Trial Outcomes & Findings for A Long-term Safety Study of QMF149 in Japanese Participants With Asthma (NCT NCT03100500)

Results Overview

A TEAE is any adverse event that started on or after the time of the first inhalation of study drug but not later than 7 days (30 days in the case of a SAE) after the last administration. A SAE is described as any adverse event that leads to death, is life-threatening, results in persistent or significant disability/incapacity, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event which is medically significant.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

51 participants

Primary outcome timeframe

Up to 52 weeks

Results posted on

2020-02-07

Participant Flow

Participant milestones

Participant milestones
Measure	QMF-149 150/320 μg QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Overall Study STARTED	51
Overall Study COMPLETED	51
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Long-term Safety Study of QMF149 in Japanese Participants With Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Age, Continuous	51.9 years STANDARD_DEVIATION 12.45 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants
Race/Ethnicity, Customized Asian	51 Participants n=5 Participants
Race/Ethnicity, Customized East Asian	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: Safety Set consisted of all participants who received at least one dose of study medication during this study.

A TEAE is any adverse event that started on or after the time of the first inhalation of study drug but not later than 7 days (30 days in the case of a SAE) after the last administration. A SAE is described as any adverse event that leads to death, is life-threatening, results in persistent or significant disability/incapacity, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event which is medically significant.

Outcome measures

Outcome measures
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	40 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 26 and 52

Population: Full Analysis Set (FAS) consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective day are included.

The pre-dose FEV1 was defined as the mean of the pre-dose 45 and 15 min FEV1 values prior to evening dose. 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. A positive change from baseline in FEV1 indicates improvement in lung function.

Outcome measures

Outcome measures
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Change From Baseline of Pre-Dose Forced Expiratory Volume in 1 Second (FEV1) Measured After 26 And 52 Weeks Treatment Baseline	2.1565 liters (L) Standard Deviation 0.58074
Change From Baseline of Pre-Dose Forced Expiratory Volume in 1 Second (FEV1) Measured After 26 And 52 Weeks Treatment Change at Week 26	0.2417 liters (L) Standard Deviation 0.26361
Change From Baseline of Pre-Dose Forced Expiratory Volume in 1 Second (FEV1) Measured After 26 And 52 Weeks Treatment Change at Week 52	0.1827 liters (L) Standard Deviation 0.26627

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective post baseline month are included.

PEF is the greatest airflow rate achieved during forced exhalation with lungs fully inflated. PEF was analyzed separately in the morning and evening using an electronic Peak Flow Meter (ePEF). A positive change from baseline in PEF indicates improvement in lung function.

Outcome measures

Outcome measures
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Change From Baseline of Morning and Evening Peak Expiratory Flow (PEF) During 52 Weeks Treatment Change through Weeks 1-52, Evening PEF	9.34 liters/minute (L/min) Standard Deviation 42.685
Change From Baseline of Morning and Evening Peak Expiratory Flow (PEF) During 52 Weeks Treatment Baseline, Morning PEF	342.88 liters/minute (L/min) Standard Deviation 94.656
Change From Baseline of Morning and Evening Peak Expiratory Flow (PEF) During 52 Weeks Treatment Change through Weeks 1-52, Morning PEF	15.49 liters/minute (L/min) Standard Deviation 49.089
Change From Baseline of Morning and Evening Peak Expiratory Flow (PEF) During 52 Weeks Treatment Baseline, Evening PEF	352.65 liters/minute (L/min) Standard Deviation 92.624

SECONDARY outcome

Timeframe: Baseline, Weeks 26 and 52

Population: FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective day are included.

The ACQ-7 is a seven-item disease-specific instrument developed and validated to assess asthma control in participants. It consists of five items to assess symptoms and activity limitations, one question to assess rescue medication use, and one question to assess airway caliber (FEV1% predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. 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 (question 7) was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.

Outcome measures

Outcome measures
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Change From Baseline of Asthma Control Questionnaire (ACQ-7) After 26 And 52 Weeks Treatment Baseline	1.983 score on a scale Standard Deviation 0.5381
Change From Baseline of Asthma Control Questionnaire (ACQ-7) After 26 And 52 Weeks Treatment Change at Week 26	-0.689 score on a scale Standard Deviation 0.6268
Change From Baseline of Asthma Control Questionnaire (ACQ-7) After 26 And 52 Weeks Treatment Change at Week 52	-0.830 score on a scale Standard Deviation 0.6852

SECONDARY outcome

Timeframe: Weeks 26 and 52

Population: FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Number analyzed indicates the number of participants with data available for analysis at Weeks 26 and 52.

The ACQ-7 is a seven-item disease-specific instrument developed and validated to assess asthma control in participants. It consists of five items to assess symptoms and activity limitations, one question to assess rescue medication use, and one question to assess airway caliber (FEV1% predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. 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 (question 7) was completed by the study investigator using data from the Master Scope spirometer. The proportion of participants who achieved an improvement of at least 0.5 in ACQ-7 (i.e. decrease of ACQ-7 score of at least 0.5 from baseline) at post-baseline visits were analyzed.

Outcome measures

Outcome measures
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Responder Rate of Participants Achieving the Minimal Important Difference (MID) of ACQ-7 ≥ 0.5 After 26 And 52 Weeks Treatment Week 26	66.0 percentage of participants
Responder Rate of Participants Achieving the Minimal Important Difference (MID) of ACQ-7 ≥ 0.5 After 26 And 52 Weeks Treatment Week 52	72.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective post baseline month are included.

Based on the electronic-diary data, the total number of puffs of rescue medication per day over the 52 weeks were calculated and divided by the total number of days to derive the mean daily number of puffs of rescue medication taken for the participant.

Outcome measures

Outcome measures
Measure	QMF-149 150/320 μg n=51 Participants QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Change From Baseline of Rescue Medication Use During 52 Weeks Treatment Baseline	0.56 puffs/day Standard Deviation 1.382
Change From Baseline of Rescue Medication Use During 52 Weeks Treatment Change through Weeks 1-52	-0.18 puffs/day Standard Deviation 0.499

Adverse Events

QMF149 150/320 µg

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	QMF149 150/320 µg n=51 participants at risk QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Gastrointestinal disorders Gastritis	3.9% 2/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Bronchitis	11.8% 6/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Nasopharyngitis	29.4% 15/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Otitis media	3.9% 2/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Pharyngitis	3.9% 2/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Upper respiratory tract infection bacterial	5.9% 3/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Investigations Electrocardiogram QT prolonged	3.9% 2/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Musculoskeletal and connective tissue disorders Back pain	5.9% 3/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Musculoskeletal and connective tissue disorders Myalgia	5.9% 3/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Respiratory, thoracic and mediastinal disorders Asthma	54.9% 28/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.9% 2/51 • Up to 52 weeks Safety Set consisted of all participants who received at least one dose of study medication during this study.

Additional Information

Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER