Trial Outcomes & Findings for TRIple in asthMA With uncontRolled pAtient on Medium streNgth of ICS + LABA (NCT NCT02676076)

Last Updated: 2026-06-26

Results Overview

Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment. FEV1=Forced expiratory volume in the first second

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1155 participants

Primary outcome timeframe

Week 0 (pre-treatment, baseline) to Week 26.

Results posted on

2026-06-26

Participant Flow

Overall, 1628 patients were screened according to inclusion and exclusion criteria; of these,1155 patients were randomised. Overall, 5 patients were randomised in error and did not start treatment (N=3 patients in the CHF 5993 pMDI 100/6/12.5 μg group and N=2 patients in the CHF 1535 pMDI 100/6 μg group). The data set Safety population, used for the evaluations represents 1150 patients.

Participant milestones

Participant milestones
Measure	CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB	CHF 1535 100/6 µg CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF
Overall Study STARTED	579	576
Overall Study COMPLETED	542	539
Overall Study NOT COMPLETED	37	37

Reasons for withdrawal

Reasons for withdrawal
Measure	CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB	CHF 1535 100/6 µg CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF
Overall Study Adverse event, serious fatal	3	0
Overall Study Asthma exacerbation	1	0
Overall Study Withdrawal by Subject	22	26
Overall Study Protocol Violation	7	4
Overall Study Adverse Event	0	5
Overall Study Lost to Follow-up	2	2
Overall Study Unknown Reason not specified	2	0

Baseline Characteristics

Row population differs from the 'Overall' number of subjects because only ex-smokers are considered for the baseline characteristic.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	Total n=1150 Participants Total of all reporting groups	CHF 5993 100/6/12.5 µg n=576 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
Age, Categorical <=18 years	0 Participants n=574 Participants	0 Participants n=1150 Participants	0 Participants n=576 Participants
Age, Categorical Between 18 and 65 years	476 Participants n=574 Participants	946 Participants n=1150 Participants	470 Participants n=576 Participants
Age, Categorical >=65 years	98 Participants n=574 Participants	204 Participants n=1150 Participants	106 Participants n=576 Participants
Age, Continuous	52.5 years STANDARD_DEVIATION 12.2 • n=574 Participants	52.5 years STANDARD_DEVIATION 12.3 • n=1150 Participants	52.6 years STANDARD_DEVIATION 12.4 • n=576 Participants
Sex: Female, Male Female	353 Participants n=574 Participants	708 Participants n=1150 Participants	355 Participants n=576 Participants
Sex: Female, Male Male	221 Participants n=574 Participants	442 Participants n=1150 Participants	221 Participants n=576 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=574 Participants	0 Participants n=1150 Participants	0 Participants n=576 Participants
Race (NIH/OMB) Asian	0 Participants n=574 Participants	0 Participants n=1150 Participants	0 Participants n=576 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=574 Participants	0 Participants n=1150 Participants	0 Participants n=576 Participants
Race (NIH/OMB) Black or African American	0 Participants n=574 Participants	0 Participants n=1150 Participants	0 Participants n=576 Participants
Race (NIH/OMB) White	574 Participants n=574 Participants	1149 Participants n=1150 Participants	575 Participants n=576 Participants
Race (NIH/OMB) More than one race	0 Participants n=574 Participants	0 Participants n=1150 Participants	0 Participants n=576 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=574 Participants	1 Participants n=1150 Participants	1 Participants n=576 Participants
Body mass index	27.92 kg/m^2 STANDARD_DEVIATION 5.07 • n=574 Participants	27.94 kg/m^2 STANDARD_DEVIATION 4.94 • n=1150 Participants	27.95 kg/m^2 STANDARD_DEVIATION 4.81 • n=576 Participants
Body mass index - subgroups < 25 kg/m^2	173 Participants n=574 Participants	345 Participants n=1150 Participants	172 Participants n=576 Participants
Body mass index - subgroups ≥ 25 to < 30 kg/m^2	231 Participants n=574 Participants	462 Participants n=1150 Participants	231 Participants n=576 Participants
Body mass index - subgroups ≥ 30 kg/m^2	170 Participants n=574 Participants	343 Participants n=1150 Participants	173 Participants n=576 Participants
Number of pack-years	4.8 pack-years STANDARD_DEVIATION 2.5 • n=574 Participants	4.4 pack-years STANDARD_DEVIATION 2.4 • n=1150 Participants	4.1 pack-years STANDARD_DEVIATION 2.4 • n=576 Participants
Duration of asthma disease	25.2 years STANDARD_DEVIATION 12.8 • n=574 Participants	25.0 years STANDARD_DEVIATION 12.8 • n=1150 Participants	24.8 years STANDARD_DEVIATION 12.9 • n=576 Participants
Duration of asthma disease by group < 5 years	29 Participants n=574 Participants	61 Participants n=1150 Participants	32 Participants n=576 Participants
Duration of asthma disease by group 5-20 years	182 Participants n=574 Participants	358 Participants n=1150 Participants	176 Participants n=576 Participants
Duration of asthma disease by group ≥ 20 years	363 Participants n=574 Participants	731 Participants n=1150 Participants	368 Participants n=576 Participants
Number of asthma exacerbations in the previous year	1.2 asthma exacerbations STANDARD_DEVIATION 0.4 • n=574 Participants	1.2 asthma exacerbations STANDARD_DEVIATION 0.4 • n=1150 Participants	1.2 asthma exacerbations STANDARD_DEVIATION 0.4 • n=576 Participants
Time since last documented asthma exacerbation	5.83 months STANDARD_DEVIATION 2.54 • n=574 Participants	5.81 months STANDARD_DEVIATION 2.57 • n=1150 Participants	5.78 months STANDARD_DEVIATION 2.60 • n=576 Participants
Asthma medication at study entry Inhaled Corticosteroid(s) (ICS) / Long-Acting β2-Agonist (LABA); fixed combination	511 Participants n=574 Participants	1033 Participants n=1150 Participants	522 Participants n=576 Participants
Asthma medication at study entry Inhaled Corticosteroid(s) (ICS) + Long-Acting β2-Agonist (LABA); free combination	63 Participants n=574 Participants	117 Participants n=1150 Participants	54 Participants n=576 Participants
Use of spacer device before study entry YES	75 Participants n=574 Participants	151 Participants n=1150 Participants	76 Participants n=576 Participants
Use of spacer device before study entry NO	499 Participants n=574 Participants	999 Participants n=1150 Participants	500 Participants n=576 Participants
Smoking status at screening Ex-smoker	76 Participants n=574 Participants	168 Participants n=1150 Participants	92 Participants n=576 Participants
Smoking status at screening Non-smoker	498 Participants n=574 Participants	982 Participants n=1150 Participants	484 Participants n=576 Participants
Smoking duration	11.3 years STANDARD_DEVIATION 7.3 • n=76 Participants • Row population differs from the 'Overall' number of subjects because only ex-smokers are considered for the baseline characteristic.	11.3 years STANDARD_DEVIATION 7.6 • n=168 Participants • Row population differs from the 'Overall' number of subjects because only ex-smokers are considered for the baseline characteristic.	11.3 years STANDARD_DEVIATION 7.9 • n=92 Participants • Row population differs from the 'Overall' number of subjects because only ex-smokers are considered for the baseline characteristic.

PRIMARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 26.

Population: Intention to treat (ITT) population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline.

Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment. FEV1=Forced expiratory volume in the first second

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=553 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=557 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26	0.127 Liter Interval 0.098 to 0.157	0.185 Liter Interval 0.155 to 0.214

PRIMARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Population: ITT population: all randomised patients who receive at least one dose of the study treatment and with at least one available evaluation of efficacy (primary or secondary efficacy variables) after the baseline.

Asthma exacerbation (events): Moderate AND Severe. Severe: asthma worsening requiring initiation of treatment with systemic corticosteroids for at least 3 days (courses of corticosteroids separated by ≥1 week treated as separate severe exacerbations). Moderate: ≥1 of the following criteria fulfilled and leading to a change in treatment (sustained increase of ≥1 puff of short acting beta 2-agonist \[SABA\] for 2 consecutive days) as shown below: * Nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights/increase of ≥0.75 from baseline in daily symptom score on 2 consecutive days; increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase 4 puffs/day); * ≥20% decrease in peak expiratory flow from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline; * Visit to the ER/trial site for asthma treatment not requiring systemic corticosteroid.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period	2.157 events/year Interval 1.937 to 2.402	1.825 events/year Interval 1.634 to 2.037

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) and Week 26.

Peak FEV1 was analysed within 3 hours post-dose. FEV1=Peak of forced expiratory volume in the first second

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=553 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=553 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
3_Change From Baseline in Peak(0-3h) FEV1 at Week 26	0.401 Liter Interval 0.369 to 0.432	0.485 Liter Interval 0.453 to 0.516

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 26.

Change from baseline in the average morning PEF over the 26-Week treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=569 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=566 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment	-3.131 Liter/min Interval -6.533 to 0.271	5.325 Liter/min Interval 1.921 to 8.729

SECONDARY outcome

Timeframe: The entire treatment period; up to Week 52.

Severe Asthma Exacerbation Rate over the 52-Week Treatment Period in a pre-specified pooled analysis of 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=1145 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=1146 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis	0.310 events/year Interval 0.271 to 0.354	0.239 events/year Interval 0.206 to 0.276

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Change from baseline in peak FEV1 (within 3 h post-dosing) at all clinical visits. Baseline for pre-dose FEV1 was calculated as average of the FEV1 measurements (L) from the visit 2 (V2) Pre45min \& V2 Pre15min. If one of the two pre-dose values was missing, the baseline was equal to the available pre-dose value.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits Week 12	0.437 Liter Interval 0.406 to 0.467	0.499 Liter Interval 0.468 to 0.529
6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits Week 26	0.401 Liter Interval 0.369 to 0.432	0.485 Liter Interval 0.453 to 0.516
6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits Week 0	0.422 Liter Interval 0.397 to 0.448	0.475 Liter Interval 0.45 to 0.5
6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits Week 4	0.445 Liter Interval 0.415 to 0.474	0.520 Liter Interval 0.49 to 0.549
6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits Week 40	0.385 Liter Interval 0.353 to 0.417	0.477 Liter Interval 0.445 to 0.509
6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits Week 52	0.406 Liter Interval 0.373 to 0.439	0.472 Liter Interval 0.439 to 0.505

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in pre-dose FEV1 at all clinical visits.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits Week 40	0.130 Liter Interval 0.099 to 0.161	0.188 Liter Interval 0.157 to 0.219
7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits Week 52	0.158 Liter Interval 0.127 to 0.189	0.196 Liter Interval 0.165 to 0.227
7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits Week 26	0.127 Liter Interval 0.098 to 0.157	0.185 Liter Interval 0.155 to 0.214
7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits Week 4	0.147 Liter Interval 0.12 to 0.173	0.194 Liter Interval 0.168 to 0.221
7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits Week 12	0.166 Liter Interval 0.138 to 0.195	0.195 Liter Interval 0.167 to 0.224

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 26 and Week 52.

Results show the percentage of patients classified as FEV1 responders at both Week 26 and Week 52. FEV1 response: Change from baseline in pre-dose morning FEV1 ≥ 100 mL.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52 Week 26	258 Participants	309 Participants
8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52 Week 52	278 Participants	306 Participants

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Baseline definition: mean of two pre-dose FEV1 measurements at visit 2 (V2). Results show the change from baseline in FEV1 area under the curve \[AUC\] (0-3h) at all subsequent visits (i.e. change from baseline of the AUC of the serial post-dose spirometry assessments till 3h post-dose).

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits Week 4	0.351 Liter Interval 0.323 to 0.379	0.427 Liter Interval 0.399 to 0.455
9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits Week 12	0.354 Liter Interval 0.324 to 0.383	0.411 Liter Interval 0.381 to 0.44
9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits Week 0	0.316 Liter Interval 0.295 to 0.338	0.362 Liter Interval 0.341 to 0.384
9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits Week 26	0.314 Liter Interval 0.283 to 0.345	0.399 Liter Interval 0.368 to 0.43
9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits Week 40	0.301 Liter Interval 0.271 to 0.332	0.387 Liter Interval 0.356 to 0.418
9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits Week 52	0.324 Liter Interval 0.292 to 0.356	0.384 Liter Interval 0.352 to 0.416

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

ACQ-7 Questionnaire. Asthma Control Questionnaire-7 (ACQ-7) allows assessment of asthma control in individual patients. The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on lung function (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control (no impairment) and 6 indicating poor control (maximum impairment). 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 was completed by the study investigator using data from the Master Scope spirometer. Baseline for ACQ-7 was the total score recorded at Visit 2 (Week 0) of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. A negative change from baseline indicates improvement in lung function.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits Week 26	-0.584 score on a scale Interval -0.638 to -0.529	-0.627 score on a scale Interval -0.681 to -0.572
10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits Week 52	-0.722 score on a scale Interval -0.779 to -0.665	-0.745 score on a scale Interval -0.801 to -0.688
10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits Week 4	-0.453 score on a scale Interval -0.502 to -0.403	-0.502 score on a scale Interval -0.551 to -0.453
10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits Week 12	-0.576 score on a scale Interval -0.629 to -0.522	-0.592 score on a scale Interval -0.646 to -0.539
10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits Week 40	-0.627 score on a scale Interval -0.684 to -0.571	-0.672 score on a scale Interval -0.729 to -0.615

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 26 and Week 52

Asthma Control Questionnaire (ACQ) and Asthma Control Questionnaire-7 (QAC-7) are defined in the description of Outcome measure 10 above. An ACQ-7 response was defined as change from baseline (Week 0, pre-dose) in ACQ-7 score ≤ -0.5; non-response was defined as change from baseline in ACQ-7 score \>-0.5 or missing data. Results represent the responders (i.e. change from baseline in ACQ-7 Score ≤ -0.5) at Week 26 and Week 52.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52 Week 26	291 Participants	317 Participants
11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52 Week 52	340 Participants	350 Participants

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Change from baseline in average MORNING PEF (L/min) over 52 weeks of treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=569 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=566 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
12a_Change From Baseline in Average Morning PEF (L/Min) Over 52 Weeks of Treatment	-4.406 Liter/min Interval -8.242 to -0.571	5.845 Liter/min Interval 2.009 to 9.681

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 26 and Week 52.

Change from baseline in average EVENING PEF (L/min) over 26 and 52 weeks of treatment. PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
12b_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment Weeks 1-26	-5.502 Liter/min Interval -8.989 to -2.015	5.828 Liter/min Interval 2.33 to 9.327
12b_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment Weeks 1-52	-7.240 Liter/min Interval -11.048 to -3.433	5.440 Liter/min Interval 1.622 to 9.259

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Data were analysed for the number of patients at risk of a moderate or severe asthma exacerbation. Results show the number of patients who had moderate or severe asthma exacerbation over the 52 weeks treatment period.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
13_Number of Patients at Risk of Moderate or Severe Asthma Exacerbation Over 52 Weeks	379 Participants	337 Participants

SECONDARY outcome

Timeframe: Week 0 (Baseline) to 52 weeks for both studies in the pooled analysis.

Data were analysed for the number of patients at risk of a severe asthma exacerbation in the pooled analysis of the two pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of patients who had a severe asthma exacerbation over the 52 weeks treatment period. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=1145 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=1146 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
14_Number of Patients at Risk of Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02	257 Participants	209 Participants

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Moderate asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-055993AB2-02 (TRIGGER). The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=1145 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=1146 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
15_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02.	1.717 events/year Interval 1.577 to 1.869	1.515 events/year Interval 1.39 to 1.651

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=1145 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=1146 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
16_Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02	663 Participants	588 Participants

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Moderate and severe asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of participants with moderate and severe asthma exacerbation. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=1145 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=1146 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
17_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02	2.074 events/year Interval 1.92 to 2.241	1.788 events/year Interval 1.653 to 1.935

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Time to first moderate or severe asthma exacerbation in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER). Results show the number of participants with moderate or severe asthma exacerbation. The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=1145 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=1146 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
18_Number of Patients at Risk of Moderate OR Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02	743 Participants	660 Participants

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Moderate asthma exacerbation rate over the 52-Week treatment period.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
19_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period	1.821 events/year Interval 1.621 to 2.046	1.575 events/year Interval 1.399 to 1.773

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Data were analysed for the number of patients at risk of a MODERATE asthma exacerbation.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
20_Number of Patients at Risk of a MODERATE Asthma Exacerbation	343 Participants	305 Participants

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 26 and Week 52.

Change from baseline in the average use of rescue medication over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
21a_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods Weeks 1-26	-0.467 puffs/day Interval -0.532 to -0.402	-0.475 puffs/day Interval -0.54 to -0.41
21a_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods Weeks 1-52	-0.537 puffs/day Interval -0.603 to -0.471	-0.533 puffs/day Interval -0.599 to -0.467

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in the average use (puffs/day) of rescue medication in each inter-visit period. Data was collected through an electronic daily diary from screening to the end of the study.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period Visit 2 - Visit 3 Weeks 1-4	-0.372 puffs/day Standard Deviation 0.883	-0.340 puffs/day Standard Deviation 0.825
21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period Visit 3 - Visit 4 Weeks 5-12	-0.468 puffs/day Standard Deviation 1.079	-0.460 puffs/day Standard Deviation 0.998
21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period Visit 4 - Visit 5 Weeks 13-26	-0.527 puffs/day Standard Deviation 1.141	-0.494 puffs/day Standard Deviation 1.103
21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period Visit 5 - Visit 6 Weeks 27-40	-0.616 puffs/day Standard Deviation 1.230	-0.555 puffs/day Standard Deviation 1.132
21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period Visit 6 - Visit 7 Weeks 41-52	-0.625 puffs/day Standard Deviation 1.290	-0.617 puffs/day Standard Deviation 1.217

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Change from baseline in the percentage of rescue medication-free days in each inter-visit period over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
22a_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods Weeks 1-26	14.723 percentage of days Interval 12.674 to 16.772	14.702 percentage of days Interval 12.656 to 16.747
22a_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods Weeks 1-52	16.606 percentage of days Interval 14.519 to 18.693	16.377 percentage of days Interval 14.295 to 18.46

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in the percentage of rescue medication-free days in each inter-visit period over the entire treatment. Data was collected through an electronic daily diary from screening to the end of the study.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment Visit 4 - Visit 5 Weeks 13-26	16.664 percentage of days Standard Deviation 33.840	15.620 percentage of days Standard Deviation 31.061
22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment Visit 5 - Visit 6 Weeks 27-40	18.948 percentage of days Standard Deviation 35.215	16.908 percentage of days Standard Deviation 31.486
22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment Visit 2 - Visit 3 Weeks 1-4	10.986 percentage of days Standard Deviation 25.864	9.436 percentage of days Standard Deviation 23.342
22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment Visit 3 - Visit 4 Weeks 5-12	15.334 percentage of days Standard Deviation 30.671	14.146 percentage of days Standard Deviation 29.065
22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment Visit 6 - Visit 7 Weeks 41-52	19.408 percentage of days Standard Deviation 36.606	18.543 percentage of days Standard Deviation 32.486

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Data was collected through an electronic daily diary from screening to the end of the study. Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Weeks of treatment. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered: cough, wheeze, chest tightness, breathlessness. * Morning (night-time asthma symptom score): * 0 No symptoms; * 1 Mild = Symptoms not causing awakening; * 2 Moderate = Discomfort enough to cause awakenings; * 3 Severe = Causing awakenings for most of the night/did not sleep at all. * Evening (daytime asthma symptom score): * 0 No symptoms; * 1 Mild = Aware of symptoms, which could be easily tolerated; * 2 Moderate = Discomfort enough to cause interference with daily activity; * 3 Severe = Incapacitating

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
23a_Change From Baseline in the Average Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods Weeks 1-26	-0.166 score on a scale Interval -0.191 to -0.141	-0.161 score on a scale Interval -0.186 to -0.136
23a_Change From Baseline in the Average Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods Weeks 1-52	-0.194 score on a scale Interval -0.221 to -0.167	-0.180 score on a scale Interval -0.207 to -0.153

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in the average daily asthma symptom scores in each inter-visit period over the entire treatment. Data was collected daily through an electronic diary from screening to the end of the study. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered: cough, wheeze, chest tightness, breathlessness. * Morning (night-time asthma symptom score): * 0 No symptoms; * 1 Mild = Symptoms not causing awakening; * 2 Moderate = Discomfort enough to cause awakenings; * 3 Severe = Causing awakenings for most of the night/did not sleep at all. * Evening (daytime asthma symptom score): * 0 No symptoms; * 1 Mild = Aware of symptoms, which could be easily tolerated; * 2 Moderate = Discomfort enough to cause interference with daily activity; * 3 Severe = Incapacitating

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period Visit 3 - Visit 4 Weeks 5-12	-0.161 score on a scale Standard Deviation 0.349	-0.155 score on a scale Standard Deviation 0.317
23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period Visit 5 - Visit 6 Weeks 27-40	-0.222 score on a scale Standard Deviation 0.416	-0.194 score on a scale Standard Deviation 0.397
23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period Visit 2 - Visit 3 Weeks 1-4	-0.099 score on a scale Standard Deviation 0.275	-0.102 score on a scale Standard Deviation 0.252
23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period Visit 4 - Visit 5 Weeks 13-26	-0.195 score on a scale Standard Deviation 0.379	-0.178 score on a scale Standard Deviation 0.366
23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period Visit 6 - Visit 7 Weeks 41-52	-0.233 score on a scale Standard Deviation 0.435	-0.210 score on a scale Standard Deviation 0.419

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Change from baseline in the percentage of asthma symptom-free days over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Week treatment periods. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness. An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods Weeks 1-26	12.690 percentage of days Interval 10.623 to 14.757	14.204 percentage of days Interval 12.141 to 16.267
24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods Weeks 1-52	15.916 percentage of days Interval 13.615 to 18.217	16.847 percentage of days Interval 14.552 to 19.143

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in the percentage of asthma symptom-free days in each inter-visit periods over the entire treatment. Data was collected through an electronic daily diary from screening to end of the study. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness. An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23.

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods Visit 2 - Visit 3 Weeks 1-4	5.643 percentage of days Standard Deviation 18.612	6.753 percentage of days Standard Deviation 18.224
24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods Visit 3 - Visit 4 Weeks 5-12	11.378 percentage of days Standard Deviation 25.671	13.511 percentage of days Standard Deviation 26.291
24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods Visit 4 - Visit 5 Weeks 13-26	15.575 percentage of days Standard Deviation 30.808	16.937 percentage of days Standard Deviation 29.661
24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods Visit 5 - Visit 6 Weeks 27-40	17.918 percentage of days Standard Deviation 33.121	18.976 percentage of days Standard Deviation 33.106
24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods Visit 6 - Visit 7 Weeks 41-52	19.823 percentage of days Standard Deviation 35.464	20.512 percentage of days Standard Deviation 34.124

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in the percentage of asthma control days over the 26- and 52-Week treatment periods. Data was collected through an electronic daily diary from screening to the end of the study. Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness): Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all). Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity).

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
25a_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods Weeks 1-26	12.132 percentage of days Interval 10.102 to 14.162	13.890 percentage of days Interval 11.863 to 15.916
25a_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods Weeks 1-52	15.109 percentage of days Interval 12.863 to 17.355	16.395 percentage of days Interval 14.154 to 18.635

SECONDARY outcome

Timeframe: Week 0 (pre-treatment, baseline) to Week 52.

Results show the change from baseline in the percentage of asthma control days in each inter-visit period. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day. Data was collected through an electronic daily diary from screening to the end of the study Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness): Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all). Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity).

Outcome measures

Outcome measures
Measure	CHF 1535 100/6 µg n=574 Participants CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF	CHF 5993 100/6/12.5 µg n=575 Participants CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB
25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period Visit 2 - Visit 3 Weeks 1-4	5.754 percentage of days Standard Deviation 18.190	6.869 percentage of days Standard Deviation 18.066
25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period Visit 3 - Visit 4 Weeks 5-12	10.908 percentage of days Standard Deviation 25.058	13.212 percentage of days Standard Deviation 26.096
25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period Visit 4 - Visit 5 Weeks 13-26	14.794 percentage of days Standard Deviation 30.096	16.495 percentage of days Standard Deviation 29.096
25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period Visit 5 - Visit 6 Weeks 27-40	16.919 percentage of days Standard Deviation 32.002	18.522 percentage of days Standard Deviation 32.337
25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period Visit 6 - Visit 7 Weeks 41-52	18.823 percentage of days Standard Deviation 34.264	19.802 percentage of days Standard Deviation 33.330

Adverse Events

CHF 5993 100/6/12.5 µg

Serious events: 28 serious events

Other events: 429 other events

Deaths: 3 deaths

CHF 1535 100/6 µg

Serious events: 22 serious events

Other events: 451 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	CHF 5993 100/6/12.5 µg n=576 participants at risk CHF 5993 100/6/12.5 µg CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB	CHF 1535 100/6 µg n=574 participants at risk CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF
Investigations Blood pressure increased	2.1% 12/576 • Number of events 20 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	1.2% 7/574 • Number of events 14 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Vascular disorders Hypertension	2.8% 16/576 • Number of events 22 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	1.6% 9/574 • Number of events 12 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Nervous system disorders Headache	6.6% 38/576 • Number of events 49 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	8.0% 46/574 • Number of events 52 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	58.0% 334/576 • Number of events 1179 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	65.7% 377/574 • Number of events 1348 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.6% 9/576 • Number of events 9 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	2.1% 12/574 • Number of events 13 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	1.4% 8/576 • Number of events 8 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	2.4% 14/574 • Number of events 15 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	12.3% 71/576 • Number of events 85 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	13.6% 78/574 • Number of events 98 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection viral	2.6% 15/576 • Number of events 17 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	4.5% 26/574 • Number of events 30 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Bronchitis	3.1% 18/576 • Number of events 22 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	3.8% 22/574 • Number of events 26 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Pharyngitis	2.1% 12/576 • Number of events 12 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	2.8% 16/574 • Number of events 17 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Viral upper respiratory tract infection	2.1% 12/576 • Number of events 14 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	2.8% 16/574 • Number of events 20 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Rhinitis	1.4% 8/576 • Number of events 8 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	2.1% 12/574 • Number of events 13 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.
Infections and infestations Sinusitis	1.0% 6/576 • Number of events 6 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.	2.1% 12/574 • Number of events 12 • Adverse events (AE) were reported from the time of patient informed consent signature until study completion at week 52 or at study discontinuation. Treatment-emergent AEs (TEAEs) were defined as AEs with date of first randomised study treatment intake as AE onset date and date of completion/discontinuation. The Safety population was defined as all randomised patients who received at least one dose of study treatment.

Additional Information

Clinical Trial Transparency

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 to Chiesi before submission.
Publication restrictions are in place

Restriction type: OTHER