Impact of Inhaled PT003 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient (OSCIVARI)
Primary Purpose
Copd
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Formoterol-glycopyrronium co suspension (PT003)
Sponsored by
About this trial
This is an interventional treatment trial for Copd focused on measuring long acting bronchodilator, tidal breathing, variability, impulse oscillometry spirometry, plethysmography, dyspnea
Eligibility Criteria
Inclusion Criteria:
- Female or male subjects aged 40-75 years Documented COPD in stable condition FEV1 between 30 % and 70 % predicted (post bronchodilator) Significant dyspnea with a mMRC dyspnea scale
Exclusion Criteria:
- History or current diagnosis of asthma or ACO (asthma-COPD overlap syndrome)
- Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening
- Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters
- Severe renal impairment eGFR < 30
- Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated.
- Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant
Sites / Locations
- Hop Calmette Chu LilleRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PT003 treatment
Arm Description
Outcomes
Primary Outcome Measures
Analysis of tidal volume (VT) complexity (noise limit as main parameter )
Comparison of the noise limit between V2 baseline (pre-treatment) and V3 peak (2 hours +/- 30 min post dose).
Noise limit is a mathematical treatment of tidal breathing signal evaluating its complexity and no other description can be provided
Secondary Outcome Measures
change of frequency-tidal volume pattern
the inspiratory time (Ti, measured in second) , the expiratory time (Te,measured in second) and the respiratory frequency
Tidal volume Largest Lyapunov component (an indicator of the sensitivity of the system to initial conditions)
change of resistance at 5Hz , at 20 Hz
The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Resistance is complex measure that incorporates the lack of changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency.
All these measurements are expressed in the same unit (for resistance and reactance) and refer to oscillatory mechanics obtained by the same device. AX and resonant frequency are correlated to reactance.
Change of reactance
the fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency at 5Hz was used. Reactance is thought to reflect the elastic properties of the lung.
All these measurements are expressed in the same unit (for resistance and reactance) and refer to oscillatory mechanics obtained by the same device.
Change of AX and resonant frequency
Area under reactance curve (AX) and resonant frequency are correlated to reactance.
change of spirometry parameters
Spirometry : FEV1, FVC, FEV1/FVC
change in lung function as assessed through body plethysmography
Change from baseline to end of treatment in the following measures Total lung capacity (TLC) Residual volume (RV) Inspiratory capacity (IC) Functional residual capacity (FRC) All plethysmographic parameters shown here are lung volumes, expressed in liters, and are somewhat interrelated. For instance IC is TLC- FRC.There is no reason to separate these outcome measures
change of airway resistance (RAW) and specific airway conductance (sGAW).
sGaw is specific conductance, ie 1/resistance divided by the volume at which resistance was measured. These two parameters are always measured and used together.
All plethysmographic parameters shown here are lung volumes, expressed in liters, and are somewhat interrelated.
Visual Analogic Scale
Two VAS (± 100 mm ) will be used to evaluate changes (much worse-unchanged-much better) in dyspnea and chest tightness 2 hours after PT003 administration and at 4 weeks in through and post dose conditions
Likert scales
Likert scales (7 points) will assess changes in dyspnea and global health at visit 3 in comparison with pre treatment condition (V2).
BDI/TDI
The BDI/TDI is an instrument developed to provide a multidimensional measure of dyspnea in relation to activities of daily living. The Baseline Dyspnea Index (BDI) provides a measure of dyspnea at a single state, the baseline, and the Transitional Dyspnea Index (TDI) evaluates changes in dyspnea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference (MC
mMRC dyspnea scale
The Modified Medical Research Council (mMRC) dyspnea scale uses a simple grading system to assess a subject's level of dyspnea that consists of five statements about perceived breathlessness. It is an interviewer-administered ordinal scale on which subjects provide their dyspnea according to five grades of increasing severity (scores ranges from 0 (none) to 4 (very severe).
Modified Dyspnea Profile (MDP)
The MDP consists of 11 items evaluating both the sensory and affective dimensions of dyspnoea. One item (A1) assesses the unpleasantness of dyspnoea on a 0-10 visual numerical scale anchored by "neutral" (0) and "unbearable" (10). Five items assess the sensory dimension of dyspnoea, both in terms of quality and intensity (on a scale of 0-10). Five items assess the affective dimension of dyspnoea, also in terms of quality and intensity (on a scale of 0-10).
Full Information
NCT ID
NCT04087590
First Posted
July 10, 2019
Last Updated
August 18, 2022
Sponsor
University Hospital, Lille
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT04087590
Brief Title
Impact of Inhaled PT003 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient
Acronym
OSCIVARI
Official Title
Impact of Inhaled PT003 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 14, 2020 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Prospective, single-arm, open label, multicentre, phase II pilot study to evaluate the immediate and short term (one month) impact of a new long acting double bronchodilator on innovative parameters in stable and moderate to severe COPD patients.
Variability and complexity of resting tidal breathing
Oscillatory resistance and reactance of airways Tidal volume variability and complexity is decreased in airway obstruction and is expected to improve with a bronchodilator treatment, together with lung mechanics.
The relationship with changes in dyspnea and conventional pulmonary function tests is the second aim of study.
After baseline assessment of these parameters, clinical and lung function evaluation will be performed 2 hours post-drug (peak drug effects). Patients will continue treatment with PT003 for 4 weeks. On Day 30, the same clinical and lung function assessments will be performed pre (trough) and 2h-post dose in order to obtain after-treatment measurements.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Copd
Keywords
long acting bronchodilator, tidal breathing, variability, impulse oscillometry spirometry, plethysmography, dyspnea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PT003 treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Formoterol-glycopyrronium co suspension (PT003)
Intervention Description
Formoterol-glycopyrronium co suspension (PT003) in a Metered Dose Inhaler, 2 puffs twice daily
Primary Outcome Measure Information:
Title
Analysis of tidal volume (VT) complexity (noise limit as main parameter )
Description
Comparison of the noise limit between V2 baseline (pre-treatment) and V3 peak (2 hours +/- 30 min post dose).
Noise limit is a mathematical treatment of tidal breathing signal evaluating its complexity and no other description can be provided
Time Frame
at 1 month
Secondary Outcome Measure Information:
Title
change of frequency-tidal volume pattern
Description
the inspiratory time (Ti, measured in second) , the expiratory time (Te,measured in second) and the respiratory frequency
Time Frame
Baseline, at 1 month
Title
Tidal volume Largest Lyapunov component (an indicator of the sensitivity of the system to initial conditions)
Time Frame
Baseline, at 1 month
Title
change of resistance at 5Hz , at 20 Hz
Description
The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Resistance is complex measure that incorporates the lack of changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency.
All these measurements are expressed in the same unit (for resistance and reactance) and refer to oscillatory mechanics obtained by the same device. AX and resonant frequency are correlated to reactance.
Time Frame
Baseline, at 1 month
Title
Change of reactance
Description
the fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency at 5Hz was used. Reactance is thought to reflect the elastic properties of the lung.
All these measurements are expressed in the same unit (for resistance and reactance) and refer to oscillatory mechanics obtained by the same device.
Time Frame
Baseline, at 1 month
Title
Change of AX and resonant frequency
Description
Area under reactance curve (AX) and resonant frequency are correlated to reactance.
Time Frame
Baseline, at 1 month
Title
change of spirometry parameters
Description
Spirometry : FEV1, FVC, FEV1/FVC
Time Frame
at 1 month
Title
change in lung function as assessed through body plethysmography
Description
Change from baseline to end of treatment in the following measures Total lung capacity (TLC) Residual volume (RV) Inspiratory capacity (IC) Functional residual capacity (FRC) All plethysmographic parameters shown here are lung volumes, expressed in liters, and are somewhat interrelated. For instance IC is TLC- FRC.There is no reason to separate these outcome measures
Time Frame
Baseline, at 1 month
Title
change of airway resistance (RAW) and specific airway conductance (sGAW).
Description
sGaw is specific conductance, ie 1/resistance divided by the volume at which resistance was measured. These two parameters are always measured and used together.
All plethysmographic parameters shown here are lung volumes, expressed in liters, and are somewhat interrelated.
Time Frame
Baseline, at 1 month
Title
Visual Analogic Scale
Description
Two VAS (± 100 mm ) will be used to evaluate changes (much worse-unchanged-much better) in dyspnea and chest tightness 2 hours after PT003 administration and at 4 weeks in through and post dose conditions
Time Frame
Baseline, at 1 month
Title
Likert scales
Description
Likert scales (7 points) will assess changes in dyspnea and global health at visit 3 in comparison with pre treatment condition (V2).
Time Frame
Baseline, at 1 month
Title
BDI/TDI
Description
The BDI/TDI is an instrument developed to provide a multidimensional measure of dyspnea in relation to activities of daily living. The Baseline Dyspnea Index (BDI) provides a measure of dyspnea at a single state, the baseline, and the Transitional Dyspnea Index (TDI) evaluates changes in dyspnea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference (MC
Time Frame
Baseline, at 1 month
Title
mMRC dyspnea scale
Description
The Modified Medical Research Council (mMRC) dyspnea scale uses a simple grading system to assess a subject's level of dyspnea that consists of five statements about perceived breathlessness. It is an interviewer-administered ordinal scale on which subjects provide their dyspnea according to five grades of increasing severity (scores ranges from 0 (none) to 4 (very severe).
Time Frame
Baseline, at 1 month
Title
Modified Dyspnea Profile (MDP)
Description
The MDP consists of 11 items evaluating both the sensory and affective dimensions of dyspnoea. One item (A1) assesses the unpleasantness of dyspnoea on a 0-10 visual numerical scale anchored by "neutral" (0) and "unbearable" (10). Five items assess the sensory dimension of dyspnoea, both in terms of quality and intensity (on a scale of 0-10). Five items assess the affective dimension of dyspnoea, also in terms of quality and intensity (on a scale of 0-10).
Time Frame
Baseline, at 1 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female or male subjects aged 40-75 years Documented COPD in stable condition FEV1 between 30 % and 70 % predicted (post bronchodilator) Significant dyspnea with a mMRC dyspnea scale
Exclusion Criteria:
History or current diagnosis of asthma or ACO (asthma-COPD overlap syndrome)
Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening
Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters
Severe renal impairment eGFR < 30
Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated.
Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thierry PEREZ, MD,PhD
Phone
320445619
Ext
+33
Email
thierry.perez@chru-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry PEREZ, MD,PhD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hop Calmette Chu Lille
City
Lille
ZIP/Postal Code
59000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry PEREZ, MD,PhD
12. IPD Sharing Statement
Learn more about this trial
Impact of Inhaled PT003 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient
We'll reach out to this number within 24 hrs