COPD
Conditions
Keywords
DPI, PIF, FEV1
Brief summary
The purpose of the study is to determine whether PIF is clinically important when using the Ellipta DPI device. In addition, the study will validate the best/most clinically appropriate way to perform a PIF maneuver, to determine the testing capabilities of the preferred PIF maneuver and to relate this PIF measurement to meaningful clinical outcomes in COPD patients
Detailed description
Study Design and Methods Rationale * The expected FEV1 response to a bronchodilator is uncertain as multiple factors influence this measure, including severity of disease, day to day variability, varying reversibility in COPD patients, the delivery of the drug to a patient and the effectiveness of the medication delivered. Thus, the measurement of an acute bronchodilator response after delivering a long acting bronchodilator may not identify whether a medication has been effectively delivered to a patient. * However, if a long acting bronchodilator has not been effectively delivered to the lung, then subsequent delivery of a short acting bronchodilator should produce a significant additional bronchodilator response. On the other hand, if a long acting bronchodilator has been effectively delivered to the lung, then subsequent delivery of a short acting bronchodilator should not produce any further significant bronchodilation. * Based on this rationale, comparison of the acute bronchodilator response to a short acting bronchodilator after receiving a long acting should identify whether drug delivery is ineffective in a selected patient population, irrespective of baseline FEV1 and of any partial response to the long acting bronchodilator. Comparison of the short acting bronchodilator measurement between patient groups with differing PIF thresholds should identify whether PIF has an impact of drug delivery of a long acting bronchodilator via a DPI. * Open label design comparing the acute bronchodilator response after delivery of a long acting bronchodilator via Ellipta DPI in patients with normal, suboptimal and minimal PIF.
Interventions
Administration of Trelegy in all patients
DRUGVentolin 90Mcg/Actuation Inhalation Aerosol
2 hours after the administration of Trelegy, administer Ventolin in all patients
Sponsors
GlaxoSmithKline
Pulmonary Research Institute of Southeast Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label comparative design
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* smoking history \>10 pack years * pre-bronchodilator FEV1 \<60% predicted * post-bronchodilator FEV1/FVC \<70% * female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: * not a woman of childbearing potential OR * agree to follow the contraceptive guidance during the treatment period and until the safety follow-up contact after the last dose of study treatment * stratification requiring at least 1/3 of patients having a PIF of \< 60L/min (AM pre-dose based on using the level 2 InCheck Dial resistance setting with a sharp maximal effort starting after exhaling fully)
Exclusion criteria
* any subject with unstable disease, including * COPD exacerbation in the last 6 weeks * upper respiratory tract in in the last 4 weeks * COPD or upper respiratory tract infection during run-in (subjects may be re-screened x 1 when stable after an acute event) * pulmonary disease other than COPD * any lung resection * unstable cardiac conditions (at the discretion of the investigator) * other unstable medical conditions (at the discretion of the investigator)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DPI Responder Analysis in Patients With Suboptimal PIF (<60 L/Min) | 2 weeks | Outcome = the number of subject test days (2 test days per subject) meeting responder criteria defined as: DPI Responder - a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Partial Responder a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy® Ellipta DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Failure - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) Irreversible - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DPI Responder Analysis in Patients With Reduced PIF (<45 L/Min) | 2 weeks | Outcome = the number of subject test days (2 test days per subject) meeting responder criteria defined as: DPI Responder - a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Partial Responder a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy® Ellipta DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Failure - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) Irreversible - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) |
| PIF Measurement Techniques | Baseline on day of testing | PIF value (L/min) based on different PIF measurement techniques |
Countries
United States
Participant flow
Recruitment details
Severe/very severe COPD patients in stable condition stratified to insure that at least 12 of 30 subjects had a suboptimal peak inspiratory flow (PIF \<60L/min)
Pre-assignment details
Enrollment, run-in on current maintenance therapy followed by testing, conversion of maintenance therapy to Trelegy Ellipta therapy for 2 weeks followed by testing
Participants by arm
| Arm | Count |
|---|---|
| Open Label Treatment All subjects receive Trelegy and Ventolin for 2 weeks
Trelegy Ellipta 100/62.5/25Mcg Inh 30D: Administration of Trelegy in all patients
Ventolin 90Mcg/Actuation Inhalation Aerosol: 2 hours after the administration of Trelegy, administer Ventolin in all patients | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Exclusion criteria screen failure | 12 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Open Label Treatment | — |
|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 7 | — |
| CAT score ≥10 | 30 Participants | — |
| CAT score ≥15 | 28 Participants | — |
| History of 2 moderate/1 severe exacerbation | 9 Participants | — |
| History of severe exacearbtion | 8 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 13 Participants | — |
| Sex: Female, Male Male | 17 Participants | — |
| Using triple therapy at baseline | 18 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 0 / 45 |
| serious Total, serious adverse events | 0 / 45 |
Outcome results
Primary
DPI Responder Analysis in Patients With Suboptimal PIF (<60 L/Min)
Outcome = the number of subject test days (2 test days per subject) meeting responder criteria defined as: DPI Responder - a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Partial Responder a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy® Ellipta DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Failure - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) Irreversible - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy)
Time frame: 2 weeks
Population: Number of subject test days (2 per subject) with DPI Failure based on baseline PIF \<60 L/min or \>60 L/min
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suboptimal PIF | DPI Responder Analysis in Patients With Suboptimal PIF (<60 L/Min) | 2 Number of subject test days |
| Normal PIF | DPI Responder Analysis in Patients With Suboptimal PIF (<60 L/Min) | 1 Number of subject test days |
Comparison: Data outcome reported was the number and percentage of subject test days with DPI Failure in subjects in suboptimal PIF (\<60 L/min) versus normal PIF subjects. Statistical analysis performed was a comparison between rates of DPI Failure in the 2 groups.p-value: 0.33Chi-squared
Secondary
DPI Responder Analysis in Patients With Reduced PIF (<45 L/Min)
Outcome = the number of subject test days (2 test days per subject) meeting responder criteria defined as: DPI Responder - a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Partial Responder a positive (\>50 ml) peak FEV1 response 2 hours after Trelegy® Ellipta DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Failure - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a positive (\>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) Irreversible - a negative (\<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (\<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy)
Time frame: 2 weeks
Population: Number of subject test days (2 per subject) with DPI Failure based on baseline PIF \<45 L/min or \>45 L/min
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suboptimal PIF | DPI Responder Analysis in Patients With Reduced PIF (<45 L/Min) | 2 Number of subject test days |
| Normal PIF | DPI Responder Analysis in Patients With Reduced PIF (<45 L/Min) | 1 Number of subject test days |
Comparison: Data outcome reported was the number and percentage of subject test days with DPI Failure in subjects in suboptimal PIF (\<60 L/min) versus normal PIF subjects. Statistical analysis performed was a comparison between rates of DPI Failure in the 2 groups.p-value: 0.04Chi-squared
Secondary
PIF Measurement Techniques
PIF value (L/min) based on different PIF measurement techniques
Time frame: Baseline on day of testing
Population: All subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suboptimal PIF | PIF Measurement Techniques | 52 L/min | Standard Deviation 17 |
| Normal PIF | PIF Measurement Techniques | 53 L/min | Standard Deviation 25 |
| Instructed PIF | PIF Measurement Techniques | 70 L/min | Standard Deviation 18 |
| Encouraged PIF | PIF Measurement Techniques | 74 L/min | Standard Deviation 18 |
| Spiro PIF | PIF Measurement Techniques | 137 L/min | Standard Deviation 67 |