Asthma
Conditions
Keywords
QVM149, Asthma, Japanese, Allergic asthma, Allergy triggered asthma, Reactive asthma, Asthma attack, Difficulty breathing
Brief summary
The purpose of this study is to provide long term safety data of QVM149 in Japanese patients with asthma for the registration of QVM149 in Japan.
Interventions
DRUGQVM149
QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed. * Male and female adult patient ≥ 18 years old. * Patients with a diagnosis of persistent asthma (GINA 2016) for a period of at least 1 year prior to Visit 1. * Patients who have used medium or high dose of ICS/LABA combinations for asthma for at least 3 months and at stable dose and regimen for at least 4 weeks prior to Visit 1. * An ACQ-7 score ≥ 1.5 at Visits 2. * Pre-bronchodilator FEV1 of ≥ 40% and ≤ 85% of the predicted normal value for the patient after withholding bronchodilators at Visit 2. o Repeating is allowed once only. Repeating of percentage predicted FEV1 should be done in an ad-hoc visit to be scheduled on a date that would provide sufficient time to receive confirmation from the spirometry data central reviewer of the validity of the assessment before Visit 99. * Patients must demonstrate reversibility defined as an increase in FEV1 of ≥ 12% and 200 mL within 15 to 30 minutes after administration of 400 µg of salbutamol at Visit 2. Spacer devices are permitted during reversibility testing only. The Investigator or delegate may decide whether or not to use a spacer for the reversibility testing. * If reversibility is not proven at Visit 2, patients may be permitted to enter the study with historical evidence of reversibility that was performed within 5 years prior to Visit 1. * Alternatively, patients may be permitted to enter the study with a historical positive bronchoprovocation test (defined as a provoked fall in FEV1 of 20% by bronchoconstriction agent e.g., methacholine, histamine) or equivalent test (e.g., astography) that was performed within 5 years prior to Visit 1. * If reversibility is not proven at Visit 2 and historical data is not available, reversibility should be repeated once in an ad-hoc visit scheduled as close as possible from the first attempt (but not on the same day).
Exclusion criteria
* Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6-weeks of Visit 1. * Patients who have ever required intubation for a severe asthma attack/exacerbation. * Patients who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study. * Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered. * Patients who have had a respiratory tract infection or asthma worsening as determined by investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 99. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening. * Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis. * Patients with severe narcolepsy and/or insomnia * Pregnant or nursing (lactating) women * Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 30 days after stopping of investigational medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) | Up to 52 Weeks | An adverse event (AE) was any untoward medical occurrence (example; any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study until the end of study visit. TEAEs were defined as adverse events started on or after the time of the first inhalation of study drug but no later than 7 days after the last administration (30 days in the case of SAEs). SAE was defined as any adverse event (appearance of \[or worsening of any pre-existing\]) undesirable sign, symptom or medical conditions which is fatal or life-threatening or results in persistent or significant disability/incapacity or constitutes a congenital anomaly/birth defect or requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52 | Baseline (Pre-dose), Week 26, Week 52 | Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry. Change from baseline in FVC at week 26 and 52 was reported. |
| Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks | Baseline up to week 52 | PEF is the peak expiratory flow, the maximum speed of expiration. Electronic peak flow meter (ePEF) was given to each participant at visit 1 for the measurement of morning and evening PEF. Change from baseline in morning and evening PEF over 52 weeks was measured. |
| Change From Baseline (Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 26 and 52 | Baseline (Pre-dose), Week 26, Week 52 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Change from baseline in FEV1 at week 26 and 52 was reported. |
| Proportion of Participants Who Achieved Clinically Meaningful Improvement Threshold in ACQ-7 Score (Decrease of Greater Than or Equal to 0.5 Units in ACQ-7) at Week 26 and 52 | Week 26, Week 52 | ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. Questions were equally weighted and total score is mean of 7 items. A decrease from baseline of at least 0.5 units in ACQ-7 score was considered to be clinically meaningful improvement. The proportion of participants achieving the clinically meaningful improvement threshold in ACQ-7 score were reported at Week 26 and Week 52. |
| Change From Baseline in Daily Number of Puffs of Rescue Medication Over 52 Weeks | Baseline up to week 52 | Daily use of rescue medication (number of puffs taken in the previous 12 hours) were recorded each morning and evening throughout the 52 week treatment by the participant using their electronic diary. |
| Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 26 and 52 | Baseline, Week 26, Week 52 | ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point Likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. The questions were equally weighted and the total score is the mean of the 7 items. A decrease of ACQ-7 score of at least 0.5 from baseline was considered to be clinically meaningful improvement. |
Countries
Japan
Participant flow
Pre-assignment details
A total of 161 participants were screened, of which 94 participants entered the treatment phase. A total of 86 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| QVM149 Participants received QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) 150/50/160 mcg once daily as powder in hard capsules via Concept1 inhaler in the evening throughout treatment epoch of 52 weeks. | 94 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participant/Guardian Decision | 7 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | QVM149 |
|---|---|
| Age, Continuous | 50.3 years STANDARD_DEVIATION 12.46 |
| Body Mass Index (BMI) | 25.29 Kilograms per meter square (kg/m^2) STANDARD_DEVIATION 4.554 |
| Height | 164.17 Centimeters (cm) STANDARD_DEVIATION 8.495 |
| Race/Ethnicity, Customized East Asian | 94 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 94 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 50 Participants |
| Weight | 68.31 Kilogram (kg) STANDARD_DEVIATION 14.044 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 94 |
| other Total, other adverse events | 57 / 94 |
| serious Total, serious adverse events | 6 / 94 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence (example; any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study until the end of study visit. TEAEs were defined as adverse events started on or after the time of the first inhalation of study drug but no later than 7 days after the last administration (30 days in the case of SAEs). SAE was defined as any adverse event (appearance of \[or worsening of any pre-existing\]) undesirable sign, symptom or medical conditions which is fatal or life-threatening or results in persistent or significant disability/incapacity or constitutes a congenital anomaly/birth defect or requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.
Time frame: Up to 52 Weeks
Population: Safety set included all participants who received at least one dose of study medication during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QVM149 | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) | TEAEs | 64 Participants |
| QVM149 | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) | SAEs | 6 Participants |
Secondary
Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 26 and 52
ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point Likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. The questions were equally weighted and the total score is the mean of the 7 items. A decrease of ACQ-7 score of at least 0.5 from baseline was considered to be clinically meaningful improvement.
Time frame: Baseline, Week 26, Week 52
Population: FAS included all participants who entered in the treatment epoch of this study and received at least one dose of study medication during the study. Here, 'n' (number analyzed) signified number of participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 | Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 26 and 52 | Week 26 | -0.881 Score on a scale | Standard Deviation 0.5629 |
| QVM149 | Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 26 and 52 | Week 52 | -0.935 Score on a scale | Standard Deviation 0.6155 |
Secondary
Change From Baseline in Daily Number of Puffs of Rescue Medication Over 52 Weeks
Daily use of rescue medication (number of puffs taken in the previous 12 hours) were recorded each morning and evening throughout the 52 week treatment by the participant using their electronic diary.
Time frame: Baseline up to week 52
Population: FAS included all participants who entered in the treatment epoch of this study and received at least one dose of study medication during the study. Here 'N' (overall number of participants analyzed) signified number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QVM149 | Change From Baseline in Daily Number of Puffs of Rescue Medication Over 52 Weeks | -0.29 Number of puffs | Standard Deviation 0.895 |
Secondary
Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks
PEF is the peak expiratory flow, the maximum speed of expiration. Electronic peak flow meter (ePEF) was given to each participant at visit 1 for the measurement of morning and evening PEF. Change from baseline in morning and evening PEF over 52 weeks was measured.
Time frame: Baseline up to week 52
Population: FAS included all participants who entered in the treatment epoch of this study and received at least one dose of study medication during the study. Here, 'n' (number anlayzed) signified number of participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 | Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks | Morning | 42.26 liters per minute (L/min) | Standard Deviation 61.913 |
| QVM149 | Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks | Evening | 35.48 liters per minute (L/min) | Standard Deviation 60.71 |
Secondary
Change From Baseline (Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 26 and 52
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Change from baseline in FEV1 at week 26 and 52 was reported.
Time frame: Baseline (Pre-dose), Week 26, Week 52
Population: Full Analysis Set (FAS) included all participants who entered in the treatment epoch of this study and received at least one dose of study medication during the study. Here, 'n' (number analyzed) signified number of participants evaluable for specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 | Change From Baseline (Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 26 and 52 | Week 26 | 0.3789 Liters (L) | Standard Deviation 0.34896 |
| QVM149 | Change From Baseline (Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 26 and 52 | Week 52 | 0.3598 Liters (L) | Standard Deviation 0.38878 |
Secondary
Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52
Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry. Change from baseline in FVC at week 26 and 52 was reported.
Time frame: Baseline (Pre-dose), Week 26, Week 52
Population: FAS included all participants who entered in the treatment epoch of this study and received at least one dose of study medication during the study. Here, 'n' (number analyzed) signified number of participants evaluable for specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 | Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52 | Week 52 | 0.2860 L | Standard Deviation 0.42054 |
| QVM149 | Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52 | Week 26 | 0.2938 L | Standard Deviation 0.35997 |
Secondary
Proportion of Participants Who Achieved Clinically Meaningful Improvement Threshold in ACQ-7 Score (Decrease of Greater Than or Equal to 0.5 Units in ACQ-7) at Week 26 and 52
ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. Questions were equally weighted and total score is mean of 7 items. A decrease from baseline of at least 0.5 units in ACQ-7 score was considered to be clinically meaningful improvement. The proportion of participants achieving the clinically meaningful improvement threshold in ACQ-7 score were reported at Week 26 and Week 52.
Time frame: Week 26, Week 52
Population: Analysis population included FAS with ACQ-7 data at the respective visit. Here 'n' (number analyzed) signified number of participants evaluable for specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVM149 | Proportion of Participants Who Achieved Clinically Meaningful Improvement Threshold in ACQ-7 Score (Decrease of Greater Than or Equal to 0.5 Units in ACQ-7) at Week 26 and 52 | Week 26 | 67.4 Percentage of participants |
| QVM149 | Proportion of Participants Who Achieved Clinically Meaningful Improvement Threshold in ACQ-7 Score (Decrease of Greater Than or Equal to 0.5 Units in ACQ-7) at Week 26 and 52 | Week 52 | 73.8 Percentage of participants |