Trial Outcomes & Findings for Efficacy of LAMA Added to ICS in Treatment of Asthma (ELITRA) (NCT NCT02296411)

Results Overview

FEV1 = Forced Expiratory Volume in the first second AUC0-12h = area under the curve between time 0 and 12 hours; assessments were made at 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11.5h and 12h post-dose at Day 42 post-dose.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

98 participants

Primary outcome timeframe

Day 42

Results posted on

2026-04-22

Participant Flow

A total of 138 patients were screened, with 98 patients randomised to one of the following two treatment sequence groups: * CHF 5259 pMDI - placebo: n = 50 * Placebo - CHF 5259 pMDI: n = 48

Participant milestones

Participant milestones
Measure	CHF5259 pMDI - Placebo pMDI Sequence For this sequence, patients were treated in the first 6-weeks treatment period with two puffs of CHF 5259 pMDI 12.5 μg twice a day (b.i.d.), for total daily dose of CHF 5259 pMDI of 50 μg. In the second 6-weeks treatment period patients received matched placebo of CHF 5259 pMDI. Both CHF 5259 pMDI or matched placebo were administered to patients receiving the background ICS medication Qvar® pMDI 50 μg or 100 μg b.i.d., for a total daily dose ranging from 100 μg to 400 μg, which was maintained throughout the study, even during the 1-week wash out period between the two treatment periods.	Placebo pMDI - CHF 5259 pMDI For this sequence, patients were treated in the first 6-weeks treatment period with matched placebo of CHF 5259 pMDI. In the second 6-weeks treatment period patients received two puffs of CHF 5259 pMDI 12.5 μg twice a day (b.i.d.), for total daily dose of CHF 5259 pMDI of 50 μg. Both matched placebo and CHF 5259 pMDI were administered to patients receiving the background ICS medication Qvar® pMDI 50 μg or 100 μg b.i.d., for a total daily dose ranging from 100 μg to 400 μg, which was maintained throughout the study, even during the 1-week wash out period between the two treatment periods.
Overall Study STARTED	50	48
Overall Study COMPLETED	50	47
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	CHF5259 pMDI - Placebo pMDI Sequence For this sequence, patients were treated in the first 6-weeks treatment period with two puffs of CHF 5259 pMDI 12.5 μg twice a day (b.i.d.), for total daily dose of CHF 5259 pMDI of 50 μg. In the second 6-weeks treatment period patients received matched placebo of CHF 5259 pMDI. Both CHF 5259 pMDI or matched placebo were administered to patients receiving the background ICS medication Qvar® pMDI 50 μg or 100 μg b.i.d., for a total daily dose ranging from 100 μg to 400 μg, which was maintained throughout the study, even during the 1-week wash out period between the two treatment periods.	Placebo pMDI - CHF 5259 pMDI For this sequence, patients were treated in the first 6-weeks treatment period with matched placebo of CHF 5259 pMDI. In the second 6-weeks treatment period patients received two puffs of CHF 5259 pMDI 12.5 μg twice a day (b.i.d.), for total daily dose of CHF 5259 pMDI of 50 μg. Both matched placebo and CHF 5259 pMDI were administered to patients receiving the background ICS medication Qvar® pMDI 50 μg or 100 μg b.i.d., for a total daily dose ranging from 100 μg to 400 μg, which was maintained throughout the study, even during the 1-week wash out period between the two treatment periods.
Overall Study Protocol Violation	0	1

Baseline Characteristics

Efficacy of LAMA Added to ICS in Treatment of Asthma (ELITRA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence CHF 5259 pMDI - Placebo pMDI + Qvar n=50 Participants In this sequence patients received: * CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg * Qvar® pMDI 50 μg or100 μg: 1 week +2 days wash-out period where patients received Qvar® pMDI 50 μg or 100 μg b.i.d., for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. * Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg. CHF 5259 12.5 µg + Qvar: comparison of CHF 5259 versus placebo over 2 treatment periods of 6 weeks ± 2 days CHF 5259 placebo + Qvar: comparison of CHF5259 versus placebo over 2 treatment periods of 6 weeks ± 2 days	Sequence Placebo pMDI - CHF 5259 pMDI + Qvar n=48 Participants In this sequence patients received: * Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg. * Qvar® pMDI 50 μg or100 μg: 1 week +2 days wash-out period where patients received Qvar® pMDI 50 μg or 100 μg b.i.d., for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. * CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg. CHF 5259 12.5 µg + Qvar: comparison of CHF 5259 versus placebo over 2 treatment periods of 6 weeks ± 2 days CHF 5259 placebo + Qvar: comparison of CHF5259 versus placebo over 2 treatment periods of 6 weeks ± 2 days	Total n=98 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=60 Participants	44 Participants n=56 Participants	89 Participants n=116 Participants
Age, Categorical >=65 years	5 Participants n=60 Participants	4 Participants n=56 Participants	9 Participants n=116 Participants
Age, Continuous	48.8 years STANDARD_DEVIATION 14.0 • n=60 Participants	47.2 years STANDARD_DEVIATION 12.8 • n=56 Participants	48.0 years STANDARD_DEVIATION 13.4 • n=116 Participants
Sex: Female, Male Female	30 Participants n=60 Participants	31 Participants n=56 Participants	61 Participants n=116 Participants
Sex: Female, Male Male	20 Participants n=60 Participants	17 Participants n=56 Participants	37 Participants n=116 Participants
Region of Enrollment Netherlands	0 participants n=60 Participants	1 participants n=56 Participants	1 participants n=116 Participants
Region of Enrollment Poland	17 participants n=60 Participants	19 participants n=56 Participants	36 participants n=116 Participants
Region of Enrollment Italy	1 participants n=60 Participants	1 participants n=56 Participants	2 participants n=116 Participants
Region of Enrollment Bulgaria	18 participants n=60 Participants	19 participants n=56 Participants	37 participants n=116 Participants
Region of Enrollment Germany	14 participants n=60 Participants	8 participants n=56 Participants	22 participants n=116 Participants

PRIMARY outcome

Timeframe: Day 42

Population: Intention-to-Treat population (ITT): all randomised subjects who receive at least one dose of the study treatment and with at least one available evaluation of efficacy after the baseline. Patients included in the model are n=95 instead of N=97 for CHF5259 and n=96 instead of N=98 for placebo.

FEV1 = Forced Expiratory Volume in the first second AUC0-12h = area under the curve between time 0 and 12 hours; assessments were made at 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11.5h and 12h post-dose at Day 42 post-dose.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=96 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=95 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
FEV1 AUC0-12h Normalized by Time on Day 42 (ITT Population)	2.373 liters Standard Deviation 0.830	2.470 liters Standard Deviation 0.857

PRIMARY outcome

Timeframe: Day 42

Population: Per Protocol population: All patients from the ITT population without any major protocol violations (i.e. wrong inclusions, poor compliance, non-permitted medications) were included in the PP population.Patients included in the model are n=86 instead of N=92 for CHF5259 and n=82 instead of N=90 for placebo.

FEV1 = Forced Expiratory Volume in the first second AUC0-12h = area under the curve between time 0 and 12 hours; assessments were made at 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11.5h and 12h post-dose at Day 42 post-dose.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=82 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=86 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
FEV1 AUC0-12h Normalized by Time on Day 42 (PP Population)	2.365 liters Standard Deviation 0.827	2.480 liters Standard Deviation 0.849

SECONDARY outcome

Timeframe: Baseline and Day 42

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5259 and n=97 instead of N=98 for placebo.

The change from baseline to Day 42 in Forced Expiratory Volume in the first second (FEV1) peak is a key secondary variable.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in Peak FEV1 on Day 42 (ITT Population)	0.278 liters Standard Deviation 0.293	0.394 liters Standard Deviation 0.281

SECONDARY outcome

Timeframe: Baseline and Day 42

Population: Per protocol population: All patients from the ITT population without any major protocol violations (i.e. wrong inclusions, poor compliance, non-permitted medications) were included in the PP population. Patients included in the model were n=91 instead of N=97 for CHF5259 and n=89 instead of N=98 for placebo.

The change from baseline to Day 42 in Forced Expiratory Volume in the first second (FEV1) peak is a key secondary variable.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=89 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=91 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in Peak FEV1 on Day 42 (PP Population)	0.258 liters Standard Deviation 0.299	0.392 liters Standard Deviation 0.263

SECONDARY outcome

Timeframe: Day 1

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5257 and n=96 instead of N=98 for placebo.

FEV1 = Forced Expiratory Volume in the first second AUC0-12h = area under the curve between time 0 and 12 hours; assessments were made at 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11.5h and 12h post-dose on Day 1 post-dose.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=96 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
FEV1 AUC0-12h Normalized by Time on Day 1	2.356 liters Standard Deviation 0.835	2.482 liters Standard Deviation 0.862

SECONDARY outcome

Timeframe: Day 1

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5257 and n=97 instead of N=98 for placebo.

AUC0-3h =Area Under the Curve between time 0 and 3 hours. FEV1 was assessed at 15 min, 30 min, 45 min, 1h, 2h, 3h on day 1.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
FEV1 AUC0-3h Normalised by Time on Day 1	2.344 liters Standard Deviation 0.815	2.496 liters Standard Deviation 0.863

SECONDARY outcome

Timeframe: Day 42

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=96 instead of N=97 for CHF5257 and n=97 instead of N=98 for placebo.

AUC0-3h =Area Under the Curve between time 0 and 3 hours. FEV1 was measured at 15 min, 30 min, 45 min, 1h, 2h, 3h. on day 1 and on day 42

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=96 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
FEV1 AUC0-3h Normalised by Time on Day 42	2.357 liters Standard Deviation 0.839	2.498 liters Standard Deviation 0.870

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: ITT population: all randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5257 and n=97 instead of N=98 for placebo.

The peak FEV1 is determined as the maximum FEV1 value obtained between 15 minutes and 12 hours post-dose. The baseline value is the mean of the pre-dose measurement of FEV1 at Day 1 of each treatment period.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in Peak FEV1 on Day 1	0.286 liters Standard Deviation 0.237	0.384 liters Standard Deviation 0.248

SECONDARY outcome

Timeframe: Baseline and Day 42

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5259 and n= 97 instead of n=98 for placebo.

The pre-dose morning FEV1 is defined as the mean of the two measurements at 45 and 15 minutes predose.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in Pre-dose Morning Through FEV1 on Day 42	0.041 liters Standard Deviation 0.258	0.136 liters Standard Deviation 0.291

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5257, and n=97 instead of N=98 for placebo.

Baseline value is the average of the pre-dose measurements of FEV1 Percentage of Predicted Normal Value on Day 1 of each treatment period. FEV1 Percentage Predicted Normal values was measured at all post-dose Time Points (T15´: 15 min post-dose, T30´: 30 min post-dose, T45´: 45 min post-dose, T1H: 1 hour post-dose ,T2H: 2 hours post-dose, T2H: 3 hours post-dose,T4H: 4 hours post-dose ,T6H: 6 hours post-dose ,T8H: 8 hours post-dose, T11H30´: 11 hours and 30 minpost-dose, T12H: 12 hours post-dose). Hereunder only changes from baseline at 12h post-dose data are reported.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in FEV1 Percentage of Predicted Normal Value on Day 1	2.9 percentage of predicted FEV1 Standard Deviation 7.5	5.1 percentage of predicted FEV1 Standard Deviation 8.1

SECONDARY outcome

Timeframe: Baseline and Day 42

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=95 instead of N=97 for CHF5259, and n= 96 instead of N=98 for placebo.

Baseline value is the average of the pre-dose measurements of FEV1 Percentage of Predicted Normal Value on Day 1 of each treatment period. FEV1 Percentage Predicted Normal values was measured at all post-dose Time Points (T15´: 15 min post-dose, T30´: 30 min post-dose, T45´: 45 min post-dose, T1H: 1 hour post-dose ,T2H: 2 hours post-dose, T2H: 3 hours post-dose,T4H: 4 hours post-dose ,T6H: 6 hours post-dose ,T8H: 8 hours post-dose, T11H30´: 11 hours and 30 minpost-dose, T12H: 12 hours post-dose). Hereunder only changes from baseline at 12h post-dose data are reported.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=96 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=95 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in FEV1 Percentage of Predicted Normal Value on Day 42	2.9 percentage of predicted normal value Standard Deviation 8.5	5.8 percentage of predicted normal value Standard Deviation 8.9

SECONDARY outcome

Timeframe: Twice Daily during treatment periods (from V1 to V5)

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=96, morning and evening, instead of N=97 for CHF5259, and n=97, morning and evening, instead of N=98 for placebo

PEF = Peak Expiratory Flow. PEF was measured at home by patients using a portable e-peak flow meter (AM3 device). Patients were educated on the purpose and technique of PEF home monitoring and specific instructions for use were made available to them. During the run-in/wash-out and the two treatment periods (from V1 to V5), PEF was monitored twice daily, in the morning and in the evening, before the intake of the background medication or study medication. PEF was also assessed during the visits only for information purpose of the Investigator. During each measurement session, the patient performed 3 blows and data were recorded in the device. The average daily morning PEF is the mean value of all morning PEF measurements. The average daily evening PEF is the mean value of all evening PEF measurements. Please note: the average daily morning PEF and the average daily evening PEF during the treatment periods are reported.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=96 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Average Daily PEF (Morning and Evening) During Treatment Periods average daily morning	346.9 liters/min Standard Deviation 111.5	363.2 liters/min Standard Deviation 117.7
Average Daily PEF (Morning and Evening) During Treatment Periods average daily evening	355.5 liters/min Standard Deviation 110.5	372.4 liters/min Standard Deviation 117

SECONDARY outcome

Timeframe: During treatment periods (from V2 to V5), up to 6 weeks

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=96 (daytime and nighttime) instead of N=97 for CHF5259, and n=97 (daytime and nighttime) instead of N=98 for placebo.

Asthma symptoms (cough, wheeze, chest tightness and breathlessness) were scored, always before PEF measurements, twice daily - daytime and nighttime - as follows: Daytime asthma symptom score (ranging 0-3, where the lower the score the better the outcome): 0 = No symptom 1. = Mild: aware of symptoms which can be easily tolerated 2. = Moderate: discomfort causing interference with daily activity 3. = Severe: inability to work/make usual activity The average score of each symptom is the mean value of all measurements. Total average Daily Asthma Symptoms score daytime = Σ〖Cough daytime score + Wheeze daytime score + Chest Tightness daytime score * Breathlessness daytime score〗/ Number of days with available data. The sum of the four symptoms per day ranges from 0 (no symptoms) to 12 (maximum severity), and the average total score across days retains this range, reflecting mean symptom severity. A lower score indicates better symptom control.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=96 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Average Daily Asthma Symptoms (Daytime) During Treatment Periods	2.66 score on a scale Standard Deviation 1.84	2.62 score on a scale Standard Deviation 1.98

SECONDARY outcome

Timeframe: Daily during treatment periods (from V2 to V5)

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=96 instead of N=97 for CHF5259, and n=97 instead of N=98 for placebo.

Asthma symptoms (cough, wheeze, chest tightness and breathlessness) were scored, always before PEF measurements, twice daily - daytime and nighttime - as follows: Nighttime asthma symptom score (ranging 0-3, where the lower the score the better the outcome): 0 = No symptom 1. = Mild: symptoms not causing awakening 2. = Moderate: discomfort causing awakenings 3. = Severe: causing awakenings for most of the night / don't allow to sleep at all The average score of each symptom is the mean value of all measurements. Total average Daily Asthma Symptoms score nighttime = Σ〖Cough nighttime score + Wheeze nighttime score + Chest Tightness nighttime score + Breathlessness nighttime score〗/ Number of days with available data. The sum of the four symptoms per day ranges from 0 (no symptoms) to 12 (maximum severity), and the average total score across days retains this range, reflecting mean symptom severity. A lower score indicates better symptom control.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=96 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Average Daily Asthma Symptoms (Nighttime) During Treatment Periods	2.39 score on a scale Standard Deviation 2.0	2.35 score on a scale Standard Deviation 2.1

SECONDARY outcome

Timeframe: During the treatment periods (from V2 to V5)

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5259 and n=97 instead of N=98 for placebo.

An asthma control day is derived from patient diary data, and is defined as days on which the patient meets both of the following criteria: a total asthma symptom score (daytime + nighttime) of 0, indicating no symptoms such as cough, wheeze, chest tightness, or breathlessness, and no use of rescue medication during the day.The percentage of control days is calculated as the number of asthma control days / number of days with available data.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Percentage of Asthma Control Days During the Treatment Periods	19.4 percentage of days Standard Deviation 28.5	21.7 percentage of days Standard Deviation 32.3

SECONDARY outcome

Timeframe: During the treatment periods (from V2 to V5)

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5259 and n=97 instead of N=98 for placebo.

The average use of rescue medication is expressed as the number of puffs per day and the number of times per day. The most common rescue medication used is salbutamol: the number of salbutamol puffs and the number of times salbutamol is used were recorded in the electronic diary twice daily, in the morning and in the evening, before the PEF measurements. Hereunder the first parameter is reported.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Average Use of Rescue Medication (Number of Puffs/Day)	1.1 number of puffs/day Standard Deviation 1.5	1 number of puffs/day Standard Deviation 1.6

SECONDARY outcome

Timeframe: During the treatment periods (from V2 to V5)

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5259 and n=97 instead of N=98 for placebo.

The average use of rescue medication is expressed as the number of puffs per day and the number of times per day. The most common rescue medication used is salbutamol: the number of salbutamol puffs and the number of times salbutamol is used were recorded in the electronic diary twice daily, in the morning and in the evening, before the PEF measurements. Hereunder the second parameter is reported.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Average Use of Rescue Medication (Number of Times/Day)	0.9 number of times/day Standard Deviation 1.3	0.8 number of times/day Standard Deviation 1.4

SECONDARY outcome

Timeframe: Baseline and Day 42

Population: All randomised patients who received at least one dose of the study medication and with at least one available evaluation of efficacy after the baseline were included in the ITT population. Patients included in the model were n=97 for CHF5259 and n=97 instead of N=98 for placebo.

The ACQ is a validated questionnaire rating patient asthma control. It has a multidimensional construct assessing symptoms (5 questions-self-administered) and rescue bronchodilator use (1 question-self-administered), and FEV1% predicted (1 question answered by clinicians). For each of the 7 questions, possible answer could score from 0 (no impairment for symptoms and rescue use) to 6 (maximum impairment for symptoms and rescue use). The questions are equally weighted and the ACQ total score is the mean of the 7 questions and therefore between 0 (asthma totally controlled) and 6 (asthma severely uncontrolled).

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in Asthma Control Questionnaire (ACQ) Total Score on Day 42	-0.17 score on a scale Standard Deviation 0.56	-0.39 score on a scale Standard Deviation 0.59

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: Intention-to-Treat population (ITT): all randomised subjects who receive at least one dose of the study treatment and with at least one available evaluation of efficacy after the baseline. Patients included in the model were n=97 for CHF5259 and n= 97 instead of N=98 for placebo.

FVC = Forced Vital Capacity. FVC was measured at 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11.5h and 12h post-dose at both days. The baseline value is the mean of the pre-dose measurement of FVC at Day 1 of each treatment period. Only changes from baseline at 12h post-dose data are reported hereunder.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=97 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=97 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in FVC on Day 1	0.114 liters Standard Deviation 0.319	0.105 liters Standard Deviation 0.348

SECONDARY outcome

Timeframe: Baseline and Day 42

Population: Intention-to-Treat population (ITT): all randomised subjects who receive at least one dose of the study treatment and with at least one available evaluation of efficacy after the baseline. Patients included in the model were n=95 instead of N=97 for CHF5259 and n= 96 instead of N=98 for placebo.

FVC = Forced Vital Capacity. FVC was measured at 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11.5h and 12h post-dose at both days. The baseline value is the mean of the pre-dose measurement of FVC at Day 1 of each treatment period. Only changes from baseline at 12h post-dose data are reported hereunder.

Outcome measures

Outcome measures
Measure	Placebo pMDI - ITT n=96 Participants Matched placebo of CHF 5259 pMDI via Metered dose inhalation of pressurised solution using a standard actuator. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.	CHF5259 pMDI - ITT n=95 Participants CHF 5259 pMDI 12.5 µg: two puffs twice a day (bid), for a total daily dose of CHF 5259 pMDI of 50 μg. Mode of administration: Metered dose inhalation of pressurised solution using a standard actuator. Treatment duration: 6 weeks ±2 days. Plus Qvar® pMDI 50 μg or 100 μg b.i.d. as a background therapy, for total daily dose of Qvar® pMDI ranged from 100 μg to 400 μg.
Change From Baseline in FVC on Day 42	0.068 liters Standard Deviation 0.346	0.096 liters Standard Deviation 0.34

Adverse Events

Run-in and Randomized CHF5259 pMDI (Safety Population)

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Run-in and Randomized Placebo pMDI (Safety Population)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Clinical Trial INFO

Chiesi Farmaceutici S.p.A.

Phone: +39 0521 2791

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 before submission. Data from individual study sites must not be published separately.
Publication restrictions are in place

Restriction type: OTHER