Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
HANDIHALER, Dry Powder Inhaler, COPD, ELLIPTA, Inhaler preference attributes
Brief summary
This is a Phase IV multi-center, randomized, open-label, cross-over, placebo study in subjects with Chronic Obstructive Pulmonary Disease (COPD) to compare inhaler-specific preference attributes of two inhalers - ELLIPTA dry powder inhaler (DPI) and the HANDIHALER DPI. The primary objective of this study is to evaluate whether more subjects with COPD prefer the ELLIPTA inhaler to the HANDIHALER DPI based on the number of steps needed to take medication. All subjects will use the ELLIPTA inhaler and the HANDIHALER inhaler in the corresponding treatment periods based on the randomisation scheme, and at the end of 2 periods, complete the inhaler preference questionnaire. Subjects will self-administer the inhalation once daily for 5-9 days in each treatment period. This study will be placebo-only, and neither inhaler will contain active treatment. Subjects will continue their current COPD medication(s) as prescribed, and will follow up with their regular physician for their COPD healthcare during the study. Approximately 211 subjects will be enrolled in the study. ELLIPTA is a trademark of the GlaxoSmithKline group of companies. HANDIHALER is a trademark of Boehringer Ingelheim International GmbH.
Interventions
DRUGPlacebo ELLIPTA device
Placebo ELLIPTA is a DPI device containing powder for inhalation, to be inhaled orally once daily for 5-9 days. It contains two strips with 30 blisters per strip - one strip contains lactose monohydrate whereas the other strip contains lactose monohydrate blended with magnesium stearate.
DRUGPlacebo capsules for use in HANDIHALER device
Placebo capsules contain lactose monohydrate in the form of powder for inhalation, to be used with the HANDIHALER inhaler as an oral inhalation once daily for 5-9 days.
OTHERInhaler Preference Questionnaire Version 1
Consists of 5 questions to assess subjects' preference of device attributes and dosing regimens. The two versions of the questionnaire ask the same questions, but differ in the ordering of inhalers in their responses.
OTHERInhaler Preference Questionnaire Version 2
Consists of 5 questions to assess subjects' preference of device attributes and dosing regimens. The two versions of the questionnaire ask the same questions, but differ in the ordering of inhalers in their responses.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>=40 years of age at Visit 1. * Diagnosis of COPD with a documented history of COPD for at least 6 months. * Severity of Disease: Post albuterol/salbutamol 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. * Smoking History: 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 (for example, 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years). * Current COPD Therapy: 1. Currently receiving maintenance therapy with one or more long-acting bronchodilators, such as a long-acting muscarinic antagonist (LAMA; also known as a long-acting anti-cholinergic), long-acting beta 2-agonist (LABA), or inhaled corticosteroid (ICS)/LABA combination for the treatment of COPD. Subjects must be able to continue using their currently prescribed COPD maintenance inhaler therapy throughout the study and as needed short acting beta-adrenergic agonist (SABA) or short acting muscarinic antagonist (SAMA) for rescue use. 2. Has been on current maintenance COPD treatment for at least 4 weeks prior to Screening/Visit 1 and evaluated as unlikely to change COPD treatment within 4 weeks of Visit 1. * Males or * Females who are not pregnant or not planning a pregnancy during the study or not lactating. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions defined for this study. * Subject understands and is willing, able, and likely to comply with study procedures and restrictions. * Subject must be able to read, comprehend, and record information in English.
Exclusion criteria
* Asthma: Subjects with a current diagnosis of asthma. Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD. * Recent experience with the ELLIPTA inhaler: Subjects who used any ELLIPTA inhaler within 6 months (180 days) prior to Visit 1. * Recent experience with the HANDIHALER inhaler: Subjects who used any HANDIHALER inhaler within 6 months (180 days) prior to Visit 1. * Poorly controlled COPD: Subjects with symptoms of poorly controlled COPD such as: 1. Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician, in the 4 weeks prior to Visit 1. 2. Hospitalization due to acute worsening of COPD within 4 weeks of Visit 1. 3. Use of a total of 8 puffs/day or more of short-acting symptom relief medications such as albuterol and ipratropium for 2 consecutive days or any 3 days within 7 days immediately preceding Visit 1. 4. Changes in COPD symptoms and signs, suggesting worsening COPD health status at Visit 1. * Other Disease Abnormalities: 1. Subjects with suspected or evidence of oropharyngeal candidiasis. 2. 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 haematological abnormalities that are uncontrolled. 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 analysis if the disease/condition exacerbated during the study. 3. Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study. * Compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures, or unable to continue their current COPD medications. * Drug/alcohol abuse: Subjects with a known or suspected alcohol or drug abuse at Visit 1 which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirement. * Drug/Food Allergy: A history of hypersensitivity to any components of the study inhaler (for 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. * Investigational Product: Subjects who have received an investigational drug and/or medical device within 30 days of entry into this study (Screening/Visit 1), or within five drug half-lives of the investigational drug, whichever is longer. * Affiliation with Investigator's Site: A subject 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Preferring the Inhaler Based on the Number of Steps Needed to Take the COPD Medication | Up to 18 days | Preference between ELLIPTA inhaler and Handihaler based on the number of steps needed to take the medication was assessed by the inhaler preference questionnaire at Visit 3 or Early Withdrawal (EW) visit. The responses were analyzed using a Cochran-Mantel-Haenszel test, adjusted for study inhaler use sequence and preference questionnaire version. The analysis was performed on the Modified Intent-to-treat (ITT) Population comprised of all participants in the ITT Population (comprised all randomized participants who received 1 dose of at least 1 study inhaler) who completed at least one question from the 5 preference questions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Preferring the Inhaler Based on How Easy it Was to Tell How Many Doses Were Left | Up to 18 days | Preference between ELLIPTA inhaler and Handihaler based on how easy it was to tell how many doses were left was assessed by the inhaler preference questionnaire at Visit 3 or EW visit. The responses were analyzed using a Cochran-Mantel-Haenszel test, adjusted for study inhaler use sequence and preference questionnaire version. |
| Percentage of Participants Preferring the Inhaler Based on the Size of the Inhaler | Up to 18 days | Preference between ELLIPTA inhaler and HandiHaler based on the size of the inhaler was assessed by the inhaler preference questionnaire at Visit 3 or EW visit. The responses were analyzed using a Cochran-Mantel-Haenszel test, adjusted for study inhaler use sequence and preference questionnaire version. |
Countries
United States
Participant flow
Recruitment details
Eligible participants who met the inclusion criteria at screening were randomized to use ELLIPTA inhaler and Handihaler inhaler in a crossover manner at Visit 1 and Visit 2 once daily for 5-9 days. At Visit 3, participants were asked to complete the inhaler preference questionnaire.
Pre-assignment details
A total of 227 participants with diagnosis and documented history of chronic obstructive pulmonary disease (COPD) were screened for this open-label, cross-over study, of which 13 were screen failures, 2 were randomized by error and did not receive treatment and 212 participants entered the study treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| ELLIPTA and HandiHaler Participants were randomized to receive placebo using ELLIPTA inhaler and HandiHaler inhaler once daily for 5-9 days each in a crossover manner along with their routine COPD medication. | 212 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | ELLIPTA and HandiHaler |
|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 9.15 |
| Race/Ethnicity, Customized Race/Ethnicity African American/African Heritage | 22 Participants |
| Race/Ethnicity, Customized Race/Ethnicity American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian - Japanese Heritage | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White - Arabic/North African Heritage | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White - White/Caucasian/European Heritage | 187 Participants |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 208 | 0 / 212 |
| serious Total, serious adverse events | 0 / 208 | 2 / 212 |
Outcome results
Primary
Percentage of Participants Preferring the Inhaler Based on the Number of Steps Needed to Take the COPD Medication
Preference between ELLIPTA inhaler and Handihaler based on the number of steps needed to take the medication was assessed by the inhaler preference questionnaire at Visit 3 or Early Withdrawal (EW) visit. The responses were analyzed using a Cochran-Mantel-Haenszel test, adjusted for study inhaler use sequence and preference questionnaire version. The analysis was performed on the Modified Intent-to-treat (ITT) Population comprised of all participants in the ITT Population (comprised all randomized participants who received 1 dose of at least 1 study inhaler) who completed at least one question from the 5 preference questions.
Time frame: Up to 18 days
Population: Modified ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on the Number of Steps Needed to Take the COPD Medication | ELLIPTA inhaler | 73 Percentage of participants |
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on the Number of Steps Needed to Take the COPD Medication | HandiHaler | 20 Percentage of participants |
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on the Number of Steps Needed to Take the COPD Medication | No preference | 7 Percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Preferring the Inhaler Based on How Easy it Was to Tell How Many Doses Were Left
Preference between ELLIPTA inhaler and Handihaler based on how easy it was to tell how many doses were left was assessed by the inhaler preference questionnaire at Visit 3 or EW visit. The responses were analyzed using a Cochran-Mantel-Haenszel test, adjusted for study inhaler use sequence and preference questionnaire version.
Time frame: Up to 18 days
Population: Modified ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on How Easy it Was to Tell How Many Doses Were Left | ELLIPTA inhaler | 70 Percentage of participants |
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on How Easy it Was to Tell How Many Doses Were Left | HandiHaler | 18 Percentage of participants |
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on How Easy it Was to Tell How Many Doses Were Left | No preference | 12 Percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Preferring the Inhaler Based on the Size of the Inhaler
Preference between ELLIPTA inhaler and HandiHaler based on the size of the inhaler was assessed by the inhaler preference questionnaire at Visit 3 or EW visit. The responses were analyzed using a Cochran-Mantel-Haenszel test, adjusted for study inhaler use sequence and preference questionnaire version.
Time frame: Up to 18 days
Population: Modified ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on the Size of the Inhaler | ELLIPTA inhaler | 52 Percentage of participants |
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on the Size of the Inhaler | HandiHaler | 25 Percentage of participants |
| ELLIPTA and HandiHaler | Percentage of Participants Preferring the Inhaler Based on the Size of the Inhaler | No preference | 24 Percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel