Trial Outcomes & Findings for A Long-term Safety Study of QVM149 in Japanese Patients With Asthma (NCT NCT03100825)

NCT ID: NCT03100825

Last Updated: 2020-04-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

96 participants

Primary outcome timeframe

Up to 52 Weeks

Results posted on

2020-04-07

Participant Flow

A total of 161 participants were screened, of which 94 participants entered the treatment phase. A total of 86 participants completed the study.

Participant milestones

Participant milestones
Measure
QVM149
Participants received QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) 150/50/160 micrograms (mcg) once daily as powder in hard capsules via Concept1 inhaler in the evening throughout treatment epoch of 52 weeks.
Overall Study
STARTED
94
Overall Study
COMPLETED
86
Overall Study
NOT COMPLETED
8

Reasons for withdrawal

Reasons for withdrawal
Measure
QVM149
Participants received QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) 150/50/160 micrograms (mcg) once daily as powder in hard capsules via Concept1 inhaler in the evening throughout treatment epoch of 52 weeks.
Overall Study
Participant/Guardian Decision
7
Overall Study
Physician Decision
1

Baseline Characteristics

A Long-term Safety Study of QVM149 in Japanese Patients With Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
QVM149
n=94 Participants
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.
Age, Continuous
50.3 years
STANDARD_DEVIATION 12.46 • n=5 Participants
Sex: Female, Male
Female
44 Participants
n=5 Participants
Sex: Female, Male
Male
50 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
94 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race/Ethnicity, Customized
East Asian
94 Participants
n=5 Participants
Height
164.17 Centimeters (cm)
STANDARD_DEVIATION 8.495 • n=5 Participants
Weight
68.31 Kilogram (kg)
STANDARD_DEVIATION 14.044 • n=5 Participants
Body Mass Index (BMI)
25.29 Kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 4.554 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 52 Weeks

Population: Safety set included all participants who received at least one dose of study medication during the study.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=94 Participants
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs)
TEAEs
64 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs)
SAEs
6 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=94 Participants
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.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=94 Participants
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.
Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52
Week 26
0.2938 L
Standard Deviation 0.35997
Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52
Week 52
0.2860 L
Standard Deviation 0.42054

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=94 Participants
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.
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
Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks
Evening
35.48 liters per minute (L/min)
Standard Deviation 60.710

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=94 Participants
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.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=89 Participants
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.
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
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
QVM149
n=93 Participants
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.
Change From Baseline in Daily Number of Puffs of Rescue Medication Over 52 Weeks
-0.29 Number of puffs
Standard Deviation 0.895

Adverse Events

QVM149

Serious events: 6 serious events
Other events: 57 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
QVM149
n=94 participants at risk
Participants received QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) 150/50/160 μg once daily in the evening throughout treatment epoch of 52 weeks.
Blood and lymphatic system disorders
Disseminated intravascular coagulation
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Eye disorders
Cataract
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Gastrointestinal disorders
Anal fistula
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Gastrointestinal disorders
Inguinal hernia
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Gastrointestinal disorders
Oesophageal rupture
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Appendicitis
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Lower respiratory tract infection
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyosarcoma
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Respiratory, thoracic and mediastinal disorders
Respiratory failure
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Vascular disorders
Hypotension
1.1%
1/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment

Other adverse events

Other adverse events
Measure
QVM149
n=94 participants at risk
Participants received QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) 150/50/160 μg once daily in the evening throughout treatment epoch of 52 weeks.
Gastrointestinal disorders
Gastrooesophageal reflux disease
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
General disorders
Pyrexia
3.2%
3/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Acute sinusitis
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Bronchitis
6.4%
6/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Cystitis
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Gastroenteritis
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Influenza
3.2%
3/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Nasopharyngitis
18.1%
17/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Pharyngitis
5.3%
5/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Rhinitis
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Infections and infestations
Upper respiratory tract infection
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Injury, poisoning and procedural complications
Contusion
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Metabolism and nutrition disorders
Diabetes mellitus
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Musculoskeletal and connective tissue disorders
Neck pain
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Musculoskeletal and connective tissue disorders
Trigger finger
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Nervous system disorders
Headache
3.2%
3/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Respiratory, thoracic and mediastinal disorders
Asthma
30.9%
29/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Respiratory, thoracic and mediastinal disorders
Dysphonia
10.6%
10/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
3.2%
3/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Skin and subcutaneous tissue disorders
Eczema
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment
Vascular disorders
Hypertension
2.1%
2/94 • From start of study treatment up to 52 Weeks
An Adverse Event (AE) any sign or symptom that occurs during the study treatment

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER