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Randomized, Phase IIIb, Three-period, Three-treatment, Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects with Moderate to Very Severe COPD after 4 Weeks of Treatment with PT003, Open-Label Spiriva® Respimat® (Tiotropium Bromide) as an Active Control, and Placebo.
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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) |
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| Placebo MDI | Placebo Comparator | Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol |
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| Spiriva® Respimat® (Tiotropium Bromide) | Active Comparator | Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GFF MDI (PT003) | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| FEV1 AUC12-24 | Normalized FEV1 AUC12-24 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29 |
| FEV1 AUC0-12 | Normalized FEV1 AUC0-12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Colin Reisner, MD | Pearl Therapeutics | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28821260 | Derived | Reisner C, Gottschlich G, Fakih F, Koser A, Krainson J, Delacruz L, Arora S, Feldman G, Pudi K, Siddiqui S, Orevillo C, Maes A, St Rose E, Martin U. 24-h bronchodilation and inspiratory capacity improvements with glycopyrrolate/formoterol fumarate via co-suspension delivery technology in COPD. Respir Res. 2017 Aug 18;18(1):157. doi: 10.1186/s12931-017-0636-4. |
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Study to assess the efficacy and safety of GFF MDI 14.4/9.6µg relative to either Placebo MDI or Spiriva Respimat 5µg. Subjects were randomized into 1 of 6 treatment sequences, and all treatment sequences included all 3 treatments. By-treatment sequence tabulations of the data were not pre-specified.
This study was conducted at 10 sites in the US from February 2015 to August 2015. The study was anticipated to run for approximately 9 months but not expected to exceed 12 months.
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| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study | All Subjects Randomized |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo MDI | Drug |
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| Spiriva® Respimat® (Tiotropium Bromide) | Drug | Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva) |
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| Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29 |
| Peak Change From Baseline in FEV1 Evening | Peak Change From Baseline in FEV1 Evening | Baseline and Day 29 |
| Peak Change From Baseline in FEV1 Morning | Peak Change From Baseline in FEV1 Morning | Baseline and Day 29 |
| Morning Pre-Dose Trough FEV1 on Day 29 | Morning Pre-Dose Trough FEV1 on Day 29 | Day 29 |
| Morning Pre-Dose Trough FEV1 on Day 30 | Morning Pre-Dose Trough FEV1 on Day 30 | Day 30 |
| Peak Change From Baseline in IC (Inspiratory Capacity) Evening | Peak Change From Baseline in IC Evening | Baseline and Day 29 |
| Peak Change From Baseline in IC Morning | Peak Change From Baseline in IC Morning | Baseline and Day 29 |
| GFF MDI 14.4/9.6 µg |
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| Placebo MDI |
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| Spiriva Respimat 5 µg |
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| COMPLETED |
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| NOT COMPLETED |
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MITT population was a subset of the ITT Population including subjects who received treatment and had post treatment efficacy data from at least 2 treatment periods and this population is used for baseline characteristics. Participant Flow includes all patients randomized, regardless of treatment received.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects |
| Units | Counts |
|---|---|
| Participants |
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| 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 |
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| 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 | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24 | Subjects in the Modified Intent to Treat (MITT) Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29 |
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| Secondary | FEV1 AUC12-24 | Normalized FEV1 AUC12-24 | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29 |
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| ||||||||||||||||||||||||||||||||
| Secondary | FEV1 AUC0-12 | Normalized FEV1 AUC0-12 | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Peak Change From Baseline in FEV1 Evening | Peak Change From Baseline in FEV1 Evening | MITT Population | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline and Day 29 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Peak Change From Baseline in FEV1 Morning | Peak Change From Baseline in FEV1 Morning | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline and Day 29 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Morning Pre-Dose Trough FEV1 on Day 29 | Morning Pre-Dose Trough FEV1 on Day 29 | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 29 |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Morning Pre-Dose Trough FEV1 on Day 30 | Morning Pre-Dose Trough FEV1 on Day 30 | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Day 30 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Peak Change From Baseline in IC (Inspiratory Capacity) Evening | Peak Change From Baseline in IC Evening | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline and Day 29 |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Peak Change From Baseline in IC Morning | Peak Change From Baseline in IC Morning | Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline and Day 29 |
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Adverse events were collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug.
The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Serious adverse events collected from time of consent up to 14 days after last dose of study drug.
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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 | Glycopyrronium Formoterol GFF Metered Dose Inhaler MDI 14.4/9.6µg | 2 | 75 | 5 | 75 | ||
| EG001 | Spiriva Respimat | Spiriva Respimat 5μg | 2 | 73 | 5 | 73 | ||
| EG002 | Placebo | Placebo MDI | 2 | 72 | 6 | 72 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Myocardial Infarction | Cardiac disorders | MedDRA | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Chest pain | General disorders | MedDRA | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Furuncle | Infections and infestations | MedDRA | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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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. | 650-350-2600 | 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 |
|---|---|
| D006024 | Glycopyrrolate |
| D000069447 | Tiotropium Bromide |
| ID | Term |
|---|---|
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009861 | Onium Compounds |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D000470 | Alkaloids |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
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