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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000644-17 | EudraCT Number |
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This was a randomized, placebo-controlled, double-blind, six-sequence, three-period cross-over study in asthma patients. The study consisted of a 14-day screening period, followed by a 14-day run-in period, and a treatment epoch which consists of three treatment periods, with a minimum duration of 14 days each followed (for the 2 first treatment periods) by a wash-out period. The duration of each treatment period may be extended up to a duration of 18 days if needed for operational reasons. The third treatment period was followed by a Study Completion evaluation at 1-7 days following the last dose. The treatment periods were separated by wash-out periods of 14 to 21 days duration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Patients will receive in a sequential order the following interventional treatments: A,B and C. |
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| Sequence 2 | Experimental | Patients will receive in a sequential order the following interventional treatments: B, A and C. |
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| Sequence 3 | Experimental | Patients will receive in a sequential order the following interventional treatments: C, B and A. |
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| Sequence 4 | Experimental | Patients will receive in a sequential order the following interventional treatments : C, A and B. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) | Drug | Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose) |
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| Measure | Description | Time Frame |
|---|---|---|
| FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period | Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo. | At the end of each treatment period day 14 pre-dose to 24 hours post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Trough FEV1 After 24h | FEV1 at approximately 24 h after the last p.m. or penultimate a.m. dose. Morning and evening trough FEV1 (L) were analyzed by time of day. For morning trough FEV1 (L) assessments this meant that the spirometric assessment was done approximately 24 h after last morning dose and approximately 12 h after last evening dose. | At the end of each treatment period day 14 pre-dose to 24 hours post-dose. |
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Inclusion Criteria:
Patients with a documented physician diagnosis of asthma and who additionally meet the following criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Berlin | 10117 | Germany | |||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | Patients received in a sequential order the following interventional treatments: A,B and C. |
| FG001 | Sequence 2 | Patients received in a sequential order the following interventional treatments: B, A and C. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 27, 2018 | Feb 22, 2019 |
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This study is to assess the bronchodilator effects of QVM149 dosed once daily either in the morning or in the evening for 2 weeks compared to placebo. It will provide evidence of the comparability of lung function effects of QVM149 irrespective of the administration schedule
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This is a double-blind masking.
| Sequence 5 | Experimental | Patients will receive in a sequential order the following interventional treatments: A, C and B. |
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| Sequence 6 | Experimental | Patients will receive in a sequential order the following interventional treatments: B, C and A. |
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| Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) | Drug | QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose) |
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| Treatment C: Placebo (morning dose) and placebo (evening dose) | Drug | Placebo (morning dose) and placebo (evening dose) |
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| Peak Expiratory Flow (PEF) | Peak expiratory flow (PEF) is the maximum flow generated during a forceful exhalation, starting from full lung inflationDaily morning and evening peak expiratory flow rate from Day 2 to Day14 during the three treatment periods. | From treatment period start through study completion (up to 19 weeks). |
| Frankfurt Am Main Hessen |
| 60596 |
| Germany |
| Novartis Investigative Site | Großhansdorf | 22947 | Germany |
| Novartis Investigative Site | Hanover | 30625 | Germany |
| Novartis Investigative Site | Wiesbaden | 65187 | Germany |
| Novartis Investigative Site | Groningen | GZ | 9713 | Netherlands |
| Novartis Investigative Site | Machester | M23 9QZ | United Kingdom |
| FG002 | Sequence 3 | Patients received in a sequential order the following interventional treatments: C, B and A. |
| FG003 | Sequence 4 | Patients received in a sequential order the following interventional treatments : C, A and B. |
| FG004 | Sequence 5 | Patients received in a sequential order the following interventional treatments: A, C and B. |
| FG005 | Sequence 6 | Patients received in a sequential order the following interventional treatments: B, C and A. |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 |
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| Period 3 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants randomized to one of six treatment sequences |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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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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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period | Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo. | The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any dose of study drug and experienced no protocol deviations with relevant impact on PD data. | Posted | Least Squares Mean | Standard Error | Liters | At the end of each treatment period day 14 pre-dose to 24 hours post-dose. |
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| Secondary | Trough FEV1 After 24h | FEV1 at approximately 24 h after the last p.m. or penultimate a.m. dose. Morning and evening trough FEV1 (L) were analyzed by time of day. For morning trough FEV1 (L) assessments this meant that the spirometric assessment was done approximately 24 h after last morning dose and approximately 12 h after last evening dose. | The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any dose of study drug and experienced no protocol deviations with relevant impact on PD data | Posted | Least Squares Mean | Standard Error | Liters | At the end of each treatment period day 14 pre-dose to 24 hours post-dose. |
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| Secondary | Peak Expiratory Flow (PEF) | Peak expiratory flow (PEF) is the maximum flow generated during a forceful exhalation, starting from full lung inflationDaily morning and evening peak expiratory flow rate from Day 2 to Day14 during the three treatment periods. | The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any dose of study drug and experienced no protocol deviations with relevant impact on PD data | Posted | Least Squares Mean | Standard Error | L/min | From treatment period start through study completion (up to 19 weeks). |
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Up to 19 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | QVM149 a.m. | QVM149 150/50/80 μg o.d. (indacaterol acetate 150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the morning (plus matching placebo in the evening) | 0 | 35 | 0 | 35 | 11 | 35 |
| EG001 | QVM149 p.m. | QVM149 150/50/80 μg o.d. (indacaterol acetate150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the evening (plus matching placebo in the morning) | 0 | 35 | 0 | 35 | 13 | 35 |
| EG002 | Placebo | Placebo administered in the morning and in the evening | 0 | 36 | 0 | 36 | 16 | 36 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceutical | 862-778-8300 | novartis.email@novartis.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Mar 8, 2017 | Feb 22, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D004417 | Dyspnea |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D012120 | Respiration Disorders |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| 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 |
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| Mean Difference (Net) |
| 0.6152 |
| 2-Sided |
| 90 |
| 0.5437 |
| 0.6868 |
| Other |
A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.' |
| Mixed Models Analysis | Mean Difference (Net) | -0.0057 | 2-Sided | 90 | -0.0760 | 0.0647 | Other | A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.' |
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| Units | Counts |
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| Participants |
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