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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000716-18 | EudraCT Number |
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Evaluate the superiority of CHF 5993 100/6/12.5 µg Pressurised Metered Dose Inhaler (pMDI) (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate (FF) plus glycopyrronium bromide [GB]) versus CHF 1535 100/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate [FF]), with regard to lung functions parameters and rate of exacerbations as well as safety and health economics outcomes, in adult patients with uncontrolled asthma on medium doses of inhaled corticosteroids in combination with long acting ß2 agonists (LABA).
This study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, and following all other requirements of local laws.
From screening to the end of treatment, vital signs were recorded pre-dose at screening and pre- and postdose at all visits during the treatment period; physical examination was performed at all visits; concomitant medications and adverse events (AEs) were recorded, and asthma exacerbations were assessed at all visits; lung function tests were performed (pre-dose for forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) from screening to end of treatment visits, pre-dose for inspiratory capacity and vital capacity and postdose serial spirometry at all visits during the treatment period).
Patients completed the electronic diary from home twice daily from the time of screening until the end of treatment, to record asthma symptoms, treatment compliance, and use of rescue medication. Patients used the electronic peak flowmeter to record peak expiratory flow twice daily from home from the time of screening until the end of treatment.
Asthma Control Questionnaire© (ACQ)-7 was completed at screening and all visits during the treatment period. The EuroQuality of Life-5-Dimensional-3-Level questionnaire, and health economic and outcome assessments were competed at all visits during the treatment period.
Rescue medication (salbutamol 100 μg per inhalation) was permitted throughout the treatment period when absolutely needed; the maximum allowed dose was 8 inhalations/day (800 μg).
An independent Data Safety Monitoring Board was established to provide impartial safety evaluation and assurance for patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CHF 5993 100/6/12.5 µg | Experimental | CHF 5993 100/6/12.5 CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate GB=Glycopyrronium Bromide |
|
| CHF 1535 100/6 µg | Active Comparator | CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CHF 5993 100/6/12.5 | Drug | BDP=Beclometasone Dipropionate 100µg; FF=Formoterol Fumarate 6µg; GB=Glycopyrronium Bromide 12.5µg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26 | Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment. FEV1=Forced expiratory volume in the first second | Week 0 (pre-treatment, baseline) to Week 26. |
| 2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period | Asthma exacerbation (events): Moderate AND Severe. Severe: asthma worsening requiring initiation of treatment with systemic corticosteroids for at least 3 days (courses of corticosteroids separated by ≥1 week treated as separate severe exacerbations). Moderate: ≥1 of the following criteria fulfilled and leading to a change in treatment (sustained increase of ≥1 puff of short acting beta 2-agonist [SABA] for 2 consecutive days) as shown below:
| Week 0 (pre-treatment, baseline) to Week 52. |
| Measure | Description | Time Frame |
|---|---|---|
| 3_Change From Baseline in Peak(0-3h) FEV1 at Week 26 | Peak FEV1 was analysed within 3 hours post-dose. FEV1=Peak of forced expiratory volume in the first second | Week 0 (pre-treatment, baseline) and Week 26. |
| 4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christian Virchow, MD | Facharzt für Innere Medizin Rostock, Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chiesi Clinical Trial Site 276814 | Rostock | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31582314 | Result | Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S, Zuccaro F, Vele A, Kots M, Georges G, Petruzzelli S, Canonica GW. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019 Nov 9;394(10210):1737-1749. doi: 10.1016/S0140-6736(19)32215-9. Epub 2019 Sep 30. | |
| 36472162 |
| Label | URL |
|---|---|
| Study Record on EU Clinical Trials Register including results. | View source |
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Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol, and the full Clinical Study Report (CSR), providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared patient-level data is anonymized to protect personally identifiable information.
Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.
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Chiesi access criteria and complete process for clinical trial data sharing is available on the Chiesi Group website.
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Overall, 1628 patients were screened according to inclusion and exclusion criteria; of these,1155 patients were randomised. Overall, 5 patients were randomised in error and did not start treatment (N=3 patients in the CHF 5993 pMDI 100/6/12.5 μg group and N=2 patients in the CHF 1535 pMDI 100/6 μg group). The data set Safety population, used for the evaluations represents 1150 patients.
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| ID | Title | Description |
|---|---|---|
| FG000 | CHF 5993 100/6/12.5 µg | CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB |
| FG001 | CHF 1535 100/6 µg | CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | CHF 5993 100/6/12.5 µg | CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB |
| BG001 | CHF 1535 100/6 µg | CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26 | Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment. FEV1=Forced expiratory volume in the first second | Intention to treat (ITT) population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter | Week 0 (pre-treatment, baseline) to Week 26. |
|
Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation.
Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation.
The Safety population was defined as all randomised patients who received at least one dose of 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 | CHF 5993 100/6/12.5 µg | CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood pressure increased | Investigations | MedDRA 18.1 | 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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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 12, 2016 | Feb 12, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 27, 2018 | Feb 12, 2026 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| CHF 1535 100/6 µg | Drug | BDP=Beclometasone Dipropionate 100µg; FF=Formoterol Fumarate 6µg. |
|
Change from baseline in the average morning PEF over the 26-Week treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation. |
| Week 0 (pre-treatment, baseline) to Week 26. |
| 5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis | Severe Asthma Exacerbation Rate over the 52-Week Treatment Period in a pre-specified pooled analysis of 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | The entire treatment period; up to Week 52. |
| 6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits | Change from baseline in peak FEV1 (within 3 h post-dosing) at all clinical visits. Baseline for pre-dose FEV1 was calculated as average of the FEV1 measurements (L) from the visit 2 (V2) Pre45min & V2 Pre15min. If one of the two pre-dose values was missing, the baseline was equal to the available pre-dose value. | Week 0 (pre-treatment, baseline) to Week 52. |
| 7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits | Results show the change from baseline in pre-dose FEV1 at all clinical visits. | Week 0 (pre-treatment, baseline) to Week 52. |
| 8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52 | Results show the percentage of patients classified as FEV1 responders at both Week 26 and Week 52. FEV1 response: Change from baseline in pre-dose morning FEV1 ≥ 100 mL. | Week 0 (pre-treatment, baseline) to Week 26 and Week 52. |
| 9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits | Baseline definition: mean of two pre-dose FEV1 measurements at visit 2 (V2). Results show the change from baseline in FEV1 area under the curve [AUC] (0-3h) at all subsequent visits (i.e. change from baseline of the AUC of the serial post-dose spirometry assessments till 3h post-dose). | Week 0 (pre-treatment, baseline) to Week 52. |
| 10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits | ACQ-7 Questionnaire. Asthma Control Questionnaire-7 (ACQ-7) allows assessment of asthma control in individual patients. The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on lung function (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control (no impairment) and 6 indicating poor control (maximum impairment). The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. Baseline for ACQ-7 was the total score recorded at Visit 2 (Week 0) of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. A negative change from baseline indicates improvement in lung function. | Week 0 (pre-treatment, baseline) to Week 52. |
| 11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52 | Asthma Control Questionnaire (ACQ) and Asthma Control Questionnaire-7 (QAC-7) are defined in the description of Outcome measure 10 above. An ACQ-7 response was defined as change from baseline (Week 0, pre-dose) in ACQ-7 score ≤ -0.5; non-response was defined as change from baseline in ACQ-7 score >-0.5 or missing data. Results represent the responders (i.e. change from baseline in ACQ-7 Score ≤ -0.5) at Week 26 and Week 52. | Week 0 (pre-treatment, baseline) to Week 26 and Week 52 |
| 12a_Change From Baseline in Average Morning PEF (L/Min) Over 52 Weeks of Treatment | Change from baseline in average MORNING PEF (L/min) over 52 weeks of treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation. | Week 0 (pre-treatment, baseline) to Week 52. |
| 12b_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment | Change from baseline in average EVENING PEF (L/min) over 26 and 52 weeks of treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation. | Week 0 (pre-treatment, baseline) to Week 26 and Week 52. |
| 13_Number of Patients at Risk of Moderate or Severe Asthma Exacerbation Over 52 Weeks | Data were analysed for the number of patients at risk of a moderate or severe asthma exacerbation. Results show the number of patients who had moderate or severe asthma exacerbation over the 52 weeks treatment period. | Week 0 (pre-treatment, baseline) to Week 52. |
| 14_Number of Patients at Risk of Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02 | Data were analysed for the number of patients at risk of a severe asthma exacerbation in the pooled analysis of the two pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of patients who had a severe asthma exacerbation over the 52 weeks treatment period. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | Week 0 (Baseline) to 52 weeks for both studies in the pooled analysis. |
| 15_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02. | Moderate asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-055993AB2-02 (TRIGGER). The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | Week 0 (pre-treatment, baseline) to Week 52. |
| 16_Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02 | Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | Week 0 (pre-treatment, baseline) to Week 52. |
| 17_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02 | Moderate and severe asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of participants with moderate and severe asthma exacerbation. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | Week 0 (pre-treatment, baseline) to Week 52. |
| 18_Number of Patients at Risk of Moderate OR Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02 | Time to first moderate or severe asthma exacerbation in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of participants with moderate or severe asthma exacerbation. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | Week 0 (pre-treatment, baseline) to Week 52. |
| 19_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period | Moderate asthma exacerbation rate over the 52-Week treatment period. | Week 0 (pre-treatment, baseline) to Week 52. |
| 20_Number of Patients at Risk of a MODERATE Asthma Exacerbation | Data were analysed for the number of patients at risk of a MODERATE asthma exacerbation. | Week 0 (pre-treatment, baseline) to Week 52. |
| 21a_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods | Change from baseline in the average use of rescue medication over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. | Week 0 (pre-treatment, baseline) to Week 26 and Week 52. |
| 21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period | Results show the change from baseline in the average use (puffs/day) of rescue medication in each inter-visit period. Data was collected through an electronic daily diary from screening to the end of the study. | Week 0 (pre-treatment, baseline) to Week 52. |
| 22a_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods | Change from baseline in the percentage of rescue medication-free days in each inter-visit period over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. | Week 0 (pre-treatment, baseline) to Week 52. |
| 22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment | Results show the change from baseline in the percentage of rescue medication-free days in each inter-visit period over the entire treatment. Data was collected through an electronic daily diary from screening to the end of the study. | Week 0 (pre-treatment, baseline) to Week 52. |
| 23a_Change From Baseline in the Average Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods | Data was collected through an electronic daily diary from screening to the end of the study. Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Weeks of treatment. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered: cough, wheeze, chest tightness, breathlessness.
| Week 0 (pre-treatment, baseline) to Week 52. |
| 23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period | Results show the change from baseline in the average daily asthma symptom scores in each inter-visit period over the entire treatment. Data was collected daily through an electronic diary from screening to the end of the study. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered: cough, wheeze, chest tightness, breathlessness.
| Week 0 (pre-treatment, baseline) to Week 52. |
| 24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods | Change from baseline in the percentage of asthma symptom-free days over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Week treatment periods. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness. An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23. | Week 0 (pre-treatment, baseline) to Week 52. |
| 24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods | Results show the change from baseline in the percentage of asthma symptom-free days in each inter-visit periods over the entire treatment. Data was collected through an electronic daily diary from screening to end of the study. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness. An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23. | Week 0 (pre-treatment, baseline) to Week 52. |
| 25a_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods | Results show the change from baseline in the percentage of asthma control days over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness): Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all). Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity). | Week 0 (pre-treatment, baseline) to Week 52. |
| 25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period | Results show the change from baseline in the percentage of asthma control days in each inter-visit period. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Data was collected through an electronic daily diary from screening to the end of the study Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness): Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all). Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity). | Week 0 (pre-treatment, baseline) to Week 52. |
| Derived |
| Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2. |
| 35872377 | Derived | Orlovic M, Magni T, Lukyanov V, Guerra I, Madoni A. Cost-effectiveness of single-inhaler extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium in patients with uncontrolled asthma in England. Respir Med. 2022 Sep;201:106934. doi: 10.1016/j.rmed.2022.106934. Epub 2022 Jul 19. |
| 35450196 | Derived | Papi A, Singh D, Virchow JC, Canonica GW, Vele A, Georges G. Normalisation of airflow limitation in asthma: Post-hoc analyses of TRIMARAN and TRIGGER. Clin Transl Allergy. 2022 Apr 17;12(4):e12145. doi: 10.1002/clt2.12145. eCollection 2022 Apr. |
| 33121501 | Derived | Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER. Respir Res. 2020 Oct 29;21(1):285. doi: 10.1186/s12931-020-01558-y. |
| 32430414 | Derived | Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Extrafine triple therapy in patients with asthma and persistent airflow limitation. Eur Respir J. 2020 Sep 24;56(3):2000476. doi: 10.1183/13993003.00476-2020. Print 2020 Sep. No abstract available. |
| Time course of exacerbation reduction with extrafine beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) pMDI in adults with moderate to severe asthma: A post-hoc analysis of the TRIMARAN and TRIGGER Studies | View source |
| TRIple in asthMA With uncontRolled pAtient on Medium streNgth of ICS + LABA (TRIMARAN) ClinicalTrials.gov ID NCT02676076 | View source |
| Study Record on EU Clinical Trials Register including results. Study CCD-05993AB2-02; TRIGGER; | View source |
| TRIple in Asthma hiGh strenGth vErsus Ics/ Laba hs and tiotRopium (TRIGGER) | View source |
| Withdrawal by Subject |
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| Protocol Violation |
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| Adverse Event |
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| Lost to Follow-up |
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| Unknown Reason not specified |
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| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Body mass index | Mean | Standard Deviation | kg/m^2 |
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| Body mass index - subgroups | BMI in kg/m^2, is shown in subgroups. | Count of Participants | Participants |
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| Duration of asthma disease | Mean | Standard Deviation | years |
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| Duration of asthma disease by group | Count of Participants | Participants |
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| Number of asthma exacerbations in the previous year | Mean | Standard Deviation | asthma exacerbations |
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| Time since last documented asthma exacerbation | Mean | Standard Deviation | months |
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| Asthma medication at study entry | Count of Participants | Participants |
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| Use of spacer device before study entry | Count of Participants | Participants |
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| Smoking status at screening | Count of Participants | Participants |
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| Smoking duration | Row population differs from the 'Overall' number of subjects because only ex-smokers are considered for the baseline characteristic. | Mean | Standard Deviation | years |
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| Number of pack-years | Mean | Standard Deviation | pack-years |
|
CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF |
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| Primary | 2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period | Asthma exacerbation (events): Moderate AND Severe. Severe: asthma worsening requiring initiation of treatment with systemic corticosteroids for at least 3 days (courses of corticosteroids separated by ≥1 week treated as separate severe exacerbations). Moderate: ≥1 of the following criteria fulfilled and leading to a change in treatment (sustained increase of ≥1 puff of short acting beta 2-agonist [SABA] for 2 consecutive days) as shown below:
| ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | events/year | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 3_Change From Baseline in Peak(0-3h) FEV1 at Week 26 | Peak FEV1 was analysed within 3 hours post-dose. FEV1=Peak of forced expiratory volume in the first second | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter | Week 0 (pre-treatment, baseline) and Week 26. |
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| Secondary | 4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment | Change from baseline in the average morning PEF over the 26-Week treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter/min | Week 0 (pre-treatment, baseline) to Week 26. |
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| Secondary | 5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis | Severe Asthma Exacerbation Rate over the 52-Week Treatment Period in a pre-specified pooled analysis of 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | events/year | The entire treatment period; up to Week 52. |
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| Secondary | 6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits | Change from baseline in peak FEV1 (within 3 h post-dosing) at all clinical visits. Baseline for pre-dose FEV1 was calculated as average of the FEV1 measurements (L) from the visit 2 (V2) Pre45min & V2 Pre15min. If one of the two pre-dose values was missing, the baseline was equal to the available pre-dose value. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits | Results show the change from baseline in pre-dose FEV1 at all clinical visits. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52 | Results show the percentage of patients classified as FEV1 responders at both Week 26 and Week 52. FEV1 response: Change from baseline in pre-dose morning FEV1 ≥ 100 mL. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (pre-treatment, baseline) to Week 26 and Week 52. |
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| Secondary | 9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits | Baseline definition: mean of two pre-dose FEV1 measurements at visit 2 (V2). Results show the change from baseline in FEV1 area under the curve [AUC] (0-3h) at all subsequent visits (i.e. change from baseline of the AUC of the serial post-dose spirometry assessments till 3h post-dose). | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits | ACQ-7 Questionnaire. Asthma Control Questionnaire-7 (ACQ-7) allows assessment of asthma control in individual patients. The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on lung function (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control (no impairment) and 6 indicating poor control (maximum impairment). The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. Baseline for ACQ-7 was the total score recorded at Visit 2 (Week 0) of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. A negative change from baseline indicates improvement in lung function. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52 | Asthma Control Questionnaire (ACQ) and Asthma Control Questionnaire-7 (QAC-7) are defined in the description of Outcome measure 10 above. An ACQ-7 response was defined as change from baseline (Week 0, pre-dose) in ACQ-7 score ≤ -0.5; non-response was defined as change from baseline in ACQ-7 score >-0.5 or missing data. Results represent the responders (i.e. change from baseline in ACQ-7 Score ≤ -0.5) at Week 26 and Week 52. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (pre-treatment, baseline) to Week 26 and Week 52 |
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| Secondary | 12a_Change From Baseline in Average Morning PEF (L/Min) Over 52 Weeks of Treatment | Change from baseline in average MORNING PEF (L/min) over 52 weeks of treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter/min | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 12b_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment | Change from baseline in average EVENING PEF (L/min) over 26 and 52 weeks of treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | Liter/min | Week 0 (pre-treatment, baseline) to Week 26 and Week 52. |
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| Secondary | 13_Number of Patients at Risk of Moderate or Severe Asthma Exacerbation Over 52 Weeks | Data were analysed for the number of patients at risk of a moderate or severe asthma exacerbation. Results show the number of patients who had moderate or severe asthma exacerbation over the 52 weeks treatment period. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 14_Number of Patients at Risk of Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02 | Data were analysed for the number of patients at risk of a severe asthma exacerbation in the pooled analysis of the two pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of patients who had a severe asthma exacerbation over the 52 weeks treatment period. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (Baseline) to 52 weeks for both studies in the pooled analysis. |
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| Secondary | 15_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02. | Moderate asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-055993AB2-02 (TRIGGER). The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | events/year | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 16_Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02 | Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 17_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02 | Moderate and severe asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of participants with moderate and severe asthma exacerbation. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | events/year | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 18_Number of Patients at Risk of Moderate OR Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02 | Time to first moderate or severe asthma exacerbation in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of participants with moderate or severe asthma exacerbation. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 19_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period | Moderate asthma exacerbation rate over the 52-Week treatment period. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | events/year | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 20_Number of Patients at Risk of a MODERATE Asthma Exacerbation | Data were analysed for the number of patients at risk of a MODERATE asthma exacerbation. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Count of Participants | Participants | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 21a_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods | Change from baseline in the average use of rescue medication over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | puffs/day | Week 0 (pre-treatment, baseline) to Week 26 and Week 52. |
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| Secondary | 21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period | Results show the change from baseline in the average use (puffs/day) of rescue medication in each inter-visit period. Data was collected through an electronic daily diary from screening to the end of the study. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Mean | Standard Deviation | puffs/day | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 22a_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods | Change from baseline in the percentage of rescue medication-free days in each inter-visit period over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | percentage of days | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment | Results show the change from baseline in the percentage of rescue medication-free days in each inter-visit period over the entire treatment. Data was collected through an electronic daily diary from screening to the end of the study. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Mean | Standard Deviation | percentage of days | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 23a_Change From Baseline in the Average Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods | Data was collected through an electronic daily diary from screening to the end of the study. Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Weeks of treatment. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered: cough, wheeze, chest tightness, breathlessness.
| ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period | Results show the change from baseline in the average daily asthma symptom scores in each inter-visit period over the entire treatment. Data was collected daily through an electronic diary from screening to the end of the study. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered: cough, wheeze, chest tightness, breathlessness.
| ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Mean | Standard Deviation | score on a scale | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods | Change from baseline in the percentage of asthma symptom-free days over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Week treatment periods. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness. An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | percentage of days | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods | Results show the change from baseline in the percentage of asthma symptom-free days in each inter-visit periods over the entire treatment. Data was collected through an electronic daily diary from screening to end of the study. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness. An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23. | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Mean | Standard Deviation | percentage of days | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 25a_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods | Results show the change from baseline in the percentage of asthma control days over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness): Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all). Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity). | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Least Squares Mean | 95% Confidence Interval | percentage of days | Week 0 (pre-treatment, baseline) to Week 52. |
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| Secondary | 25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period | Results show the change from baseline in the percentage of asthma control days in each inter-visit period. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Data was collected through an electronic daily diary from screening to the end of the study Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness): Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all). Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity). | ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline. | Posted | Mean | Standard Deviation | percentage of days | Week 0 (pre-treatment, baseline) to Week 52. |
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|
|
|
| 3 |
| 576 |
| 28 |
| 576 |
| 429 |
| 576 |
| EG001 | CHF 1535 100/6 µg | CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF | 0 | 574 | 22 | 574 | 451 | 574 |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Systematic Assessment |
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| Mantle cell lymphoma stage IV | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Systematic Assessment |
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| Ovarian cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Systematic Assessment |
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| Squamous cell carcinoma of the cervix | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Systematic Assessment |
|
| Aortic aneurysm rupture | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
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| Hypertensive crisis | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
|
| Subclavian artery stenosis | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
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| Venous thrombosis limb | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Tonsillar inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Limb crushing injury | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
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| Cardiac failure acute | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
|
| Coronary artery disease | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
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| Left ventricular failure | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
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| Myocardial ischaemia | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
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| Stress cardiomyopathy | Cardiac disorders | MedDRA 18.1 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
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| Abdominal hernia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Pancreatitis acute | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Umbilical hernia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Biliary colic | Hepatobiliary disorders | MedDRA 18.1 | Systematic Assessment |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA 18.1 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 18.1 | Systematic Assessment |
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| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Calculus urinary | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
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| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Bursitis infective | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Chronic sinusitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Erysipelas | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Otitis media chronic | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Pulmonary tuberculosis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Respiratory tract infection viral | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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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.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|
| Week 4 |
|
|
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| < 0.001 |
| Adjusted mean difference |
| 0.075 |
| 2-Sided |
| 95 |
| 0.033 |
| 0.116 |
| Superiority |
| Week 12 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.005 | Adjusted mean difference | 0.062 | 2-Sided | 95 | 0.019 | 0.105 | Superiority |
| Week 26 Change from Baseline | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.084 | 2-Sided | 95 | 0.040 | 0.129 | Superiority |
| Week 40 Change from Baseline | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.092 | 2-Sided | 95 | 0.047 | 0.137 | Superiority |
| Week 52 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.006 | Adjusted mean difference | 0.066 | 2-Sided | 95 | 0.019 | 0.112 | Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| 0.163 |
| Adjusted mean difference |
| 0.029 |
| 2-Sided |
| 95 |
| -0.012 |
| 0.070 |
| Superiority |
| Week 26 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.008 | Adjusted mean difference | 0.057 | 2-Sided | 95 | 0.015 | 0.099 | Superiority |
| Week 40 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.010 | Adjusted mean difference | 0.058 | 2-Sided | 95 | 0.014 | 0.101 | Superiority |
| Week 52 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.096 | Adjusted mean difference | 0.038 | 2-Sided | 95 | -0.007 | 0.082 | Superiority |
| 0.104 |
| Odds Ratio (OR) |
| 1.213 |
| 2-Sided |
| 95 |
| 0.961 |
| 1.530 |
| Superiority |
| Week 4 |
|
|
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| < 0.001 |
| Adjusted mean difference |
| 0.076 |
| 2-Sided |
| 95 |
| 0.037 |
| 0.115 |
| Superiority |
| Week 12 Change from baseline | Linear Mixed Model for Repeated Measures | 0.007 | Adjusted mean difference | 0.057 | 2-Sided | 95 | 0.016 | 0.099 | Superiority |
| Week 26 Change from baseline | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.085 | 2-Sided | 95 | 0.041 | 0.129 | Superiority |
| Week 40 Change from baseline | Linear Mixed Model for Repeated Measures | < 0.001 | Adjusted mean difference | 0.086 | 2-Sided | 95 | 0.042 | 0.129 | Superiority |
| Week 52 Change from baseline | Linear Mixed Model for Repeated Measures | 0.009 | Adjusted mean difference | 0.060 | 2-Sided | 95 | 0.015 | 0.106 | Superiority |
| Week 12 |
|
|
| Week 26 |
|
|
| Week 40 |
|
|
| Week 52 |
|
|
| 0.666 |
| Adjusted mean difference |
| -0.017 |
| 2-Sided |
| 95 |
| -0.092 |
| 0.059 |
| Superiority |
| Week 26 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.274 | Adjusted mean difference | -0.043 | 2-Sided | 95 | -0.120 | 0.034 | Superiority |
| Week 40 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.277 | Adjusted mean difference | -0.045 | 2-Sided | 95 | -0.125 | 0.036 | Superiority |
| Week 52 Change from Baseline | Linear Mixed Model for Repeated Measures | 0.575 | Adjusted mean difference | -0.023 | 2-Sided | 95 | -0.103 | 0.057 | Superiority |
| 0.573 |
| Odds Ratio (OR) |
| 1.071 |
| 2-Sided |
| 95 |
| 0.848 |
| 1.362 |
| Superiority |
| Weeks 1-52 |
|
|
| Linear Mixed Model for Repeated Measures |
| <0.001 |
| Adjusted mean difference |
| 12.681 |
| 2-Sided |
| 95 |
| 7.288 |
| 18.073 |
| Superiority |
| Weeks 1-52 |
|
|
| Linear Mixed Model for Repeated Measures |
| 0.932 |
| Adjusted mean difference |
| 0.004 |
| 2-Sided |
| 95 |
| -0.089 |
| 0.097 |
| Superiority |
| Visit 3 - Visit 4 Weeks 5-12 |
|
|
| Visit 4 - Visit 5 Weeks 13-26 |
|
|
| Visit 5 - Visit 6 Weeks 27-40 |
|
|
| Visit 6 - Visit 7 Weeks 41-52 |
|
|
| Weeks 1-52 |
|
|
| Linear Mixed Model for Repeated Measures |
| 0.879 |
| Adjusted mean difference |
| 0.879 |
| 2-Sided |
| 95 |
| -3.178 |
| 2.720 |
| Superiority |
| Visit 3 - Visit 4 Weeks 5-12 |
|
|
| Visit 4 - Visit 5 Weeks 13-26 |
|
|
| Visit 5 - Visit 6 Weeks 27-40 |
|
|
| Visit 6 - Visit 7 Weeks 41-52 |
|
|
| Weeks 1-52 |
|
|
| 0.466 |
| Adjusted mean difference |
| 0.014 |
| 2-Sided |
| 95 |
| -0.024 |
| 0.052 |
| Superiority |
| Visit 3 - Visit 4 Weeks 5-12 |
|
|
| Visit 4 - Visit 5 Weeks 13-26 |
|
|
| Visit 5 - Visit 6 Weeks 27-40 |
|
|
| Visit 6 - Visit 7 Weeks 41-52 |
|
|
| Weeks 1-52 |
|
|
| 0.574 |
| Adjusted mean difference |
| 0.931 |
| 2-Sided |
| 95 |
| -2.320 |
| 4.182 |
| Superiority |
| Visit 3 - Visit 4 Weeks 5-12 |
|
|
| Visit 4 - Visit 5 Weeks 13-26 |
|
|
| Visit 5 - Visit 6 Weeks 27-40 |
|
|
| Visit 6 - Visit 7 Weeks 41-52 |
|
|
| Weeks 1-52 |
|
|
| 0.427 |
| Adjusted mean difference |
| 1.286 |
| 2-Sided |
| 95 |
| -1.887 |
| 4.459 |
| Superiority |
| Visit 3 - Visit 4 Weeks 5-12 |
|
|
| Visit 4 - Visit 5 Weeks 13-26 |
|
|
| Visit 5 - Visit 6 Weeks 27-40 |
|
|
| Visit 6 - Visit 7 Weeks 41-52 |
|
|
| Linear Mixed Model for Repeated Measures |
| 0.136 |
| Adjusted mean difference |
| 2.231 |
| 2-Sided |
| 95 |
| -0.701 |
| 5.162 |
| Superiority |
| Visit 4 - Visit 5 Weeks 13-26 Change From Baseline | Linear Mixed Model for Repeated Measures | 0.332 | Adjusted mean difference | 1.684 | 2-Sided | 95 | -1.723 | 5.092 | Superiority |
| Visit 5 - Visit 6 Weeks 27-40 Change From Baseline | Linear Mixed Model for Repeated Measures | 0.541 | Adjusted mean difference | 1.164 | 2-Sided | 95 | -2.571 | 4.899 | Superiority |
| Visit 6 - Visit 7 Weeks 41-52 Change From Baseline | Linear Mixed Model for Repeated Measures | 0.839 | Adjusted mean difference | 0.407 | 2-Sided | 95 | -3.529 | 4.343 | Superiority |