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Randomized,double-blind,multicenter,multinational,parallel-group,Phase III study to demonstrate the superiority of the triple fixed combination of beclometasone + formoterol + glycopyrrolate (BDP/FF/GB) administered via pressurised metered dose inhaler (pMDI) over the equivalent dose of Foster® (beclometasone dipropionate (BDP) / formoterol fumarate (FF), in patients diagnosed with chronic obstructive pulmonary disease (COPD) after 52 weeks of treatment.
This 52-week randomised 2 parallel groups study evaluated the superiority of fixed triple therapy with Inhaled Corticosteroid (ICS) / Long-Acting β2-Agonist (LABA) / Long-Acting Muscarinic Antagonist (LAMA) compared with ICS/LABA in patients with severe to very severe diagnosed of COPD.
Patients' eligibility was checked during the screening visit including the review of medical history, spirometry assessments, routine labs, physical examination, 12-lead electrocardiogram (ECG), vital signs measurement, prior to entering a 2-week open-label run-in period with BDP/FF to establish a baseline.
After the run-in period, eligible patients were randomised, to either fixed triple therapy BDP/FF/GB or BDP/FF treatment group. During the 52-week treatment period, patients who completed the study did have 5 subsequent visits post randomisation scheduled respectively after 4, 12, 26, 40, and 52 weeks of treatment. During these visits, pre-dose and post-dose spirometry, 12-lead ECG, vital signs, and dyspnoea assessments were performed. Rescue medication use, compliance with the treatment, and EXACT-PRO questionnaire [EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO)] were recorded daily (via an electronic diary) during the run-in and randomised treatment periods.
For pharmacovigilance purposes, adverse events (AE) were recorded from the time of patient informed consent signature until subject's study participation ended (Week 52 or early discontinuation).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Beclometasone/Formoterol/Glycopyrrolate | Experimental | CHF 5993 pMDI 100/6/12.5 µg 2 inhalations bid |
|
| Beclometasone/Formoterol | Active Comparator | Foster® 100/6 µg 2 inhalations bid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Beclometasone/Formoterol/Glycopyrrolate | Drug | Active drug tested |
|
| Measure | Description | Time Frame |
|---|---|---|
| 1_Change From Baseline in Pre-dose Morning Forced Expiratory Volume in the 1st Second (FEV1) -- at Week 26 | Changes from baseline in pre-dose morning FEV1 to visit at Week 26. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Baseline (Week 0), Week 26. |
| 2_Change From Baseline in 2-hour Post-dose FEV1 -- at Week 26 | Change from baseline in 2-hour post-dose FEV1, at Week 26. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Baseline (Week 0) to 2-hour post-dose at Week 26. |
| 3_Transition Dyspnoea Index (TDI) Focal Score -- at Week 26 | Transition Dyspnoea Index (TDI) focal score is a symptom-based variable tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea based on 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI focal score is the baseline value from which TDI focal score is assessed. BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (i.e. from 0 to 12). Change from baseline in dyspnoea severity was measured using the TDI. TDI score ranges from -3 (major deterioration) to +3 (major improvement) for each domain, with the TDI focal score consisting of the sum of each domain (i.e. from -9 to +9). A higher total score indicates improvement, while a lower or negative score indicates worsening symptoms. BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index | Baseline (Week 0), Week 26. |
| Measure | Description | Time Frame |
|---|---|---|
| 4_Change From Baseline in Pre-dose Morning FEV1 -- at All the Other Clinic Visits | Change from baseline in pre-dose morning FEV1, at all the other clinic visits. Please note: results at visit Week 26, are presented as the primary outcome measure #1 for this study. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dave SINGH, MD | University Hospital of South Manchester, MANCHESTER M23 9 QZ, UK | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dr Beatrix BALINT | Szeged | 6722 | Hungary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30587953 | Background | Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018 Dec 12;13:3971-3981. doi: 10.2147/COPD.S185975. eCollection 2018. | |
| 30880943 | Background | Singh D, Fabbri LM, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019. |
| Label | URL |
|---|---|
| EU Clinical Trial Register - Study Record including results | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | CHF 5993 pMDI -- Beclometasone/Formoterol/Glycopyrrolate | CHF 5993 pMDI 100/6/12.5 µg 2 inhalations bid Beclometasone/Formoterol/Glycopyrrolate: Active drug tested pMDI= Pressurised Metered Dose Inhaler |
| FG001 | Foster® pMDI -- Beclometasone/Formoterol | Foster® pMDI 100/6 µg 2 inhalations bid Beclometasone/Formoterol: Active comparator |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety population: all randomised patients who received at least one dose of the study treatment.
One patient in the CHF 1535 pMDI group did not use the study medication kit provided at V2 and withdrew consent a few days after the visit.
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| ID | Title | Description |
|---|---|---|
| BG000 | CHF 5993 pMDI Beclometasone/Formoterol/Glycopyrrolate | Active drug CHF 5993 pMDI (Beclometasone/Formoterol/Glycopyrrolate 100/6/12.5 µg) 2 inhalations bid |
| BG001 | CHF 1535 pMDI Foster® Beclometasone/Formoterol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 1_Change From Baseline in Pre-dose Morning Forced Expiratory Volume in the 1st Second (FEV1) -- at Week 26 | Changes from baseline in pre-dose morning FEV1 to visit at Week 26. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | litre | Baseline (Week 0), Week 26. |
|
Adverse events (AE) were reported from the time of patient informed consent signature until subject's study participation ended (Week 52 or early withdrawal).
Analyses of safety parameters were based on the safety set, defined as all randomised patients who received at least one dose of the study treatment.
Analysis of AEs was performed on Treatment-Emergent Adverse Event (TEAE) principle, defined as AEs with a date of first randomised study medication intake. Therefore, AEs were not analysed for the run-in period.
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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 | Beclometasone/Formoterol/Glycopyrrolate | Active drug CHF 5993 pMDI (Beclometasone/Formoterol/Glycopyrrolate 100/6/12.5 µg) 2 inhalations bid |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adenocarcinoma gastric | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Transparency | Chiesi Farmaceutici S.p.A. | + 39 0521 2791 | clinicaltrials_info@chiesi.com |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D008171 | Lung Diseases |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
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| ID | Term |
|---|---|
| D001507 | Beclomethasone |
| D000068759 | Formoterol Fumarate |
| D005581 | Foster Home Care |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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| Beclometasone/Formoterol | Drug | Active comparator |
|
|
| Baseline (Week 0), Week 4. 12, 40, 52. |
| 5_Change From Baseline to the Average in Pre-dose Morning FEV1 -- Over the Treatment Period | Changes from baseline for the average in pre-dose morning FEV1 over the treatment period. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
| 6_Number of Participants Defined as Responders Wrt. to FEV1 -- Change From Baseline in Pre-dose Morning FEV1 ≥100 mL -- at Week 26 and Week 52 | Number of participants defined as responders wrt. to FEV1 -- at Week 26 and Week 52. FEV1 response was defined as a change from baseline in pre-dose morning FEV1 of ≥100 mL. If the change from baseline was <100 mL, the patient was classified as a non-responder in terms of FEV1. Subjects with missing pre-dose morning FEV1 value at the pre-specified tested time points were also classified as non-responders. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Baseline (Week 0), Week 26, Week 52. |
| 7_Change From Baseline in 2-hour Post-dose of FEV1 -- at All the Other Clinic Visits | Change from baseline in 2-hour post-dose of FEV1, at all the other clinic visits. Please note: a) results at visit Week 26, are presented as the primary outcome measure #2 for this study; b) for Week 0, the measurement shown in the results table below was made 2 h after the baseline measurement i.e. pre-treatment at study baseline. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Baseline (Week 0), Week 4, 12, 40, 52. |
| 8_Change From Pre-dose to 2-hour Post-dose FEV1 -- at All Study Visits | Change from pre-dose to 2-hour post-dose value of FEV1, at study visits on Week 4, 12, 26, 40, and 52. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Week 4, 12, 26, 40, 52. |
| 9_Transition Dyspnoea Index (TDI) Focal Score -- at All Study Visits | TDI focal score is a symptom-based tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea on 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry. Please note: Results at Week 26, are presented as the primary outcome measure #3 for this PRS study entry. BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index | Baseline (Week 0), Week 4, 12, 40, 52. |
| 10_Number of Participants With Transition Dyspnoea Index (TDI) Response (Focal Score ≥1) -- at Week 26 and Week 52 | Number of participants with transition dyspnoea index (TDI) response (focal score ≥1) -- at Week 26 and Week 52. TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry. TDI response was defined as a TDI focal score of ≥1. If the TDI focal score was <1, the patient was classified as a non-responder in terms of TDI. Patients with missing TDI focal score at the pre-specified tested time points were also classified as non-responders. | Week 26, Week 52. |
| 11a_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Total Score | Change from baseline in Saint George's respiratory questionnaire (SGRQ) Total score. SGRQ is a 76-item questionnaire developed to measure health in chronic airflow limitation. SGRQ consists of scores from three component that are used to calculate the total score: Symptoms, Activity, and Impacts on daily life. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, and Week 4, 12, 26, 40, 52). The Total score range is from 0 to 100 (0=Best, 100=Worst); lower scores correspond to better health. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
| 11b_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Symptoms Score | Change from baseline in Saint George's respiratory questionnaire (SGRQ) -- Symptoms Score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Symptoms. The Symptoms score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
| 11c_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Impacts Score | Saint George's respiratory questionnaire (SGRQ) -- Impacts Score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Impacts. The Impact score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
| 11d_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Activity Score | Saint George's respiratory questionnaire (SGRQ) -- Activity score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Activity. The Activity score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
| 12_Number of Participants With Saint George's Respiratory Questionnaire (SGRQ) Response (Change From Baseline in Total Score ≤-4) -- at Week 26 and Week 52 | Number of participants with Saint George's Respiratory Questionnaire (SGRQ) response, defined as a change from baseline in SGRQ total score ≤ -4, at Week 26 and Week 52. If the change from baseline was > -4, the patient was assessed as a non-responder in terms of SGRQ. Patients with missing change from baseline at the pre-specified tested time points were also classified as non-responders. Results shown represent the number of responder participants in terms of SGRQ, for the comparison of CHF 5993 pMDI versus CHF 1535 pMDI. | Baseline (Week 0), Week 26, Week 52. |
| 13a_Change From Baseline for Percentage of Days Without Intake of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment) | Days WITHOUT intake of rescue medication. Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the percentage of days without intake of rescue medication. | Baseline (Week 0) to Week 4, 12, 26, 40, 52. |
| 13b_Change From Baseline for the Average Use of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment) | Average use of rescue medication, over the entire treatment period (52 Weeks of treatment). Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the average use of rescue medication (number of puffs/day). | Baseline (Week 0) to Week 4, 12, 26, 40, 52. |
| 14_Rate of Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Rate -- Over Entire Treatment Period (52 Weeks of Treatment) | Rate of moderate AND severe COPD exacerbations over the entire treatment period of treatment (52 weeks). COPD=Chronic obstructive pulmonary disease | Baseline (Week 0) to Week 52 (entire treatment period). |
| 15_First Occurrence of All Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | First occurrence of at least 1 moderate OR severe COPD exacerbation. First occurrence was analysed by Cox regression as time to first exacerbation and reported as hazard ratio. COPD=Chronic obstructive pulmonary disease | Baseline (Week 0), Week 52. |
| 30792343 | Background | Singh D, Fabbri LM, Corradi M, Georges G, Guasconi A, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation. Eur Respir J. 2019 May 18;53(5):1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May. |
| 27598678 | Result | Singh D, Papi A, Corradi M, Pavlisova I, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016 Sep 3;388(10048):963-73. doi: 10.1016/S0140-6736(16)31354-X. Epub 2016 Sep 1. |
| Adverse Event |
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| Lost to Follow-up |
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| Lack of Efficacy |
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| Protocol Violation |
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| Physician Decision |
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| Moved to another state; could not attend study visits. |
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Active comparator CHF 1535 pMDI Foster® (Beclometasone/Formoterol 100/6 µg ) 2 inhalations bid
| BG002 | Total | Total of all reporting groups |
| years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Patient disposition by country is shown as 'randomised patients', per country and per treatment group. | Number | participants |
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| Time since first COPD diagnosis (years | Mean | Standard Deviation | years |
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| Main COPD phenotype | Phenotype reported as based on Principal Investigator's clinical judgment. | Count of Participants | Participants |
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| Number of COPD exacerbations in the previous year | Count of Participants | Participants |
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| Time since last documented COPD exacerbation | Mean | Full Range | months |
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| COPD medication at study entry | Count of Participants | Participants |
|
| Spacer device use before study entry | Count of Participants | Participants |
|
| Spacer Device use during study | Count of Participants | Participants |
|
| CHF 1535 pMDI Foster® |
Active comparator CHF 1535 pMDI Foster® (Beclometasone/Formoterol 100/6 µg ) 2 inhalations bid |
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| Primary | 2_Change From Baseline in 2-hour Post-dose FEV1 -- at Week 26 | Change from baseline in 2-hour post-dose FEV1, at Week 26. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | litre | Baseline (Week 0) to 2-hour post-dose at Week 26. |
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| Primary | 3_Transition Dyspnoea Index (TDI) Focal Score -- at Week 26 | Transition Dyspnoea Index (TDI) focal score is a symptom-based variable tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea based on 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI focal score is the baseline value from which TDI focal score is assessed. BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (i.e. from 0 to 12). Change from baseline in dyspnoea severity was measured using the TDI. TDI score ranges from -3 (major deterioration) to +3 (major improvement) for each domain, with the TDI focal score consisting of the sum of each domain (i.e. from -9 to +9). A higher total score indicates improvement, while a lower or negative score indicates worsening symptoms. BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline (Week 0), Week 26. |
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| Secondary | 4_Change From Baseline in Pre-dose Morning FEV1 -- at All the Other Clinic Visits | Change from baseline in pre-dose morning FEV1, at all the other clinic visits. Please note: results at visit Week 26, are presented as the primary outcome measure #1 for this study. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | litre | Baseline (Week 0), Week 4. 12, 40, 52. |
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| Secondary | 5_Change From Baseline to the Average in Pre-dose Morning FEV1 -- Over the Treatment Period | Changes from baseline for the average in pre-dose morning FEV1 over the treatment period. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | litre | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
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| Secondary | 6_Number of Participants Defined as Responders Wrt. to FEV1 -- Change From Baseline in Pre-dose Morning FEV1 ≥100 mL -- at Week 26 and Week 52 | Number of participants defined as responders wrt. to FEV1 -- at Week 26 and Week 52. FEV1 response was defined as a change from baseline in pre-dose morning FEV1 of ≥100 mL. If the change from baseline was <100 mL, the patient was classified as a non-responder in terms of FEV1. Subjects with missing pre-dose morning FEV1 value at the pre-specified tested time points were also classified as non-responders. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Count of Participants | Participants | Baseline (Week 0), Week 26, Week 52. |
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| Secondary | 7_Change From Baseline in 2-hour Post-dose of FEV1 -- at All the Other Clinic Visits | Change from baseline in 2-hour post-dose of FEV1, at all the other clinic visits. Please note: a) results at visit Week 26, are presented as the primary outcome measure #2 for this study; b) for Week 0, the measurement shown in the results table below was made 2 h after the baseline measurement i.e. pre-treatment at study baseline. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | litre | Baseline (Week 0), Week 4, 12, 40, 52. |
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| Secondary | 8_Change From Pre-dose to 2-hour Post-dose FEV1 -- at All Study Visits | Change from pre-dose to 2-hour post-dose value of FEV1, at study visits on Week 4, 12, 26, 40, and 52. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. Change from pre-dose to 2h post-dose FEV1 was analysed using a separate model for each week. | Posted | Least Squares Mean | 95% Confidence Interval | liter | Week 4, 12, 26, 40, 52. |
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| Secondary | 9_Transition Dyspnoea Index (TDI) Focal Score -- at All Study Visits | TDI focal score is a symptom-based tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea on 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry. Please note: Results at Week 26, are presented as the primary outcome measure #3 for this PRS study entry. BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline (Week 0), Week 4, 12, 40, 52. |
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| Secondary | 10_Number of Participants With Transition Dyspnoea Index (TDI) Response (Focal Score ≥1) -- at Week 26 and Week 52 | Number of participants with transition dyspnoea index (TDI) response (focal score ≥1) -- at Week 26 and Week 52. TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry. TDI response was defined as a TDI focal score of ≥1. If the TDI focal score was <1, the patient was classified as a non-responder in terms of TDI. Patients with missing TDI focal score at the pre-specified tested time points were also classified as non-responders. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Count of Participants | Participants | Week 26, Week 52. |
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|
| Secondary | 11a_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Total Score | Change from baseline in Saint George's respiratory questionnaire (SGRQ) Total score. SGRQ is a 76-item questionnaire developed to measure health in chronic airflow limitation. SGRQ consists of scores from three component that are used to calculate the total score: Symptoms, Activity, and Impacts on daily life. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, and Week 4, 12, 26, 40, 52). The Total score range is from 0 to 100 (0=Best, 100=Worst); lower scores correspond to better health. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
|
|
|
|
| Secondary | 11b_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Symptoms Score | Change from baseline in Saint George's respiratory questionnaire (SGRQ) -- Symptoms Score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Symptoms. The Symptoms score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
|
|
|
|
| Secondary | 11c_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Impacts Score | Saint George's respiratory questionnaire (SGRQ) -- Impacts Score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Impacts. The Impact score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
|
|
|
|
| Secondary | 11d_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Activity Score | Saint George's respiratory questionnaire (SGRQ) -- Activity score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Activity. The Activity score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline (Week 0), Week 4, 12, 26, 40, 52. |
|
|
|
|
| Secondary | 12_Number of Participants With Saint George's Respiratory Questionnaire (SGRQ) Response (Change From Baseline in Total Score ≤-4) -- at Week 26 and Week 52 | Number of participants with Saint George's Respiratory Questionnaire (SGRQ) response, defined as a change from baseline in SGRQ total score ≤ -4, at Week 26 and Week 52. If the change from baseline was > -4, the patient was assessed as a non-responder in terms of SGRQ. Patients with missing change from baseline at the pre-specified tested time points were also classified as non-responders. Results shown represent the number of responder participants in terms of SGRQ, for the comparison of CHF 5993 pMDI versus CHF 1535 pMDI. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Count of Participants | Participants | Baseline (Week 0), Week 26, Week 52. |
|
|
|
|
| Secondary | 13a_Change From Baseline for Percentage of Days Without Intake of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment) | Days WITHOUT intake of rescue medication. Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the percentage of days without intake of rescue medication. | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | percentage of days | Baseline (Week 0) to Week 4, 12, 26, 40, 52. |
|
|
|
|
| Secondary | 13b_Change From Baseline for the Average Use of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment) | Average use of rescue medication, over the entire treatment period (52 Weeks of treatment). Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the average use of rescue medication (number of puffs/day). | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | puffs/day | Baseline (Week 0) to Week 4, 12, 26, 40, 52. |
|
|
|
|
| Secondary | 14_Rate of Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Rate -- Over Entire Treatment Period (52 Weeks of Treatment) | Rate of moderate AND severe COPD exacerbations over the entire treatment period of treatment (52 weeks). COPD=Chronic obstructive pulmonary disease | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Least Squares Mean | 95% Confidence Interval | events per patient per year | Baseline (Week 0) to Week 52 (entire treatment period). |
|
|
|
|
| Secondary | 15_First Occurrence of All Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | First occurrence of at least 1 moderate OR severe COPD exacerbation. First occurrence was analysed by Cox regression as time to first exacerbation and reported as hazard ratio. COPD=Chronic obstructive pulmonary disease | Intention-to-Treat (ITT) population: defined as all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after baseline. | Posted | Number | number of first occurrences | Baseline (Week 0), Week 52. |
|
|
|
|
| 15 |
| 687 |
| 106 |
| 687 |
| 181 |
| 687 |
| EG001 | Beclometasone/Formoterol | Active comparator CHF 1535 pMDI Foster® (Beclometasone/Formoterol 100/6 µg ) 2 inhalations bid | 16 | 680 | 123 | 680 | 203 | 680 |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Gastrointestinal tract adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Laryngeal cancer stage III | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Lung neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Malignant neoplasm of conjunctiva | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Metastatic gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Pancreatic carcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Prostate cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Squamous cell carcinoma of lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Aortic thrombosis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Femoral artery aneurysm | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Leriche syndrome | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Peripheral ischaemia | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Shock | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Death | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Device malfunction | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Prostatitis | Reproductive system and breast disorders | MedDRA (16.0) | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Lung cyst | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vocal cord leukoplakia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Alcohol abuse | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Multiple fractures | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Multiple injuries | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Pneumothorax traumatic | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Poisoning | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Post procedural fistula | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Post procedural haematoma | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Hydrocele | Congenital, familial and genetic disorders | MedDRA (16.0) | Systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Angina unstable | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arteriosclerosis coronary artery | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cardiac failure acute | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cardiac failure chronic | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cardiopulmonary failure | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cor pulmonale | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Coronary artery stenosis | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Myocardial ischaemia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Sick sinus syndrome | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Supraventricular tachyarrhythmia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ventricular fibrillation | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Carotid artery stenosis | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cerebrovascular disorder | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vertebrobasilar insufficiency | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Haemorrhagic disorder | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Idiopathic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Deafness neurosensory | Ear and labyrinth disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Gastric ulcer perforation | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Haemorrhagic erosive gastritis | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hernial eventration | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Umbilical hernia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Biliary colic | Hepatobiliary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal abscess | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Hepatitis C | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Peripheral artery stenosis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
Results of this study may be published or presented at scientific meetings. If a publication is presented by the Investigator, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor to Chiesi before submission.
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013258 | Steroids, Chlorinated |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D005791 | Patient Care |
| D013812 | Therapeutics |
| D003153 | Community Health Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| Week 12 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| < 0.001 |
| Adjusted mean difference |
| 0.068 |
| 2-Sided |
| 95 |
| 0.042 |
| 0.094 |
| Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.077 | 2-Sided | 95 | 0.046 | 0.108 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.063 | 2-Sided | 95 | 0.032 | 0.094 | Superiority |
| < 0.001 |
| Odds Ratio (OR) |
| 2.061 |
| 2-Sided |
| 95 |
| 1.621 |
| 2.620 |
| Superiority |
| Week 4 |
|
|
| Week 12 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| < 0.001 |
| Adjusted mean difference |
| 0.116 |
| 2-Sided |
| 95 |
| 0.090 |
| 0.141 |
| Superiority |
| Week 12; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.116 | 2-Sided | 95 | 0.087 | 0.144 | Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.102 | 2-Sided | 95 | 0.070 | 0.135 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.103 | 2-Sided | 95 | 0.069 | 0.137 | Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| ANCOVA |
| < 0.001 |
| Adjusted mean difference |
| 0.045 |
| 2-Sided |
| 95 |
| 0.029 |
| 0.062 |
| Superiority |
| Week 26; Adjusted mean difference btw treat groups. | ANCOVA | < 0.001 | Adjusted mean difference | 0.031 | 2-Sided | 95 | 0.015 | 0.047 | Superiority |
| Week 40; Adjusted mean difference btw treat groups. | ANCOVA | = 0.013 | Adjusted mean difference | 0.022 | 2-Sided | 95 | 0.005 | 0.039 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | ANCOVA | < 0.001 | Adjusted mean difference | 0.034 | 2-Sided | 95 | 0.016 | 0.052 | Superiority |
| Week 12 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| = 0.007 |
| Adjusted mean difference |
| 0.38 |
| 2-Sided |
| 95 |
| 0.11 |
| 0.66 |
| Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.343 | Adjusted mean difference | 0.15 | 2-Sided | 95 | -0.16 | 0.45 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.186 | Adjusted mean difference | 0.21 | 2-Sided | 95 | -0.10 | 0.53 | Superiority |
| = 0.430 |
| Odds Ratio (OR) |
| 1.093 |
| 2-Sided |
| 95 |
| 0.877 |
| 1.362 |
| Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| = 0.002 |
| Adjusted mean difference |
| -2.04 |
| 2-Sided |
| 95 |
| -3.30 |
| -0.78 |
| Superiority |
| Week 26; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.051 | Adjusted mean difference | -1.33 | 2-Sided | 95 | -2.66 | 0.01 | Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.057 | Adjusted mean difference | -1.40 | 2-Sided | 95 | -2.85 | 0.04 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.029 | Adjusted mean difference | -1.69 | 2-Sided | 95 | -3.20 | -0.17 | Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| = 0.54 |
| Adjusted mean difference |
| -0.53 |
| 2-Sided |
| 95 |
| -2.24 |
| 1.17 |
| Superiority |
| Week 26; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.077 | Adjusted mean difference | -1.63 | 2-Sided | 95 | -3.44 | 0.17 | Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.224 | Adjusted mean difference | -1.23 | 2-Sided | 95 | -3.21 | 0.75 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.364 | Adjusted mean difference | -0.96 | 2-Sided | 95 | -3.03 | 1.11 | Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| = 0.01 |
| Adjusted mean difference |
| -1.93 |
| 2-Sided |
| 95 |
| -3.4 |
| -0.46 |
| Superiority |
| Week 26; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.079 | Adjusted mean difference | -1.39 | 2-Sided | 95 | -2.93 | 0.16 | Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.054 | Adjusted mean difference | -1.58 | 2-Sided | 95 | -3.19 | 0.03 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.015 | Adjusted mean difference | -2.09 | 2-Sided | 95 | -3.76 | -0.41 | Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| Linear Mixed Model for Repeated Measures |
| = 0.001 |
| Adjusted mean difference |
| -2.57 |
| 2-Sided |
| 95 |
| -4.14 |
| -1.01 |
| Superiority |
| Week 26; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.039 | Adjusted mean difference | -1.71 | 2-Sided | 95 | -3.33 | -0.09 | Superiority |
| Week 40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.065 | Adjusted mean difference | -1.61 | 2-Sided | 95 | -3.32 | -0.10 | Superiority |
| Week 52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.145 | Adjusted mean difference | -1.31 | 2-Sided | 95 | -3.08 | 0.45 | Superiority |
| = 0.014 |
| Odds Ratio (OR) |
| 1.327 |
| 2-Sided |
| 95 |
| 1.06 |
| 1.661 |
| Superiority |
| Week 5-12 |
|
|
| Week 13-26 |
|
|
| Week 27-40 |
|
|
| Week 41-52 |
|
|
| Week 1-52 |
|
|
| Linear Mixed Model for Repeated Measures |
Week 5-12; Adjusted mean difference btw treat groups. |
| = 0.039 |
| Adjusted mean difference |
| 3.05 |
| 2-Sided |
| 95 |
| 0.15 |
| 5.95 |
| Superiority |
| Week 13-26; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.051 | Adjusted mean difference | 3.09 | 2-Sided | 95 | -0.02 | 6.20 | Superiority |
| Week 27-40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.342 | Adjusted mean difference | 1.60 | 2-Sided | 95 | -1.71 | 4.91 | Superiority |
| Week 41-52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.134 | Adjusted mean difference | 2.59 | 2-Sided | 95 | -0.80 | 5.97 | Superiority |
| Week 1-52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.063 | Adjusted mean difference | 2.65 | 2-Sided | 95 | -0.14 | 5.45 | Superiority |
| Week 5-12 |
|
|
| Week 13-26 |
|
|
| Week 27-40 |
|
|
| Week 41-52 |
|
|
| Week 1-52 |
|
|
| Linear Mixed Model for Repeated Measures |
| = 0.016 |
| Adjusted mean difference |
| -0.19 |
| 2-Sided |
| 95 |
| -0.35 |
| -0.04 |
| Superiority |
| Week 13-26; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.029 | Adjusted mean difference | -0.19 | 2-Sided | 95 | -0.35 | -0.02 | Superiority |
| Week 27-40; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.225 | Adjusted mean difference | -0.11 | 2-Sided | 95 | -0.29 | 0.07 | Superiority |
| Week 41-52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.262 | Adjusted mean difference | -0.11 | 2-Sided | 95 | -0.30 | 0.08 | Superiority |
| Week 1-52; Adjusted mean difference btw treat groups. | Linear Mixed Model for Repeated Measures | = 0.062 | Adjusted mean difference | -0.15 | 2-Sided | 95 | -0.31 | 0.01 | Superiority |