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The purpose of this study is to evaluate, after 1 week of dosing, the efficacy and safety of PT003 compared with its individual components (PT001 and PT005), placebo and two active comparators to demonstrate superiority of the combination to its components, and to assess the relative contribution of the components compared with placebo, in patients with moderate to very severe COPD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inhaled PT003 (Dose 1) | Experimental | PT003 MDI Dose 1 |
|
| Inhaled PT003 (Dose 2) | Experimental | PT003 MDI Dose 2 |
|
| Inhaled PT005 (Dose 1) | Experimental | PT005 MDI Dose 1 |
|
| Inhaled PT005 (Dose 2) | Experimental | PT005 MDI Dose 2 |
|
| Inhaled Placebo | Placebo Comparator | Placebo MDI |
|
| Tiotropium bromide 18 μg (Spiriva Handihaler®) | Active Comparator | Tiotropium Bromide inhalation powder |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PT003 MDI | Drug | Inhaled PT003 MDI administered as two puffs BID for 7 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| FEV1 AUC 0-12 on Day 7 | Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration | "Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Peak Change From BL in FEV1 on Day 1 | Peak change from Baseline in FEV1 on Day 1 | Day 1 |
| Peak Change From BL in FEV1 on Day 7 | Peak change from Baseline (BL) in FEV1 on Day 7 |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Colin Reisner, M.D. | Pearl Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research of West Florida, Inc. | Clearwater | Florida | 33765 | United States | ||
| American Health Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28061907 | Derived | Reisner C, Fabbri LM, Kerwin EM, Fogarty C, Spangenthal S, Rabe KF, Ferguson GT, Martinez FJ, Donohue JF, Darken P, St Rose E, Orevillo C, Strom S, Fischer T, Golden M, Dwivedi S. A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. Respir Res. 2017 Jan 6;18(1):8. doi: 10.1186/s12931-016-0491-8. |
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Part A: 4-period, 8-treatment, incomplete block cross-over. Subjects randomized to 1 of 48 sequences, each subject received 4 of 8 possible treatments. Part B: 4-period, 4-treatment, full cross-over. Each subject randomized to 1 of 24 sequences and each sequence was assigned to at least 1 subject.
Conducted at 16 sites in Australia, New Zealand and the US from 24 March 2010 -28 October 2010. The entire study period was a maximum of 20 weeks. Chronic dosing (7 days), 4-period, 8-treatment, incomplete block, cross-over conducted in two parts.
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| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study | Sentinel patients were the first 4 patients enrolled to receive one week of treatment with either GFF MDI 72/9.6mcg, GFF MDI 36/9.6 mcg, GP MDI 36 mcg or FF MDI 9.6 mcg because this was the first time GFF MDI was administered to patients with COPD, the sentinel patients provided additional assurance of safety.9.6 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A |
|
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| Formoterol Fumarate 12 μg (Foradil® Aerolizer®) |
| Active Comparator |
Formoterol fumarate inhalation powder 12 μg |
|
| Inhaled PT001 (Dose 1) | Experimental | PT001 MDI Dose 1 |
|
| PT005 MDI | Drug | Inhaled PT005 MDI administered as two puffs BID for 7 days |
|
| Placebo MDI | Drug | Inhaled placebo administered as two puffs BID for 7 days |
|
| Tiotropium bromide 18 μg (Spiriva Handihaler®) | Drug | Inhaled tiotropium bromide 18 μg (Spiriva Handihaler®) administered QD for 7 days |
|
| Formoterol Fumarate 12 μg (Foradil® Aerolizer®) | Drug | Inhaled formoterol fumarate 12 μg (Foradil® Aerolizer®) administered BID for 7 days |
|
| PT001 MDI | Drug | Inhaled PT001 MDI administered as two puffs BID for 7 days |
|
| Day 7 |
| Peak Change From BL in Inspiratory Capacity on Day 1 | Peak change from Baseline in Inspiratory Capacity (IC) on Day 1 | Day 1 |
| Peak Change From BL IC on Day 7 | Peak Change from Baseline Inspiratory Capacity on following 7-day dose administration | Day 7 |
| Time to Onset of Action >=10% Improvement in FEV1 on Day 1 | Time to Onset of Action where the improvement in FEV1 on Day 1 was >=10% | Day 1 |
| Percentage of Patients Achieving >=12% Improvement in FEV1 on Day 1 | Time to Onset of Action where the improvement in FEV1 on Day 1 was >= 12% | Day 1 |
| Change in Morning Pre-dose FEV1 on Day 7 | Change from Baseline in morning pre-dose FEV1 on Day 7 | Day 7 |
| 12 hr Post-dose Trough FEV1 on Day 7 | 12 hour post-dose trough Forced Expiratory Volume in 1 second on Day 7 | Day 7 |
| Change From BL in Mean Morning Pre-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean morning pre-dose daily peak flow rate on Day 7 | Day 7 |
| Change From BL in Mean Morning Post-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean morning post-dose daily peak flow rate on Day 7 | Day 7 |
| Change From BL in Mean Evening Pre-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean evening pre-dose daily peak flow rate on Day 7 | Day 7 |
| Change From BL in Mean Evening Post-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean evening post-dose daily peak flow rate on Day 7 | Day 7 |
| Charlotte |
| North Carolina |
| 28207 |
| United States |
| Clinical Research Institute of Southern Oregon, PC | Medford | Oregon | 97504 | United States |
| Spartanburg Medical Research | Spartanburg | South Carolina | 29303 | United States |
| Austrials | Caringbah | New South Wales | 2229 | Australia |
| Woolcock | Glebe | New South Wales | 2037 | Australia |
| Austrials | Hornsby | New South Wales | 2077 | Australia |
| Austrials | Auchenflower | Queensland | 4066 | Australia |
| Q-Pharm | Herston | Queensland | 4006 | Australia |
| Respiratory Research Foundation - Burnside War Memorial Hospital | Adelaide | South Australia | Australia |
| Monash Medical Centre | Clayton | Victoria | 3168 | Australia |
| Lung Institute of WA | Nedlands | Western Australia | 6006 | Australia |
| Greenlane Clinical Centre | Epsom | Auckland | 1051 | New Zealand |
| NZ Respiratory & Sleep Institute | Greenlane East | Auckland | 1051 | New Zealand |
| Waikato Hospital | Hamilton | Waikato Region | 3240 | New Zealand |
| P3 Research | Crofton Downs | Wellington Region | 6143 | New Zealand |
| GFF MDI 72/9.6mcg |
|
| GFF MDI 36/9.6 µg (PT003) |
|
| GP MDI 36 µg (PT001) |
|
| Spiriva 18 µg |
|
| FF MDI 9.6 µg (PT005) |
|
| FF MDI 7.2 µg (PT005) |
|
| Placebo MDI |
|
| Foradil 12 µg |
|
| COMPLETED |
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| NOT COMPLETED |
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|
| Part B |
|
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Analysis Population included all randomized participants. 118 plus 4 sentinel patients to make 122.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects | All Baseline Subjects |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | 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 | FEV1 AUC 0-12 on Day 7 | Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration | Modified Intent to Treat (MITT) Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | "Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7 |
|
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| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Peak Change From BL in FEV1 on Day 1 | Peak change from Baseline in FEV1 on Day 1 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 1 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Peak Change From BL in FEV1 on Day 7 | Peak change from Baseline (BL) in FEV1 on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Peak Change From BL in Inspiratory Capacity on Day 1 | Peak change from Baseline in Inspiratory Capacity (IC) on Day 1 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 1 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Peak Change From BL IC on Day 7 | Peak Change from Baseline Inspiratory Capacity on following 7-day dose administration | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Onset of Action >=10% Improvement in FEV1 on Day 1 | Time to Onset of Action where the improvement in FEV1 on Day 1 was >=10% | MITT Population - not including the 4 sentinel patients. | Posted | Number | Participants | Day 1 |
| ||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Patients Achieving >=12% Improvement in FEV1 on Day 1 | Time to Onset of Action where the improvement in FEV1 on Day 1 was >= 12% | MITT Population - not including the 4 sentinel patients. | Posted | Number | Percentage of Participants | Day 1 |
| ||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Morning Pre-dose FEV1 on Day 7 | Change from Baseline in morning pre-dose FEV1 on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 12 hr Post-dose Trough FEV1 on Day 7 | 12 hour post-dose trough Forced Expiratory Volume in 1 second on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From BL in Mean Morning Pre-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean morning pre-dose daily peak flow rate on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters / Minute | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From BL in Mean Morning Post-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean morning post-dose daily peak flow rate on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters / Minute | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From BL in Mean Evening Pre-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean evening pre-dose daily peak flow rate on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters / Minute | Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From BL in Mean Evening Post-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean evening post-dose daily peak flow rate on Day 7 | MITT Population - not including the 4 sentinel patients. | Posted | Least Squares Mean | 95% Confidence Interval | Liters / Minute | Day 7 |
|
Adverse events were collected from the time the subject signed consent through Visit 10/Final Visit (7-14 days post final dose).
Serious Adverse Events (SAE) were captured from the time subjects sign the ICF through the final visit or premature discontinuation visit up to 30 days following the last dose of study drug. Safety population included all participants who were randomized to treatment and received at least one dose of one study treatment.
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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 | GP/FF MDI 72/9.6 μg | GP/FF MDI 72/9.6 μg (PT003) | 0 | 41 | 14 | 41 | ||
| EG001 | GP/FF MDI 36/9.6 μg | GP/FF MDI 36/9.6 μg (PT003) | 1 | 43 | 17 | 43 | ||
| EG002 | GP MDI 36 μg | GP MDI 36 μg (PT001) | 0 | 41 | 10 | 41 | ||
| EG003 | Spiriva | Handihaler 18 μg | 2 | 58 | 9 | 58 | ||
| EG004 | FF MDI 9.6 μg | FF MDI 9.6 μg (PT005) | 1 | 64 | 5 | 64 | ||
| EG005 | FF MDI 7.2 μg | FF MDI 7.2 μg (PT005) | 2 | 64 | 4 | 64 | ||
| EG006 | Placebo | Placebo MDI | 0 | 52 | 4 | 52 | ||
| EG007 | Foradil Aerolizer | Foradil Aerolizer 12 μg | 0 | 55 | 7 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis perforated | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Aortic aneurysm | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA | Systematic Assessment |
| |
| Foreign Body Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry Mouth | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
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 its opinions, or the opinions of the publication committee, if these differ with the proposed publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Colin Reisner, MD, FCCP, FAAAAI | Pearl Therapeutics, Inc | 650-305-2600 | creisner@pearltherapeutics.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| D000068759 | Formoterol Fumarate |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D000588 | Amines |
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| Adverse Event |
|
FF MDI 7.2 μg (PT005)
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
| FF MDI 7.2 μg |
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
| FF MDI 7.2 μg |
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|
| Foradil 12 μg |
Foradil 12 μg |
|
|
| FF MDI 7.2 μg |
FF MDI 7.2 μg (PT005) |
| OG006 | Foradil 12 μg | Foradil 12 μg |
|
|