(2):118-129. doi: 10.15326/jcopdf.7.2.2019.0153.