Clinical Trial Results:
A phase II, multinational, multicentre, double blind, double dummy, randomised, cross-over, active - and placebo-controlled clinical study to compare the bronchodilator effect of single administration of CHF 1535 pMDI (fixed combination of extrafine beclomethasone dipropionate 50 μg + formoterol fumarate 6 μg/metered dose, total dose 100/12 μg) given with spacer vs. free combination of licensed extrafine beclomethasone dipropionate pMDI given with spacer (total dose 100 μg) plus formoterol pMDI given with spacer (total dose 12 μg) in terms of FEV1 AUC0-12h in asthmatic children
Summary
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EudraCT number |
2011-002060-24 |
Trial protocol |
PL Outside EU/EEA |
Global end of trial date |
26 Feb 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jul 2016
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First version publication date |
09 Aug 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CCD-0903-PR-0060
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01584492 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Chiesi Farmaceutici SpA
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Sponsor organisation address |
Via Palermo 26/A, Parma, Italy, 43122
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Public contact |
Clinical Trial Transparency Manager, Chiesi Farmaceutici SpA, clinicalTrials_info@chiesi.com
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Scientific contact |
Clinical Trial Transparency Manager, Chiesi Farmaceutici SpA, clinicalTrials_info@chiesi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000548-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Feb 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Feb 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Feb 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate the non-inferiority in terms of bronchodilator effect of single administration of CHF 1535 50/6 pMDI (fixed combination of extrafine beclomethasone dipropionate 50 µg + formoterol fumarate 6 µg/metered dose, 2 inhalations, total dose 100/12 µg) given with spacer vs. free combination of extrafine beclomethasone dipropionate 50 µg/metered dose pMDI (2 inhalations, total dose 100 µg) given with spacer plus formoterol 6 µg/metered dose pMDI (2 inhalations, total dose 12 µg) given with spacer in terms of FEV1 AUC 0-12 hours corrected by time for the 12 hours study period in asthmatic children
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines and local law requirements . Other than routine care, no specific measures for protection of trial subjects were implemented.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Dec 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Ukraine: 39
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Country: Number of subjects enrolled |
Poland: 20
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Worldwide total number of subjects |
59
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
59
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 81 patients were screened, of whom 59 patients were randomised from eight sites. Twenty-two patients failed screening because they did not meet the inclusion criteria. 1-week ± 3 days run-in period was followed by five single-day randomised treatment periods separated by wash-out periods of 14±7 days. | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial by sequence (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Two matched placebos were provided to achieve a complete double-blind, double-dummy design. The canisters/actuators of CHF 1535 and FF pMDI were identical.
The randomisation list was provided to the labelling facility but was not available to patients, investigators, monitors or employees of the centre involved in the management of the trial before unblinding of the data, unless in case of emergency. The Sponsor’s clinical team was also blinded during the study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence A/B/C/D/E | ||||||||||||||||||||||||||||||||||||
Arm description |
- Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m.. Each patient will have 6 inhalations at each | ||||||||||||||||||||||||||||||||||||
Arm type |
experimental - active comparator - placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535 pMDI - formoterol pMDI + BDP pMDI - placebo pMDI
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate, formoterol fumarate, placebo
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A 1-week ± 3 days run-in period was followed by five single-day randomized treatment periods separated by wash-out periods of 14±7 days. A safety follow-up phone contact was made 7 ±3 days after the last treatment visit or premature discontinuation, for safety purposes.
During the run-in period and during the wash-out periods, patients were treated with BDP pMDI HFA 50 μg extrafine (Ventolair®, Teva), 1 inhalation twice daily (daily dose: BDP 100 μg) administered with AeroChamber Plus™ spacer device.
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Arm title
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Sequence B/C/D/E/A | ||||||||||||||||||||||||||||||||||||
Arm description |
- Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||
Arm type |
experimental - active comparator - placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535 pMDI - formoterol pMDI + BDP pMDI - placebo pMDI
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate, formoterol fumarate, placebo
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A 1-week ± 3 days run-in period was followed by five single-day randomized treatment periods separated by wash-out periods of 14±7 days. A safety follow-up phone contact was made 7 ±3 days after the last treatment visit or premature discontinuation, for safety purposes.
During the run-in period and during the wash-out periods, patients were treated with BDP pMDI HFA 50 μg extrafine (Ventolair®, Teva), 1 inhalation twice daily (daily dose: BDP 100 μg) administered with AeroChamber Plus™ spacer device.
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Arm title
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Sequence C/D/E/A/B | ||||||||||||||||||||||||||||||||||||
Arm description |
- Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||
Arm type |
experimental - active comparator - placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535 pMDI - formoterol pMDI + BDP pMDI - placebo pMDI
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate, formoterol fumarate, placebo
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A 1-week ± 3 days run-in period was followed by five single-day randomized treatment periods separated by wash-out periods of 14±7 days. A safety follow-up phone contact was made 7 ±3 days after the last treatment visit or premature discontinuation, for safety purposes.
During the run-in period and during the wash-out periods, patients were treated with BDP pMDI HFA 50 μg extrafine (Ventolair®, Teva), 1 inhalation twice daily (daily dose: BDP 100 μg) administered with AeroChamber Plus™ spacer device.
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Arm title
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Sequence D/E/A/B/C | ||||||||||||||||||||||||||||||||||||
Arm description |
- Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||
Arm type |
experimental - active comparator - placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535 pMDI - formoterol pMDI + BDP pMDI - placebo pMDI
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate, formoterol fumarate, placebo
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A 1-week ± 3 days run-in period was followed by five single-day randomized treatment periods separated by wash-out periods of 14±7 days. A safety follow-up phone contact was made 7 ±3 days after the last treatment visit or premature discontinuation, for safety purposes.
During the run-in period and during the wash-out periods, patients were treated with BDP pMDI HFA 50 μg extrafine (Ventolair®, Teva), 1 inhalation twice daily (daily dose: BDP 100 μg) administered with AeroChamber Plus™ spacer device.
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Arm title
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Sequence E/A/B/C/D | ||||||||||||||||||||||||||||||||||||
Arm description |
- Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||
Arm type |
experimental - active comparator - placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535 pMDI - formoterol pMDI + BDP pMDI - placebo pMDI
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate, formoterol fumarate, placebo
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A 1-week ± 3 days run-in period was followed by five single-day randomized treatment periods separated by wash-out periods of 14±7 days. A safety follow-up phone contact was made 7 ±3 days after the last treatment visit or premature discontinuation, for safety purposes.
During the run-in period and during the wash-out periods, patients were treated with BDP pMDI HFA 50 μg extrafine (Ventolair®, Teva), 1 inhalation twice daily (daily dose: BDP 100 μg) administered with AeroChamber Plus™ spacer device.
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Baseline characteristics reporting groups
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Reporting group title |
Sequence A/B/C/D/E
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Reporting group description |
- Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m.. Each patient will have 6 inhalations at each | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence B/C/D/E/A
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Reporting group description |
- Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence C/D/E/A/B
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Reporting group description |
- Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence D/E/A/B/C
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Reporting group description |
- Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence E/A/B/C/D
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Sequence A/B/C/D/E
|
||
Reporting group description |
- Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m.. Each patient will have 6 inhalations at each | ||
Reporting group title |
Sequence B/C/D/E/A
|
||
Reporting group description |
- Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||
Reporting group title |
Sequence C/D/E/A/B
|
||
Reporting group description |
- Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||
Reporting group title |
Sequence D/E/A/B/C
|
||
Reporting group description |
- Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||
Reporting group title |
Sequence E/A/B/C/D
|
||
Reporting group description |
- Treatment E (Ref): placebo pMDI with spacer, 6 inhalations in the morning at the clinic - Treatment A (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations - Treatment B (Exp): CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations - Treatment C (Exp): CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations - Treatment D (Ref): formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations Drug administration was done in the morning of each visit day at the clinic between 7.00 and 9.00 a.m. | ||
Subject analysis set title |
CHF 1535 50/6 μg - ITT
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All randomised patients who received at least one dose of study medication and with any post-dose efficacy evaluations for a given treatment period.
|
||
Subject analysis set title |
CHF 1535 100/12 μg - ITT
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All randomised patients who will receive at least one dose of study medication and with any post-dose efficacy evaluations for a given treatment period.
|
||
Subject analysis set title |
CHF 1535 200/24 μg - ITT
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All randomised patients who will receive at least one dose of study medication and with any post-dose efficacy evaluations for a given treatment period.
|
||
Subject analysis set title |
BDP 100 μg + FF 12 μg - ITT
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All randomised patients who will receive at least one dose of study medication and with any post-dose efficacy evaluations for a given treatment period.
|
||
Subject analysis set title |
Placebo - ITT
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All randomised patients who will receive at least one dose of study medication and with any post-dose efficacy evaluations for a given treatment period.
|
||
Subject analysis set title |
CHF 1535 50/6 μg - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised patients who took at least one dose of study medication.
|
||
Subject analysis set title |
CHF 1535 100/12 μg - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised patients who took at least one dose of study medication.
|
||
Subject analysis set title |
CHF 1535 200/24 μg - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised patients who took at least one dose of study medication.
|
||
Subject analysis set title |
BDP 100 μg + FF 12 μg - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised patients who took at least one dose of study medication.
|
||
Subject analysis set title |
Placebo - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised patients who took at least one dose of study medication.
|
|
|||||||||||||||||||||||||
End point title |
FEV1 AUC0-12h standardised by time | ||||||||||||||||||||||||
End point description |
FEV1 AUC corrected by time measured over 12 hours (10 min pre-dose and 10 min, 30 min, 1, 2, 4, 6, 8, 10, 12 hours postdose) following the morning dose of study medication.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
At each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
CHF1535 100/12 μg vs BDP 100 μg + FF 12 μg | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 100/12 μg - ITT v BDP 100 μg + FF 12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.909 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
-0.003
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.047 | ||||||||||||||||||||||||
upper limit |
0.042 | ||||||||||||||||||||||||
Statistical analysis title |
CHF 1535 50/6 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 50/6 μg - ITT v Placebo - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
115
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.048 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.045
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0 | ||||||||||||||||||||||||
upper limit |
0.089 | ||||||||||||||||||||||||
Statistical analysis title |
CHF 1535 100/12 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 100/12 μg - ITT v Placebo - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
114
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.076
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.032 | ||||||||||||||||||||||||
upper limit |
0.121 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 200/24 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 200/24 μg - ITT v Placebo - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
115
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.086
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.041 | ||||||||||||||||||||||||
upper limit |
0.131 | ||||||||||||||||||||||||
Statistical analysis title |
BDP 100 μg + FF 12 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v BDP 100 μg + FF 12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.079
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.034 | ||||||||||||||||||||||||
upper limit |
0.123 |
|
|||||||||||||||||||||||||
End point title |
Peak FEV1 | ||||||||||||||||||||||||
End point description |
Peak FEV1 is intended as the maximum value of the post-dose measurements during a 12 hour interval
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
CHF1535 100/12 μg vs BDP 100 μg + FF 12 μg | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 100/12 μg - ITT v BDP 100 μg + FF 12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.198 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.034
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.018 | ||||||||||||||||||||||||
upper limit |
0.086 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 50/6 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 50/6 μg - ITT v Placebo - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
115
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.16 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.037
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.015 | ||||||||||||||||||||||||
upper limit |
0.089 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 100/12 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v CHF 1535 100/12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
114
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.119
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.067 | ||||||||||||||||||||||||
upper limit |
0.171 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 200/24 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v CHF 1535 200/24 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
115
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.094
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.042 | ||||||||||||||||||||||||
upper limit |
0.146 | ||||||||||||||||||||||||
Statistical analysis title |
BDP 100 μg + FF 12 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v BDP 100 μg + FF 12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.085
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.033 | ||||||||||||||||||||||||
upper limit |
0.137 |
|
|||||||||||||||||||||||||
End point title |
FEV1 at 12 h post-dose | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
CHF1535 100/12 μg vs BDP 100 μg + FF 12 μg | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 100/12 μg - ITT v BDP 100 μg + FF 12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||||||
P-value |
= 0.24 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
-0.037
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.098 | ||||||||||||||||||||||||
upper limit |
0.025 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 50/6 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
CHF 1535 50/6 μg - ITT v Placebo - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
115
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.76 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
-0.009
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.071 | ||||||||||||||||||||||||
upper limit |
0.052 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 100/12 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v CHF 1535 100/12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
114
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.283 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.033
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.028 | ||||||||||||||||||||||||
upper limit |
0.094 | ||||||||||||||||||||||||
Statistical analysis title |
CHF1535 200/24 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v CHF 1535 200/24 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
115
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.013 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.078
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.017 | ||||||||||||||||||||||||
upper limit |
0.139 | ||||||||||||||||||||||||
Statistical analysis title |
BDP 100 μg + FF 12 μg vs placebo | ||||||||||||||||||||||||
Comparison groups |
Placebo - ITT v BDP 100 μg + FF 12 μg - ITT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.025 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||||||
Point estimate |
0.07
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.009 | ||||||||||||||||||||||||
upper limit |
0.131 |
|
|||||||||||||||||||||||||
End point title |
Pre-dose heart rate | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Post-dose heart rate | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
30 minutes post-dose at each clinic visit from Visit 2 to Visit 6
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Pre-dose systolic blood pressure | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Sitting systolic blood pressure at each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Post-dose systolic blood pressure | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
30 minutes post-dose, sitting systolic blood pressure at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Pre-dose distolic blood pressure | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Pre-dose, sitting diastolic blood pressure at each visit from Visit 1 (screening visit, run-in) to Visit 6 (from Visit 2 to Visit 6: treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Post-dose diastolic blood pressure | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
30 minutes post-dose, sitting diastolic blood pressure at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Pre-dose QTcF | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose at each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
30 min post-dose QTcF | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
30 minutes post-dose at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
1 hour post-dose QTcF | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
1 hour post-dose at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
2 hour QTcF | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
2 hours post-dose at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
6 hour post-dose QTcF | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
6 hours post-dose at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
12 hour post-dose QTcF | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
12 hours post-dose at each visit from Visit 2 to Visit 6 (treatment period).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
At each visit from Visit 1 (screening visit, run-in period) to Visit 6 (from Visit 2 to Visit 6: treatment period) to follow-up.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety population - CHF 1535 50/6 μg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
CHF 1535 50/6 administered via a pMDI with spacer, 1 inhalation (dose: BDP 50 μg/FF 6 μg) + placebo HFA pMDI with spacer, 5 inhalations. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety population - CHF 1535 100/12 μg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
CHF 1535 50/6 administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg/FF 12 μg) + placebo HFA pMDI with spacer, 4 inhalations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety population - CHF 1535 200/24 μg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
CHF 1535 50/6 (dose: BDP 200 μg/FF 24 μg) administered via a pMDI with spacer, 4 inhalations (dose: BDP 200 μg/FF 24 μg) + placebo HFA pMDI with spacer, 2 inhalations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety population - BDP 100 μg + FF 12 μg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Formoterol 6 μg HFA administered via a pMDI with spacer, 2 inhalations (dose: FF 12 μg) + extrafine BDP 50 μg, administered via a pMDI with spacer, 2 inhalations (dose: BDP 100 μg) + placebo HFA pMDI with spacer, 2 inhalations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety population - Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo pMDI with spacer, 6 inhalations in the morning at the clinic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
06 Jul 2012 |
This substantial amendment was introduced:
1. To modify the inclusion criterion n.6 about reversibility test at the screening visit lowering the positive threshold to 12% improvement with 200 μg salbutamol from pre-dose value instead of 15% in this children population under stable inhaled corticosteroid therapy;
2. To increase the time window between the 12-hour spirometry visits, and the relevant
tolerance, from 7±3 to 14±7 days, in order to improve the acceptability of the study by patients and their parents, and to better match the availability of study personnel at the sites;
3. To provide also parents/patients with instructions for cleaning of AeroChamber Plus™ spacers in case of delay in attending clinic visits;
4. To decrease the number of participating Countries, keeping the same number of involved investigational sites;
5. To update the planned study start and end;
6. To allow the concomitant treatment with leukotriene antagonists if taken at stable dose in the 4 weeks prior to study entry and to be continued at the same dose throughout all the study period;
7. To correct some typing errors. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |