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Lack of recruitment
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This is a randomized, double-blind, placebo-controlled, single-center, chronic-dosing (7 days), two-period, two-treatment, cross-over study to evaluate the treatment effect of PT003 compared with that of Placebo MDI on Cardiovascular Hemodynamics following chronic-dosing (7 days) in subjects with moderate to severe COPD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GFF MDI (PT003) | Experimental | Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) |
|
| Placebo MDI | Placebo Comparator | Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GFF MDI (PT003) | Drug | Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVi) at 2-3 Hours Post-dose on Day 8 | Assessment of right ventricular (RV) volume was performed using magnetic resonance imaging (MRI) using RV end diastolic volume (RVEDV), 2-3 hours after dosing on Day 8 of each treatment period. RVEDV was normalized to body surface area (BSA) to provide the indexed counterpart (RVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Aortic Left Ventricular Stroke Volume (LVSV) at 2-3 Hours Post-dose on Day 8 | Assessment of LVSV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Colin Reisner, MD | Pearl Therapeutics | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Birmingham | Alabama | 35294 | United States |
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| Label | URL |
|---|---|
| Related Info | View source |
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AstraZeneca's policy is to share data with researchers if the request is in scope of our policy. The policy and additional information can be found on astrazenecaclinicaltrials.com.
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Subjects were randomly assigned, in a 1:1 ratio, to receive either Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) then Placebo MDI or Placebo MDI then GFF MDI in two 7-day treatment periods, separated by a washout period of between 7 and 21 days.
Subjects with moderate to severe chronic obstructive pulmonary disease (COPD) were enrolled into this 2-period, 2-treatment, crossover study from 09 December 2016. The study was terminated early on 20 June 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | GFF MDI, Then Placebo MDI | Subjects first received GFF MDI (PT003) 14.4/9.6 micrograms (μg) as 2 inhalations twice daily (BID) for 7 days in treatment period 1. After a washout period, subjects then received Placebo MDI as 2 inhalations BID for 7 days in treatment period 2. |
| FG001 | Placebo MDI, Then GFF MDI | Subjects first received Placebo MDI as 2 inhalations BID for 7 days in treatment period 1. After a washout period, subjects then received GFF MDI 14.4/9.6 μg as 2 inhalations BID for 7 days in treatment period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Washout Period |
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| Treatment Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Randomized Subjects | All subjects randomized to receive treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVi) at 2-3 Hours Post-dose on Day 8 | Assessment of right ventricular (RV) volume was performed using magnetic resonance imaging (MRI) using RV end diastolic volume (RVEDV), 2-3 hours after dosing on Day 8 of each treatment period. RVEDV was normalized to body surface area (BSA) to provide the indexed counterpart (RVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm^3/m^2 | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
|
Adverse events were collected from screening, throughout the treatment periods until the follow-up visit 14±2 days from the last study treatment administration. Overall timeframe of up to a maximum of 12 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GFF MDI | GFF MDI (PT003) 14.4/9.6 μg was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
This study was terminated early on 20 June 2018 as target enrollment numbers were not met.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | Pearl Therapeutics Inc. | +1 302 885 1180 | ClinicalTrialTransparency@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 26, 2016 | Aug 12, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| Placebo MDI | Drug | Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol |
|
| Change From Baseline in Right Ventricular Stroke Volume (RVSV) at 2-3 Hours Post-dose on Day 8 | Assessment of RVSV, phase contrast from pulmonic valve, was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Pulmonary Artery Velocity at 2-3 Hours Post-dose on Day 8 | Assessment of Pulmonary Artery Velocity was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi) at 2-3 Hours Post-dose on Day 8 | Assessment of left ventricular (LV) volume was performed using MRI using LV end diastolic volume (LVEDV), 2-3 hours after dosing of Day 8 of each treatment period. LVEDV was normalized to BSA to provide the indexed counterpart (LVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Cardiac Output at 2-3 Hours Post-dose on Day 8 | Assessment of cardiac output was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Pulmonary Vascular Resistance (PVR) at 30 and 60 Minutes Post-dose on Day 8 | Assessment of PVR was performed by impedance cardiography at 30 and 60 minutes after dosing on Day 8 of each treatment period. Baseline for was defined as the average of the subject values obtained pre-dose on Day 1 of each treatment period. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Pulmonary Artery/Aortic Diameter Ratio (PA:A) at 2-3 Hours Post-dose on Day 8 | Assessment of PA:A was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Left Atrial End Diastolic Volume (LAEDV) at 2-3 Hours Post-dose on Day 8 | Assessment of LAEDV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Left Atrial End Systolic Volume (LAESV) at 2-3 Hours Post-dose on Day 8 | Assessment of LAESV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Left Atrial Ejection Fraction (LAEF) at 2-3 Hours Post-dose on Day 8 | Assessment of LAEF was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVi) at 2-3 Hours Post-dose on Day 8 | Assessment of LV volume was performed using MRI using LV end systolic volume (LVESV), 2-3 hours after dosing on Day 8 of each treatment period. LVESV was normalized to BSA to provide the indexed counterpart (LVESVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Right Ventricular End Systolic Volume Index (RVESVi) at 2-3 Hours Post-dose on Day 8 | Assessment of RV volume was performed using MRI using RV end systolic volume (RVESV), 2-3 hours after dosing on Day 8 of each treatment period. RVESV was normalized to BSA to provide the indexed counterpart (RVESVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Pulsatility Index Aorta (PIAo) at 2-3 Hours Post-dose on Day 8 | Assessment of PIAo was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
| Change From Baseline in Pulmonary Artery Pulsatility Index (PAPi) at 2-3 Hours Post-dose on Day 8 | Assessment of PAPi was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Placebo MDI |
Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2. |
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| Secondary | Change From Baseline in Aortic Left Ventricular Stroke Volume (LVSV) at 2-3 Hours Post-dose on Day 8 | Assessment of LVSV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm^3 | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Right Ventricular Stroke Volume (RVSV) at 2-3 Hours Post-dose on Day 8 | Assessment of RVSV, phase contrast from pulmonic valve, was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm^3 | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Pulmonary Artery Velocity at 2-3 Hours Post-dose on Day 8 | Assessment of Pulmonary Artery Velocity was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm/second | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi) at 2-3 Hours Post-dose on Day 8 | Assessment of left ventricular (LV) volume was performed using MRI using LV end diastolic volume (LVEDV), 2-3 hours after dosing of Day 8 of each treatment period. LVEDV was normalized to BSA to provide the indexed counterpart (LVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm^3/m^2 | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Cardiac Output at 2-3 Hours Post-dose on Day 8 | Assessment of cardiac output was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | Liters/minute | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Pulmonary Vascular Resistance (PVR) at 30 and 60 Minutes Post-dose on Day 8 | Assessment of PVR was performed by impedance cardiography at 30 and 60 minutes after dosing on Day 8 of each treatment period. Baseline for was defined as the average of the subject values obtained pre-dose on Day 1 of each treatment period. | Due to early termination of the study, data for this endpoint were not collected. | Posted | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Pulmonary Artery/Aortic Diameter Ratio (PA:A) at 2-3 Hours Post-dose on Day 8 | Assessment of PA:A was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects | Posted | Mean | Standard Deviation | ratio | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Left Atrial End Diastolic Volume (LAEDV) at 2-3 Hours Post-dose on Day 8 | Assessment of LAEDV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Due to early termination of the study, data for this endpoint were not collected. | Posted | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Left Atrial End Systolic Volume (LAESV) at 2-3 Hours Post-dose on Day 8 | Assessment of LAESV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Due to early termination of the study, data for this endpoint were not collected. | Posted | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Left Atrial Ejection Fraction (LAEF) at 2-3 Hours Post-dose on Day 8 | Assessment of LAEF was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | Due to early termination of the study, data for this endpoint were not collected. | Posted | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVi) at 2-3 Hours Post-dose on Day 8 | Assessment of LV volume was performed using MRI using LV end systolic volume (LVESV), 2-3 hours after dosing on Day 8 of each treatment period. LVESV was normalized to BSA to provide the indexed counterpart (LVESVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm^3/m^2 | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Right Ventricular End Systolic Volume Index (RVESVi) at 2-3 Hours Post-dose on Day 8 | Assessment of RV volume was performed using MRI using RV end systolic volume (RVESV), 2-3 hours after dosing on Day 8 of each treatment period. RVESV was normalized to BSA to provide the indexed counterpart (RVESVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | cm^3/m^2 | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Pulsatility Index Aorta (PIAo) at 2-3 Hours Post-dose on Day 8 | Assessment of PIAo was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | percent | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| Secondary | Change From Baseline in Pulmonary Artery Pulsatility Index (PAPi) at 2-3 Hours Post-dose on Day 8 | Assessment of PAPi was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period. Baseline was defined as the pre-dose value on Day 1 of treatment period 1. | All randomized subjects. | Posted | Mean | Standard Deviation | percent | Baseline and Day 8 of either treatment period 1 or 2, as applicable. |
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| 0 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | Placebo | Placebo MDI was administered as 2 inhalations BID for 7 days in either treatment period 1 or treatment period 2. | 0 | 4 | 0 | 4 | 1 | 4 |
Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |