Clinical Trial Results:
A multicentre, randomised, double-blind, active-controlled, 3-way cross-over study to evaluate the efficacy and safety of a free combination of 3 doses of CHF 5259 (glycopyrrolate) plus Foster® 100/6µg (fixed combination of beclomethasone dipropionate plus formoterol) in a metered dose inhaler for the treatment of patients with uncontrolled asthma under medium doses of inhaled corticosteroids plus long-acting β2-agonists
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
Summary
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EudraCT number |
2013-003043-36 |
Trial protocol |
DE GB HU IT PL BG |
Global end of trial date |
08 Mar 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jul 2016
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First version publication date |
28 Jul 2016
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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-1206-PR-0088
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02127866 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Chiesi Farmaceutici S.p.A.
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Sponsor organisation address |
Via Palermo 26/A, Parma, Italy, 43122
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Public contact |
Clinical Trial Transparency, CHIESI FARMACEUTICI S.p.A, clinicalTrials_info@chiesi.com
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Scientific contact |
Clinical Trial Transparency, CHIESI FARMACEUTICI S.p.A, ClinicalTrial_info@chiesi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Mar 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 Mar 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Mar 2015
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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 evaluate the efficacy of a free combination of CHF 5259 (glycopyrrolate bromide [GB]) at 3 dose levels plus Foster 100/6 µg (fixed combination of beclomethasone dipropionate [BDP] plus formoterol [FF]) in a pressurised metered dose inhaler by comparison with Foster 100/6 µg in terms of FEV1 AUC0-12h normalised by time on Day 42.
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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 |
Foster® 100/6µg (fixed combination of beclometasone dipropionate plus formoterol) administered via pMDI. | ||
Actual start date of recruitment |
11 Apr 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Poland: 62
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
Bulgaria: 48
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Country: Number of subjects enrolled |
Germany: 35
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Country: Number of subjects enrolled |
Hungary: 59
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Country: Number of subjects enrolled |
Italy: 5
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Worldwide total number of subjects |
211
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EEA total number of subjects |
211
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
186
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From 65 to 84 years |
25
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85 years and over |
0
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Recruitment
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Recruitment details |
This multinational study was conducted at 44 clinical sites (43 active) in 6 countries. The recruitment took place in: Bulgaria (10 sites) Germany (8 sites) Hungary (7 sites) Italy (5 sites: 4 active and 1 non-active) Poland (12 sites) UK (2 sites) | |||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 322 patients were screened, of whom 211 were randomised to one of the following treatment sequence groups: •Sequence A-C-B: n = 53; •Sequence B-D-C: n = 53; •Sequence C-A-D: n = 53; •Sequence D-B-A: n = 52. 201 (95.3%) patients completed the study. | |||||||||||||||||||||||||||||||||||
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 | |||||||||||||||||||||||||||||||||||
Blinding implementation details |
To maintain the blind during the treatment period, patients inhaled study medication from four identical white canisters daily, regardless of treatment regimen. The randomisation list was provided to the labelling facility but was not available to patients, investigators, monitors or employees of CROMSOURCE 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-C-B | |||||||||||||||||||||||||||||||||||
Arm description |
Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg; Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 5259 pMDI
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Investigational medicinal product code |
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Other name |
glycopyrronium bromide [GB]
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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 |
• Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg;
• Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg;
• Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg.
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Investigational medicinal product name |
Foster® 100/6 μg pMDI
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Investigational medicinal product code |
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Other name |
fixed dose combination [FDC] of beclometasone dipropionate [BDP] plus formoterol [FF]
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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 |
• Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg;
• Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg;
• Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg.
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Arm title
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Sequence B-D-C | |||||||||||||||||||||||||||||||||||
Arm description |
Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg; Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg. Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 5259 pMDI
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Investigational medicinal product code |
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Other name |
glycopyrronium bromide [GB]
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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 |
• Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg;
• Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg; or
• Treatment D: two puffs of CHF 5259 placebo BID (plus Foster alone).
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Investigational medicinal product name |
Foster® 100/6 μg pMDI
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Investigational medicinal product code |
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Other name |
fixed dose combination [FDC] of beclometasone dipropionate [BDP] plus formoterol [FF]
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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 |
• Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg;
• Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg.
• Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg.
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Arm title
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Sequence C-A-D | |||||||||||||||||||||||||||||||||||
Arm description |
Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg; Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 5259 pMDI
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Investigational medicinal product code |
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Other name |
glycopyrronium bromide [GB]
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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 |
• Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg;
• Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg; or
• Treatment D: two puffs of CHF 5259 placebo BID (plus Foster alone).
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Investigational medicinal product name |
Foster® 100/6 μg pMDI
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Investigational medicinal product code |
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Other name |
fixed dose combination [FDC] of beclometasone dipropionate [BDP] plus formoterol [FF]
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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 |
• Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg;
• Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg.
• Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg.
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Arm title
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Sequence D-B-A | |||||||||||||||||||||||||||||||||||
Arm description |
Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg; Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg; Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 5259 pMDI
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Investigational medicinal product code |
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Other name |
glycopyrronium bromide [GB]
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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 |
• Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg;
• Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg;
• Treatment D: two puffs of CHF 5259 placebo BID (plus Foster alone).
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Investigational medicinal product name |
Foster® 100/6 μg pMDI
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Investigational medicinal product code |
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Other name |
fixed dose combination [FDC] of beclometasone dipropionate [BDP] plus formoterol [FF]
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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 |
• Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg;
• Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg;
• Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg.
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Baseline characteristics reporting groups
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Reporting group title |
Sequence A-C-B
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Reporting group description |
Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg; Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence B-D-C
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Reporting group description |
Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg; Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg. Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence C-A-D
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Reporting group description |
Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg; Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence D-B-A
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Reporting group description |
Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg; Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg; Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sequence A-C-B
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Reporting group description |
Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg; Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg. | ||
Reporting group title |
Sequence B-D-C
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Reporting group description |
Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg; Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg. Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. | ||
Reporting group title |
Sequence C-A-D
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Reporting group description |
Treatment C: two puffs of CHF 5259 25 μg BID + two puffs of Foster® 100 /6 μg BID – total daily dose of CHF 5259 100 μg + Foster® 400 μg/24 μg. Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg; Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg. | ||
Reporting group title |
Sequence D-B-A
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Reporting group description |
Treatment D: two puffs of CHF 5259 placebo BID and two puffs of Foster® 100 μg/6 μg BID – total daily dose of Foster® 400 μg/24 μg; Treatment B: one puff of CHF 5259 25 μg BID + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 50 μg + Foster® 400 μg/24 μg; Treatment A: one puff of CHF 5259 12.5 μg twice a day (BID) + one puff of CHF 5259 placebo BID + two puffs of Foster® 100 μg/6 μg BID – total daily dose of CHF 5259 25 μg + Foster® 400 μg/24 μg. | ||
Subject analysis set title |
Treatment A - ITT population
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||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Intention-to-Treat (ITT) population: all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after the Baseline were included in the ITT population.
|
||
Subject analysis set title |
Treatment A - safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety population: all randomised patients who received at least one dose of study treatment were included in the safety population.
|
||
Subject analysis set title |
Treatment B - ITT population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Intention-to-Treat (ITT) population: all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after the Baseline were included in the ITT population.
|
||
Subject analysis set title |
Treatment B - safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety population: all randomised patients who received at least one dose of study treatment were included in the safety population.
|
||
Subject analysis set title |
Treatment C - ITT population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Intention-to-Treat (ITT) population: all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after the Baseline were included in the ITT population.
|
||
Subject analysis set title |
Treatment C - safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety population: all randomised patients who received at least one dose of study treatment were included in the safety population.
|
||
Subject analysis set title |
Treatment D - ITT population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Intention-to-Treat (ITT) population: all randomised patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after the Baseline were included in the ITT population.
|
||
Subject analysis set title |
Treatment D - safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety population: all randomised patients who received at least one dose of study treatment were included in the safety population.
|
|
|||||||||||||||||||||
End point title |
FEV1 AUC0-12h normalised by time on Day 42 | ||||||||||||||||||||
End point description |
AUC0-12= area under the curve between the time 0 and 12 hours.
Post-dose FEV1 on Day 42 of each treatment period was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake. The baseline FEV1 was the average FEV1 recorded on Day 1 at 45 and 10 minutes prior to study intake.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [1] - This is the actual number of patients on which the analysis was performed. [2] - This is the actual number of patients on which the analysis was performed. [3] - This is the actual number of patients on which the analysis was performed. [4] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [5] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.059
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.021 | ||||||||||||||||||||
upper limit |
0.096 | ||||||||||||||||||||
Notes [5] - FEV1 AUC0-12h normalized by time at Day 42 will be analysed using an ANCOVA model including treatment, period and patient as fixed effects and baseline (average of the FEV1 pre-dose measurements on Day 1 of each treatment period) as a covariate. The adjusted mean differences between each dose level of the free combination and Foster alone will be calculated with their simultaneous 95% confidence intervals (CIs) and p-values. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [6] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.084
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.047 | ||||||||||||||||||||
upper limit |
0.121 | ||||||||||||||||||||
Notes [6] - FEV1 AUC0-12h normalized by time at Day 42 will be analysed using an ANCOVA model including treatment, period and patient as fixed effects and baseline (average of the FEV1 pre-dose measurements on Day 1 of each treatment period) as a covariate. The adjusted mean differences between each dose level of the free combination and Foster alone will be calculated with their simultaneous 95% confidence intervals (CIs) and p-values. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [7] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.084
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.047 | ||||||||||||||||||||
upper limit |
0.121 | ||||||||||||||||||||
Notes [7] - FEV1 AUC0-12h normalized by time at Day 42 will be analysed using an ANCOVA model including treatment, period and patient as fixed effects and baseline (average of the FEV1 pre-dose measurements on Day 1 of each treatment period) as a covariate. The adjusted mean differences between each dose level of the free combination and Foster alone will be calculated with their simultaneous 95% confidence intervals (CIs) and p-values. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=299 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
299
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [8] | ||||||||||||||||||||
P-value |
= 0.113 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.025
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.006 | ||||||||||||||||||||
upper limit |
0.057 | ||||||||||||||||||||
Notes [8] - FEV1 AUC0-12h normalized by time at Day 42 will be analysed using an ANCOVA model including treatment, period and patient as fixed effects and baseline (average of the FEV1 pre-dose measurements on Day 1 of each treatment period) as a covariate. The adjusted mean differences between each higher dose of the free combination (Treatment B and Treatment C) and the lowest dose of the free combination (Treatment A) will be calculated with their simultaneous 95% CIs and p-values. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [9] | ||||||||||||||||||||
P-value |
= 0.106 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.026
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.006 | ||||||||||||||||||||
upper limit |
0.057 | ||||||||||||||||||||
Notes [9] - FEV1 AUC0-12h normalized by time at Day 42 will be analysed using an ANCOVA model including treatment, period and patient as fixed effects and baseline (average of the FEV1 pre-dose measurements on Day 1 of each treatment period) as a covariate. The adjusted mean differences between each higher dose of the free combination (Treatment B and Treatment C) and the lowest dose of the free combination (Treatment A) will be calculated with their simultaneous 95% CIs and p-values. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [10] | ||||||||||||||||||||
P-value |
= 0.983 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.031 | ||||||||||||||||||||
upper limit |
0.031 | ||||||||||||||||||||
Notes [10] - FEV1 AUC0-12h normalized by time at Day 42 will be analysed using an ANCOVA model including treatment, period and patient as fixed effects and baseline (average of the FEV1 pre-dose measurements on Day 1 of each treatment period) as a covariate. The adjusted mean differences between each higher dose of the free combination (Treatment B and Treatment C) and the lowest dose of the free combination (Treatment A) will be calculated with their simultaneous 95% CIs and p-values. |
|
|||||||||||||||||||||
End point title |
Change from baseline in peak FEV1 on Day 42 | ||||||||||||||||||||
End point description |
The maximum FEV1 value obtained between 15 minutes and 12 hours post-dose is the peak FEV1.
Post-dose FEV1 on Day 42 of each treatment period was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake.
Baseline is the average of the FEV1 pre-dose measurements on Day 1 of each period (recorded at 45 and 10 minuted prior to study drug intake).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [11] - This is the actual number of patients on which the analysis was performed. [12] - This is the actual number of patients on which the analysis was performed. [13] - This is the actual number of patients on which the analysis was performed. [14] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [15] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
least square mean difference | ||||||||||||||||||||
Point estimate |
0.06
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.022 | ||||||||||||||||||||
upper limit |
0.098 | ||||||||||||||||||||
Notes [15] - The key secondary efficacy variable (i.e. change from Baseline in peak FEV1 on Day 42) was analysed on both the ITT and the PP populations using the ANCOVA model described for the primary efficacy variable. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [16] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.091
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.054 | ||||||||||||||||||||
upper limit |
0.128 | ||||||||||||||||||||
Notes [16] - The key secondary efficacy variable (i.e. change from Baseline in peak FEV1 on Day 42) was analysed on both the ITT and the PP populations using the ANCOVA model described for the primary efficacy variable |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [17] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.076
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.038 | ||||||||||||||||||||
upper limit |
0.113 | ||||||||||||||||||||
Notes [17] - The key secondary efficacy variable (i.e. change from Baseline in peak FEV1 on Day 42) was analysed on both the ITT and the PP populations using the ANCOVA model described for the primary efficacy variable. |
|||||||||||||||||||||
Statistical analysis title |
treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [18] | ||||||||||||||||||||
P-value |
= 0.051 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.031
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0 | ||||||||||||||||||||
upper limit |
0.062 | ||||||||||||||||||||
Notes [18] - The key secondary efficacy variable (i.e. change from Baseline in peak FEV1 on Day 42) was analysed on both the ITT and the PP populations using the ANCOVA model described for the primary efficacy variable. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [19] | ||||||||||||||||||||
P-value |
= 0.32 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.016
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.015 | ||||||||||||||||||||
upper limit |
0.047 | ||||||||||||||||||||
Notes [19] - The key secondary efficacy variable (i.e. change from Baseline in peak FEV1 on Day 42) was analysed on both the ITT and the PP populations using the ANCOVA model described for the primary efficacy variable. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [20] | ||||||||||||||||||||
P-value |
= 0.332 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.015
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.046 | ||||||||||||||||||||
upper limit |
0.016 | ||||||||||||||||||||
Notes [20] - The key secondary efficacy variable (i.e. change from Baseline in peak FEV1 on Day 42) was analysed on both the ITT and the PP populations using the ANCOVA model described for the primary efficacy variable |
|
|||||||||||||||||||||
End point title |
FEV1 AUC0-3h normalised by time on Day 1 | ||||||||||||||||||||
End point description |
AUC0-3h = area under the curve between time 0 and 3 hours.
The pre-dose and post-dose lung function assessments were recorded under supervision at the following timings:
•Pre-dose FEV1 on Day 1 at 45 and 10 minutes prior to study drug intake (baseline FEV1);
•Post-dose FEV1 on Day 1 of each treatment period: at 15’; 30’; 45’; 1h; 2h; 3h post-study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [21] - This is the actual number of patients on which the analysis was performed. [22] - This is the actual number of patients on which the analysis was performed. [23] - This is the actual number of patients on which the analysis was performed. [24] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [25] | ||||||||||||||||||||
P-value |
= 0.002 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.049
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.019 | ||||||||||||||||||||
upper limit |
0.079 | ||||||||||||||||||||
Notes [25] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [26] | ||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.049
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.019 | ||||||||||||||||||||
upper limit |
0.079 | ||||||||||||||||||||
Notes [26] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [27] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.053
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.023 | ||||||||||||||||||||
upper limit |
0.083 | ||||||||||||||||||||
Notes [27] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [28] | ||||||||||||||||||||
P-value |
= 0.995 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.03 | ||||||||||||||||||||
upper limit |
0.03 | ||||||||||||||||||||
Notes [28] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [29] | ||||||||||||||||||||
P-value |
= 0.778 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.004
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.026 | ||||||||||||||||||||
upper limit |
0.034 | ||||||||||||||||||||
Notes [29] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [30] | ||||||||||||||||||||
P-value |
= 0.771 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.004
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.025 | ||||||||||||||||||||
upper limit |
0.034 | ||||||||||||||||||||
Notes [30] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates |
|
|||||||||||||||||||||
End point title |
FEV1 AUC0-3h normalised by time on Day 42 | ||||||||||||||||||||
End point description |
AUC0-3h = area under the curve between time 0 and 3 hours.
The pre-dose and post-dose lung function assessments were recorded under supervision at the following timings:
•Pre-dose FEV1 on Day 1 at 45 and 10 minutes prior to study drug intake (baseline FEV1);
•Post-dose FEV1 on Day 42 of each treatment period: at 15’; 30’; 45’; 1h; 2h; 3h post-study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [31] - This is the actual number of patients on which the analysis was performed. [32] - This is the actual number of patients on which the analysis was performed. [33] - This is the actual number of patients on which the analysis was performed. [34] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [35] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.056
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.024 | ||||||||||||||||||||
upper limit |
0.089 | ||||||||||||||||||||
Notes [35] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [36] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.092
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.06 | ||||||||||||||||||||
upper limit |
0.124 | ||||||||||||||||||||
Notes [36] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [37] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.089
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.057 | ||||||||||||||||||||
upper limit |
0.122 | ||||||||||||||||||||
Notes [37] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [38] | ||||||||||||||||||||
P-value |
= 0.029 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.036
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.004 | ||||||||||||||||||||
upper limit |
0.069 | ||||||||||||||||||||
Notes [38] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [39] | ||||||||||||||||||||
P-value |
= 0.044 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.033
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.001 | ||||||||||||||||||||
upper limit |
0.066 | ||||||||||||||||||||
Notes [39] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [40] | ||||||||||||||||||||
P-value |
= 0.859 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.003
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.035 | ||||||||||||||||||||
upper limit |
0.029 | ||||||||||||||||||||
Notes [40] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in FEV1 pre-dose on Day 14 | ||||||||||||||||||||
End point description |
The pre-dose morning FEV1 is defined as the mean of the two measurements at 45 and 10 minutes pre-dose.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [41] - This is the actual number of patients on which the analysis was performed. [42] - This is the actual number of patients on which the analysis was performed. [43] - This is the actual number of patients on which the analysis was performed. [44] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [45] | ||||||||||||||||||||
P-value |
= 0.168 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.031
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.013 | ||||||||||||||||||||
upper limit |
0.075 | ||||||||||||||||||||
Notes [45] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [46] | ||||||||||||||||||||
P-value |
= 0.016 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.053
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.01 | ||||||||||||||||||||
upper limit |
0.096 | ||||||||||||||||||||
Notes [46] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [47] | ||||||||||||||||||||
P-value |
= 0.058 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.042
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.001 | ||||||||||||||||||||
upper limit |
0.086 | ||||||||||||||||||||
Notes [47] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [48] | ||||||||||||||||||||
P-value |
= 0.315 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.022
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.021 | ||||||||||||||||||||
upper limit |
0.066 | ||||||||||||||||||||
Notes [48] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [49] | ||||||||||||||||||||
P-value |
= 0.607 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.011
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.032 | ||||||||||||||||||||
upper limit |
0.055 | ||||||||||||||||||||
Notes [49] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=310 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
310
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [50] | ||||||||||||||||||||
P-value |
= 0.621 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.011
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.054 | ||||||||||||||||||||
upper limit |
0.032 | ||||||||||||||||||||
Notes [50] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in FEV1 pre-dose on Day 42 | ||||||||||||||||||||
End point description |
The pre-dose morning FEV1 is defined as the mean of the two measurements at 45 and 10 minutes pre-dose.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [51] - This is the actual number of patients on which the analysis was performed. [52] - This is the actual number of patients on which the analysis was performed. [53] - This is the actual number of patients on which the analysis was performed. [54] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [55] | ||||||||||||||||||||
P-value |
= 0.484 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.015
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.027 | ||||||||||||||||||||
upper limit |
0.058 | ||||||||||||||||||||
Notes [55] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [56] | ||||||||||||||||||||
P-value |
= 0.005 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.06
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.018 | ||||||||||||||||||||
upper limit |
0.102 | ||||||||||||||||||||
Notes [56] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [57] | ||||||||||||||||||||
P-value |
= 0.016 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.052
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.01 | ||||||||||||||||||||
upper limit |
0.094 | ||||||||||||||||||||
Notes [57] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [58] | ||||||||||||||||||||
P-value |
= 0.038 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.045
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.002 | ||||||||||||||||||||
upper limit |
0.087 | ||||||||||||||||||||
Notes [58] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [59] | ||||||||||||||||||||
P-value |
= 0.087 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.037
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.005 | ||||||||||||||||||||
upper limit |
0.079 | ||||||||||||||||||||
Notes [59] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [60] | ||||||||||||||||||||
P-value |
= 0.709 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.008
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.05 | ||||||||||||||||||||
upper limit |
0.034 | ||||||||||||||||||||
Notes [60] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in through FEV1 at 12 h post-dose on Day 1 | ||||||||||||||||||||
End point description |
Trough FEV1 at 12 hours is determined as the average of the 11.5 and 12 hours post-dose FEV1 assessments. Baseline value is the mean of the pre-dose measurement of FEV1 at Day 1 of each treatment period recorded at 45 and 10 minutes prior to study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [61] - This is the actual number of patients on which the analysis was performed. [62] - This is the actual number of patients on which the analysis was performed. [63] - This is the actual number of patients on which the analysis was performed. [64] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=299 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
299
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [65] | ||||||||||||||||||||
P-value |
= 0.159 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.028
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.011 | ||||||||||||||||||||
upper limit |
0.067 | ||||||||||||||||||||
Notes [65] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [66] | ||||||||||||||||||||
P-value |
= 0.089 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.033
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.005 | ||||||||||||||||||||
upper limit |
0.072 | ||||||||||||||||||||
Notes [66] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [67] | ||||||||||||||||||||
P-value |
= 0.008 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.053
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.014 | ||||||||||||||||||||
upper limit |
0.091 | ||||||||||||||||||||
Notes [67] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [68] | ||||||||||||||||||||
P-value |
= 0.781 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.005
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.033 | ||||||||||||||||||||
upper limit |
0.044 | ||||||||||||||||||||
Notes [68] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [69] | ||||||||||||||||||||
P-value |
= 0.205 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.025
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.014 | ||||||||||||||||||||
upper limit |
0.063 | ||||||||||||||||||||
Notes [69] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [70] | ||||||||||||||||||||
P-value |
= 0.32 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.019
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.019 | ||||||||||||||||||||
upper limit |
0.057 | ||||||||||||||||||||
Notes [70] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in through FEV1 at 12 h post-dose on Day 42 | ||||||||||||||||||||
End point description |
Trough FEV1 at 12 hours is determined as the average of the 11.5 and 12 hours post-dose FEV1 assessments. Baseline value is the mean of the pre-dose measurement of FEV1 at Day 1 of each treatment period recorded at 45 and 10 minutes prior to study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [71] - This is the actual number of patients on which the analysis was performed. [72] - This is the actual number of patients on which the analysis was performed. [73] - This is the actual number of patients on which the analysis was performed. [74] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [75] | ||||||||||||||||||||
P-value |
= 0.015 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.046
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.009 | ||||||||||||||||||||
upper limit |
0.083 | ||||||||||||||||||||
Notes [75] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [76] | ||||||||||||||||||||
P-value |
= 0.008 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.05
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.013 | ||||||||||||||||||||
upper limit |
0.087 | ||||||||||||||||||||
Notes [76] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [77] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.068
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.031 | ||||||||||||||||||||
upper limit |
0.105 | ||||||||||||||||||||
Notes [77] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=299 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
299
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [78] | ||||||||||||||||||||
P-value |
= 0.832 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.004
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.033 | ||||||||||||||||||||
upper limit |
0.041 | ||||||||||||||||||||
Notes [78] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [79] | ||||||||||||||||||||
P-value |
= 0.234 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.022
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.015 | ||||||||||||||||||||
upper limit |
0.059 | ||||||||||||||||||||
Notes [79] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [80] | ||||||||||||||||||||
P-value |
= 0.328 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.018
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.018 | ||||||||||||||||||||
upper limit |
0.055 | ||||||||||||||||||||
Notes [80] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in peak FEV1 on Day 1 | ||||||||||||||||||||
End point description |
The peak FEV1 is the maximum FEV1 value obtained between 15 minutes and 12 hours post-dose.
Post-dose FEV1 on Day 1 of each treatment period was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake.
Baseline is the average of the FEV1 pre-dose measurements on Day 1 of each period (recorded at 45 and 10 minuted prior to study drug intake).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [81] - This is the actual number of patients on which the analysis was performed. [82] - This is the actual number of patients on which the analysis was performed. [83] - This is the actual number of patients on which the analysis was performed. [84] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [85] | ||||||||||||||||||||
P-value |
= 0.002 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.058
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.022 | ||||||||||||||||||||
upper limit |
0.094 | ||||||||||||||||||||
Notes [85] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [86] | ||||||||||||||||||||
P-value |
= 0.012 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.045
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.01 | ||||||||||||||||||||
upper limit |
0.081 | ||||||||||||||||||||
Notes [86] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [87] | ||||||||||||||||||||
P-value |
= 0.004 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.053
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.017 | ||||||||||||||||||||
upper limit |
0.088 | ||||||||||||||||||||
Notes [87] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [88] | ||||||||||||||||||||
P-value |
= 0.492 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.012
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.048 | ||||||||||||||||||||
upper limit |
0.023 | ||||||||||||||||||||
Notes [88] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a Cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [89] | ||||||||||||||||||||
P-value |
= 0.772 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.005
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.041 | ||||||||||||||||||||
upper limit |
0.03 | ||||||||||||||||||||
Notes [89] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and Baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [90] | ||||||||||||||||||||
P-value |
= 0.689 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.007
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.028 | ||||||||||||||||||||
upper limit |
0.042 | ||||||||||||||||||||
Notes [90] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
FEV1 AUC0-12h normalised by time on Day 1 | ||||||||||||||||||||
End point description |
AUC0-12h = area under the curve between time 0 and 12 hours.
Post-dose FEV1 on Day 1 of each treatment period was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake. The baseline FEV1 was the average FEV1 recorded on Day 1 at 45 and 10 minutes prior to study intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [91] - This is the actual number of patients on which the analysis was performed. [92] - This is the actual number of patients on which the analysis was performed. [93] - This is the actual number of patients on which the analysis was performed. [94] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=297 (subject analysis set) is an innate error of the EudraCT database system
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
297
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [95] | ||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.051
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.02 | ||||||||||||||||||||
upper limit |
0.082 | ||||||||||||||||||||
Notes [95] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=300 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
300
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [96] | ||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.052
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.021 | ||||||||||||||||||||
upper limit |
0.083 | ||||||||||||||||||||
Notes [96] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [97] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.065
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.034 | ||||||||||||||||||||
upper limit |
0.096 | ||||||||||||||||||||
Notes [97] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [98] | ||||||||||||||||||||
P-value |
= 0.972 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.001
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.03 | ||||||||||||||||||||
upper limit |
0.031 | ||||||||||||||||||||
Notes [98] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [99] | ||||||||||||||||||||
P-value |
= 0.375 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.014
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.017 | ||||||||||||||||||||
upper limit |
0.045 | ||||||||||||||||||||
Notes [99] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [100] | ||||||||||||||||||||
P-value |
= 0.389 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.013
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.017 | ||||||||||||||||||||
upper limit |
0.044 | ||||||||||||||||||||
Notes [100] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
FEV1 percentage of predicted normal value at each time point post-dose on Day 1 and mean changes from Baseline | ||||||||||||||||||||
End point description |
Baseline is the average of the pre-dose measurements of FEV1 Percentage of Predicted Normal Value.
Measurements were done: 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11h and 30 min, 12h post-dose on Day 1.
Only data about the change from baseline at the last timepoint (12h post-dose) of the Day 1 are reported in the database.
For the data about the other timepoints on Day 1 see pdf attached.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: FEV1 Change D1.pdf) Untitled (Filename: FEV1 Value D1.pdf) |
||||||||||||||||||||
Notes [101] - This is the actual number of patients on which the analysis was performed. [102] - This is the actual number of patients on which the analysis was performed. [103] - This is the actual number of patients on which the analysis was performed. [104] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
FEV1 percentage of predicted normal value at 2h post-dose on Day 14 and mean changes from Baseline | ||||||||||||||||||||
End point description |
Baseline is the average of the pre-dose measurements of FEV1 Percentage of Predicted Normal Value.
Measurements were done 2h post-dose on Day 14.
Only the change from baseline (not the actual value) is reported in the database. For the actual values on the same endpoint , please see the pdf attached.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: FEV1 Value D14.pdf) |
||||||||||||||||||||
Notes [105] - This is the actual number of patients on which the analysis was performed. [106] - This is the actual number of patients on which the analysis was performed. [107] - This is the actual number of patients on which the analysis was performed. [108] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
FEV1 percentage of predicted normal value at each time point post-dose on Day 42 and mean changes from Baseline | ||||||||||||||||||||
End point description |
Baseline is the average of the pre-dose measurements of FEV1 Percentage of Predicted Normal Value.
Measurements were done: 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h, 8h, 11h and 30 min, 12h post-dose on Day 42.
Only data about the change from baseline at the last timepoint (12h post-dose) of the Day 42 are reported in the database.
For the data about the other timepoints on Day 42, please see the pdf attached.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: FEV1 changes D42.pdf) Untitled (Filename: FEV1 Value D42.pdf) |
||||||||||||||||||||
Notes [109] - This is the actual number of patients on which the analysis was performed. [110] - This is the actual number of patients on which the analysis was performed. [111] - This is the actual number of patients on which the analysis was performed. [112] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
FEV1 at 2 hours post-dose on Day 14 | ||||||||||||||||||||
End point description |
Post dose FEV1 on Day 14 of each treatment period was recorded at 2h post-study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [113] - This is the actual number of patients on which the analysis was performed. [114] - This is the actual number of patients on which the analysis was performed. [115] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from baseline in FEV1 2 Hours Post-Dose on Day 14 | ||||||||||||||||||||
End point description |
Baseline is the average of the pre-dose measurements FEV1 measurements that were recorded at 45 and 10 minutes prior to study intake.
Post dose FEV1 on Day 14 of each treatment period was recorded at 2h post-study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [116] - This is the actual number of patients on which the analysis was performed. [117] - This is the actual number of patients on which the analysis was performed. [118] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Average daily morning PEF | ||||||||||||||||||||
End point description |
E-peakflow meter/e-diary was completed at home on a daily basis morning and evening (daily download of the e-peakflow meter/e-diary). During the two wash-out periods, only the compliance to the wash-out medication was collected.
During the run-in period and the three treatment periods, PEF (L/min) was monitored twice daily before the intake of the run-in medication or study medication. Morning measurements were done approximately between 7:00 am and 9:00 am and evening measurements approximately between 7:00 pm and 9:00 pm. An alarm reminded the patients to perform measurements. During each measurement session, the patient performed three blows and data were recorded in the device.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Daily during run-in and treatment periods.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [119] - This is the actual number of patients on which the analysis was performed. [120] - This is the actual number of patients on which the analysis was performed. [121] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [122] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
10.07
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
5.52 | ||||||||||||||||||||
upper limit |
14.63 | ||||||||||||||||||||
Notes [122] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [123] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
11.12
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
6.6 | ||||||||||||||||||||
upper limit |
15.64 | ||||||||||||||||||||
Notes [123] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [124] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
9.49
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
4.98 | ||||||||||||||||||||
upper limit |
14 | ||||||||||||||||||||
Notes [124] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [125] | ||||||||||||||||||||
P-value |
= 0.649 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
1.05
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-3.47 | ||||||||||||||||||||
upper limit |
5.57 | ||||||||||||||||||||
Notes [125] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [126] | ||||||||||||||||||||
P-value |
= 0.798 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.59
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-5.09 | ||||||||||||||||||||
upper limit |
3.92 | ||||||||||||||||||||
Notes [126] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [127] | ||||||||||||||||||||
P-value |
= 0.474 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-1.64
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-6.12 | ||||||||||||||||||||
upper limit |
2.85 | ||||||||||||||||||||
Notes [127] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|
|||||||||||||||||||||
End point title |
Average daily evening PEF | ||||||||||||||||||||
End point description |
E-peakflow meter/e-diary was completed at home on a daily basis morning and evening (daily download of the e-peakflow meter/e-diary). During the two wash-out periods, only the compliance to the wash-out medication was collected.
During the run-in period and the three treatment periods, PEF (L/min) was monitored twice daily before the intake of the run-in medication or study medication. Morning measurements were done approximately between 7:00 am and 9:00 am and evening measurements approximately between 7:00 pm and 9:00 pm. An alarm reminded the patients to perform measurements. During each measurement session, the patient performed three blows and data were recorded in the device.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Daily during run-in and treatment periods.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [128] - This is the actual number of patients on which the analysis was performed. [129] - This is the actual number of patients on which the analysis was performed. [130] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [131] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
11.94
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
7.41 | ||||||||||||||||||||
upper limit |
16.47 | ||||||||||||||||||||
Notes [131] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [132] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
14.22
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
9.72 | ||||||||||||||||||||
upper limit |
18.72 | ||||||||||||||||||||
Notes [132] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [133] | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
11.94
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
7.44 | ||||||||||||||||||||
upper limit |
16.44 | ||||||||||||||||||||
Notes [133] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [134] | ||||||||||||||||||||
P-value |
= 0.32 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
2.29
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.23 | ||||||||||||||||||||
upper limit |
6.8 | ||||||||||||||||||||
Notes [134] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [135] | ||||||||||||||||||||
P-value |
= 0.999 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-4.49 | ||||||||||||||||||||
upper limit |
4.5 | ||||||||||||||||||||
Notes [135] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [136] | ||||||||||||||||||||
P-value |
= 0.317 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-2.28
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-6.76 | ||||||||||||||||||||
upper limit |
2.2 | ||||||||||||||||||||
Notes [136] - This secondary efficacy variable was analysed on the ITT population using an ANOVA (analysis of variance) model including treatment, period and patient as fixed effects. |
|
|||||||||||||||||||||
End point title |
Change from baseline in pre-dose FVC on Day 14 | ||||||||||||||||||||
End point description |
Pre-dose FVC was recorded on Day 14 at 45 minutes and 10 minutes prior to study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [137] - This is the actual number of patients on which the analysis was performed. [138] - This is the actual number of patients on which the analysis was performed. [139] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [140] | ||||||||||||||||||||
P-value |
= 0.645 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.014
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.044 | ||||||||||||||||||||
upper limit |
0.072 | ||||||||||||||||||||
Notes [140] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [141] | ||||||||||||||||||||
P-value |
= 0.01 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.076
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.018 | ||||||||||||||||||||
upper limit |
0.133 | ||||||||||||||||||||
Notes [141] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [142] | ||||||||||||||||||||
P-value |
= 0.508 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.019
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.038 | ||||||||||||||||||||
upper limit |
0.077 | ||||||||||||||||||||
Notes [142] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [143] | ||||||||||||||||||||
P-value |
= 0.035 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.062
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.004 | ||||||||||||||||||||
upper limit |
0.12 | ||||||||||||||||||||
Notes [143] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [144] | ||||||||||||||||||||
P-value |
= 0.842 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.006
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.052 | ||||||||||||||||||||
upper limit |
0.063 | ||||||||||||||||||||
Notes [144] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=310 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
310
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [145] | ||||||||||||||||||||
P-value |
= 0.054 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.056
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.113 | ||||||||||||||||||||
upper limit |
0.001 | ||||||||||||||||||||
Notes [145] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in pre-dose FVC on Day 42 | ||||||||||||||||||||
End point description |
Pre-dose FVC was recorded on Day 42 at 45 minutes and 10 minutes prior to study drug intake.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [146] - This is the actual number of patients on which the analysis was performed. [147] - This is the actual number of patients on which the analysis was performed. [148] - This is the actual number of patients on which the analysis was performed. [149] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
TReatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [150] | ||||||||||||||||||||
P-value |
= 0.503 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.017
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.034 | ||||||||||||||||||||
upper limit |
0.068 | ||||||||||||||||||||
Notes [150] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and Baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [151] | ||||||||||||||||||||
P-value |
= 0.046 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.052
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.001 | ||||||||||||||||||||
upper limit |
0.102 | ||||||||||||||||||||
Notes [151] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [152] | ||||||||||||||||||||
P-value |
= 0.118 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.04
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.01 | ||||||||||||||||||||
upper limit |
0.091 | ||||||||||||||||||||
Notes [152] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [153] | ||||||||||||||||||||
P-value |
= 0.188 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.034
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.017 | ||||||||||||||||||||
upper limit |
0.085 | ||||||||||||||||||||
Notes [153] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305(subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [154] | ||||||||||||||||||||
P-value |
= 0.374 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.023
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.028 | ||||||||||||||||||||
upper limit |
0.074 | ||||||||||||||||||||
Notes [154] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [155] | ||||||||||||||||||||
P-value |
= 0.663 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.011
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.062 | ||||||||||||||||||||
upper limit |
0.039 | ||||||||||||||||||||
Notes [155] - This secondary efficacy variable was analysed on the ITT population using ANCOVA model including treatment, period and patient as fixed effects and baseline values as covariates. |
|
|||||||||||||||||||||
End point title |
Change from baseline in peak FVC on Day 1 | ||||||||||||||||||||
End point description |
The peak FVC is the maximum FVC value obtained between 15 minutes and 12 hours post-dose.
Post-dose FVC on Day 1 of each treatment period was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake.
Baseline is the average of the FVC pre-dose measurements on Day 1 of each period (recorded at 45 and 10 minuted prior to study drug intake).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [156] - This is the actual number of patients on which the analysis was performed. [157] - This is the actual number of patients on which the analysis was performed. [158] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [159] | ||||||||||||||||||||
P-value |
= 0.085 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.037
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.005 | ||||||||||||||||||||
upper limit |
0.079 | ||||||||||||||||||||
Notes [159] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [160] | ||||||||||||||||||||
P-value |
= 0.502 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.014
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.028 | ||||||||||||||||||||
upper limit |
0.056 | ||||||||||||||||||||
Notes [160] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [161] | ||||||||||||||||||||
P-value |
= 0.16 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.03
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.012 | ||||||||||||||||||||
upper limit |
0.072 | ||||||||||||||||||||
Notes [161] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [162] | ||||||||||||||||||||
P-value |
= 0.285 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.023
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.065 | ||||||||||||||||||||
upper limit |
0.019 | ||||||||||||||||||||
Notes [162] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [163] | ||||||||||||||||||||
P-value |
= 0.735 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.007
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.049 | ||||||||||||||||||||
upper limit |
0.035 | ||||||||||||||||||||
Notes [163] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [164] | ||||||||||||||||||||
P-value |
= 0.46 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.016
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.026 | ||||||||||||||||||||
upper limit |
0.057 | ||||||||||||||||||||
Notes [164] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|
|||||||||||||||||||||
End point title |
Change from baseline in peak FVC on Day 42 | ||||||||||||||||||||
End point description |
The peak FVC is the maximum FVC value obtained between 15 minutes and 12 hours post-dose.
Post-dose FVC on Day 1 of each treatment period was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake.
Baseline is the average of the FVC pre-dose measurements on Day 1 of each period (recorded at 45 and 10 minuted prior to study drug intake).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [165] - This is the actual number of patients on which the analysis was performed. [166] - This is the actual number of patients on which the analysis was performed. [167] - This is the actual number of patients on which the analysis was performed. [168] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [169] | ||||||||||||||||||||
P-value |
= 0.4 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.02
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.026 | ||||||||||||||||||||
upper limit |
0.066 | ||||||||||||||||||||
Notes [169] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [170] | ||||||||||||||||||||
P-value |
= 0.043 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.047
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.001 | ||||||||||||||||||||
upper limit |
0.092 | ||||||||||||||||||||
Notes [170] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [171] | ||||||||||||||||||||
P-value |
= 0.029 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.051
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.005 | ||||||||||||||||||||
upper limit |
0.097 | ||||||||||||||||||||
Notes [171] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=301 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [172] | ||||||||||||||||||||
P-value |
= 0.245 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.027
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.019 | ||||||||||||||||||||
upper limit |
0.073 | ||||||||||||||||||||
Notes [172] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [173] | ||||||||||||||||||||
P-value |
= 0.179 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.031
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.014 | ||||||||||||||||||||
upper limit |
0.077 | ||||||||||||||||||||
Notes [173] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an
innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [174] | ||||||||||||||||||||
P-value |
= 0.859 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.004
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.041 | ||||||||||||||||||||
upper limit |
0.05 | ||||||||||||||||||||
Notes [174] - The peak FVC was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline FVC (average of 45 and 10 minutes pre-dose FVC at Day 1) as covariate. |
|
|||||||||||||||||||||
End point title |
Change from baseline in FVC at each time point post-dose on Day 1 | ||||||||||||||||||||
End point description |
The baseline FVC is the mean of the pre-dose measurements recorded on Day 1 of each treatment period.
Post-dose FVC was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake on Day 1.
Only change from baseline at the last timepoint (12h post-dose) on Day 1 is reported in the system. For the data on the other timepoints on the same day see pdf attached.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: FVC Change D1.pdf) |
||||||||||||||||||||
Notes [175] - This is the actual number of patients on which the analysis was performed. [176] - This is the actual number of patients on which the analysis was performed. [177] - This is the actual number of patients on which the analysis was performed. [178] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from baseline in FVC at 2h post-dose on Day 14 | ||||||||||||||||||||
End point description |
The baseline FVC is the mean of the pre-dose measurements recorded on Day 1 of each treatment period.
Post-dose FVC was recorded at 2h on Day 14.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: FVC Change D14.pdf) |
||||||||||||||||||||
Notes [179] - This is the actual number of patients on which the analysis was performed. [180] - This is the actual number of patients on which the analysis was performed. [181] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from baseline in FVC at each time point post-dose on Day 42 | ||||||||||||||||||||
End point description |
The baseline FVC is the mean of the pre-dose measurements recorded on Day 1 of each treatment period.
Post-dose FVC was recorded at 15’; 30’; 45’; 1h; 2h; 3h, 4h,6h, 8h, 11h30 and 12h post-study drug intake on Day 42.
Only change from baseline at the last timepoint (12h post-dose) on Day 42 is reported in the system. For the data on the other timepoints on the same day, please see the pdf attached.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Attachments |
Untitled (Filename: FVC Change D42.pdf) |
||||||||||||||||||||
Notes [182] - This is the actual number of patients on which the analysis was performed. [183] - This is the actual number of patients on which the analysis was performed. [184] - This is the actual number of patients on which the analysis was performed. [185] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Average total daily asthma symptoms, night-time | ||||||||||||||||||||
End point description |
The average of daily asthma symptoms (morning/ evening) of a subgroup (Cough, Wheeze, Chest Tightness, Breathlessness) is the mean value of all morning/ evening measurements of that subgroup.
Results on the average total daily asthma symptoms score (night-time) during the treatment period are presented for the ITT population.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
At visit 1 (Screening Visit) and at the first and third visit of each tratment period.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [186] - This is the actual number of patients on which the analysis was performed. [187] - This is the actual number of patients on which the analysis was performed. [188] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [189] | ||||||||||||||||||||
P-value |
= 0.77 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.022
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.173 | ||||||||||||||||||||
upper limit |
0.128 | ||||||||||||||||||||
Notes [189] - This secondary efficacy variables were analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [190] | ||||||||||||||||||||
P-value |
= 0.682 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.031
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.181 | ||||||||||||||||||||
upper limit |
0.118 | ||||||||||||||||||||
Notes [190] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [191] | ||||||||||||||||||||
P-value |
= 0.85 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.014
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.164 | ||||||||||||||||||||
upper limit |
0.135 | ||||||||||||||||||||
Notes [191] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [192] | ||||||||||||||||||||
P-value |
= 0.909 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.009
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.158 | ||||||||||||||||||||
upper limit |
0.141 | ||||||||||||||||||||
Notes [192] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [193] | ||||||||||||||||||||
P-value |
= 0.915 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.008
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.141 | ||||||||||||||||||||
upper limit |
0.157 | ||||||||||||||||||||
Notes [193] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [194] | ||||||||||||||||||||
P-value |
= 0.825 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.017
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.132 | ||||||||||||||||||||
upper limit |
0.165 | ||||||||||||||||||||
Notes [194] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|
|||||||||||||||||||||
End point title |
Average total daily asthma symptoms, day-time | ||||||||||||||||||||
End point description |
The average of daily asthma symptoms (morning/ evening) of a subgroup (Cough, Wheeze, Chest Tightness, Breathlessness) is the mean value of all morning/ evening measurements of that subgroup.
Results on the average total daily asthma symptoms score (day-time) during the treatment period are presented for the ITT population.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
At visit 1 (Screening Visit) and at the first and third visit of each tratment period.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [195] - This is the actual number of patients on which the analysis was performed. [196] - This is the actual number of patients on which the analysis was performed. [197] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [198] | ||||||||||||||||||||
P-value |
= 0.917 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.008
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.165 | ||||||||||||||||||||
upper limit |
0.148 | ||||||||||||||||||||
Notes [198] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [199] | ||||||||||||||||||||
P-value |
= 0.792 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.021
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.134 | ||||||||||||||||||||
upper limit |
0.176 | ||||||||||||||||||||
Notes [199] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [200] | ||||||||||||||||||||
P-value |
= 0.656 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.035
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.12 | ||||||||||||||||||||
upper limit |
0.19 | ||||||||||||||||||||
Notes [200] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [201] | ||||||||||||||||||||
P-value |
= 0.713 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.029
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.127 | ||||||||||||||||||||
upper limit |
0.185 | ||||||||||||||||||||
Notes [201] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [202] | ||||||||||||||||||||
P-value |
= 0.582 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.043
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.112 | ||||||||||||||||||||
upper limit |
0.199 | ||||||||||||||||||||
Notes [202] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [203] | ||||||||||||||||||||
P-value |
= 0.855 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.014
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.14 | ||||||||||||||||||||
upper limit |
0.169 | ||||||||||||||||||||
Notes [203] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|
|||||||||||||||||||||
End point title |
Percentage of asthma control days | ||||||||||||||||||||
End point description |
The percentage is calculated as the number of asthma control days / number of days with available data.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Measured between the first and the third visit of each treatment period.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [204] - This is the actual number of patients on which the analysis was performed. [205] - This is the actual number of patients on which the analysis was performed. [206] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [207] | ||||||||||||||||||||
P-value |
= 0.481 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
1.3
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.3 | ||||||||||||||||||||
upper limit |
4.8 | ||||||||||||||||||||
Notes [207] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [208] | ||||||||||||||||||||
P-value |
= 0.484 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
1.3
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.3 | ||||||||||||||||||||
upper limit |
4.8 | ||||||||||||||||||||
Notes [208] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [209] | ||||||||||||||||||||
P-value |
= 0.562 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
1
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.5 | ||||||||||||||||||||
upper limit |
4.6 | ||||||||||||||||||||
Notes [209] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [210] | ||||||||||||||||||||
P-value |
= 0.99 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-3.6 | ||||||||||||||||||||
upper limit |
3.5 | ||||||||||||||||||||
Notes [210] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [211] | ||||||||||||||||||||
P-value |
= 0.896 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.2
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-3.8 | ||||||||||||||||||||
upper limit |
3.3 | ||||||||||||||||||||
Notes [211] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [212] | ||||||||||||||||||||
P-value |
= 0.906 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.2
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-3.7 | ||||||||||||||||||||
upper limit |
3.3 | ||||||||||||||||||||
Notes [212] - This secondary efficacy variable was analysed on the ITT population using an analysis of variance (ANOVA) model including treatment, period and patient as fixed effects. |
|
|||||||||||||||||||||
End point title |
Average use of rescue medication (number of puffs/day) | ||||||||||||||||||||
End point description |
The average use of rescue medication (number of puffs per day) is determined as the total number of puffs of rescue mediation taken / number of days with available data.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Daily during run-in/wash-out & treatment periods.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [213] - This is the actual number of patients on which the analysis was performed. [214] - This is the actual number of patients on which the analysis was performed. [215] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [216] | ||||||||||||||||||||
P-value |
= 0.55 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.2 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [216] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [217] | ||||||||||||||||||||
P-value |
= 0.883 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [217] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [218] | ||||||||||||||||||||
P-value |
= 0.325 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.1
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.2 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [218] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [219] | ||||||||||||||||||||
P-value |
= 0.649 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [219] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [220] | ||||||||||||||||||||
P-value |
= 0.701 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [220] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [221] | ||||||||||||||||||||
P-value |
= 0.4 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.2 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [221] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|
|||||||||||||||||||||
End point title |
Average use of rescue medication (number of times/day) | ||||||||||||||||||||
End point description |
The average use of rescue medication (number of times per day) is determined as the total number of times of rescue medication taken/ number of days with available data.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Daily during run-in/wash-out & treatment periods.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [222] - This is the actual number of patients on which the analysis was performed. [223] - This is the actual number of patients on which the analysis was performed. [224] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=304 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [225] | ||||||||||||||||||||
P-value |
= 0.95 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [225] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [226] | ||||||||||||||||||||
P-value |
= 0.744 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [226] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [227] | ||||||||||||||||||||
P-value |
= 0.629 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [227] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=306 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [228] | ||||||||||||||||||||
P-value |
= 0.793 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [228] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [229] | ||||||||||||||||||||
P-value |
= 0.674 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [229] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=309 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
309
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [230] | ||||||||||||||||||||
P-value |
= 0.875 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
adjusted mean difference | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||
upper limit |
0.1 | ||||||||||||||||||||
Notes [230] - The average use of rescue medication was analysed by means of an ANOVA model with treatment, patient and period as fixed effects, without multiplicity adjustments. |
|
|||||||||||||||||||||
End point title |
Change from baseline in ACQ total score on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the calculated Asthma Control Questionnaire (ACQ) score of Day 1 of the respective treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [231] - This is the actual number of patients on which the analysis was performed. [232] - This is the actual number of patients on which the analysis was performed. [233] - This is the actual number of patients on which the analysis was performed. [234] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
Statistical analysis title |
Treatment A vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=302 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment D - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
302
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [235] | ||||||||||||||||||||
P-value |
= 0.835 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.011
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.116 | ||||||||||||||||||||
upper limit |
0.093 | ||||||||||||||||||||
Notes [235] - The change from baseline in ACQ total score on Day 42 was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline ACQ total score as covariate. No multiplicity adjustments are done. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [236] | ||||||||||||||||||||
P-value |
= 0.583 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.029
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.132 | ||||||||||||||||||||
upper limit |
0.074 | ||||||||||||||||||||
Notes [236] - The change from baseline in ACQ total score on Day 42 was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline ACQ total score as covariate. No multiplicity adjustments are done. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment D | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=307 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment D - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
307
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [237] | ||||||||||||||||||||
P-value |
= 0.727 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.018
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.122 | ||||||||||||||||||||
upper limit |
0.085 | ||||||||||||||||||||
Notes [237] - The change from baseline in ACQ total score on Day 42 was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline ACQ total score as covariate. No multiplicity adjustments are done. |
|||||||||||||||||||||
Statistical analysis title |
Treatment B vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=303 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment B - ITT population v Treatment A - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
303
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [238] | ||||||||||||||||||||
P-value |
= 0.737 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.018
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.122 | ||||||||||||||||||||
upper limit |
0.086 | ||||||||||||||||||||
Notes [238] - The change from baseline in ACQ total score on Day 42 was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline ACQ total score as covariate. No multiplicity adjustments are done. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment A | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=305 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment A - ITT population v Treatment C - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [239] | ||||||||||||||||||||
P-value |
= 0.89 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
-0.007
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.111 | ||||||||||||||||||||
upper limit |
0.086 | ||||||||||||||||||||
Notes [239] - The change from baseline in ACQ total score on Day 42 was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline ACQ total score as covariate. No multiplicity adjustments are done. |
|||||||||||||||||||||
Statistical analysis title |
Treatment C vs Treatment B | ||||||||||||||||||||
Statistical analysis description |
In a cross-over study, groups examined should not be added. The number N=308 (subject analysis set) is an innate error of the EudraCT database system.
|
||||||||||||||||||||
Comparison groups |
Treatment C - ITT population v Treatment B - ITT population
|
||||||||||||||||||||
Number of subjects included in analysis |
308
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [240] | ||||||||||||||||||||
P-value |
= 0.841 | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||||||||||
Point estimate |
0.011
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.093 | ||||||||||||||||||||
upper limit |
0.114 | ||||||||||||||||||||
Notes [240] - The change from baseline in ACQ total score on Day 42 was analysed by means of an ANCOVA model with treatment, patient and period as fixed effects and baseline ACQ total score as covariate. No multiplicity adjustments are done. |
|
|||||||||||||||||||||
End point title |
SBP change from baseline on Day 14 | ||||||||||||||||||||
End point description |
Baseline is the pre-dose measurement on Day 1 in each treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [241] - This is the actual number of patients on which the analysis was performed. [242] - This is the actual number of patients on which the analysis was performed. [243] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
HR change from baseline post-dose on Day 1 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [244] - This is the actual number of patients on which the analysis was performed. [245] - This is the actual number of patients on which the analysis was performed. [246] - This is the actual number of patients on which the analysis was performed. [247] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
PR change from baseline post-dose on Day 1 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [248] - This is the actual number of patients on which the analysis was performed. [249] - This is the actual number of patients on which the analysis was performed. [250] - This is the actual number of patients on which the analysis was performed. [251] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
QRS change from baseline post-dose on Day 1 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [252] - This is the actual number of patients on which the analysis was performed. [253] - This is the actual number of patients on which the analysis was performed. [254] - This is the actual number of patients on which the analysis was performed. [255] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
QTcF change from baseline post-dose on Day 1 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 1
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [256] - This is the actual number of patients on which the analysis was performed. [257] - This is the actual number of patients on which the analysis was performed. [258] - This is the actual number of patients on which the analysis was performed. [259] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
SBP change from baseline on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the pre-dose measurement on Day 1 in each treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [260] - This is the actual number of patients on which the analysis was performed. [261] - This is the actual number of patients on which the analysis was performed. [262] - This is the actual number of patients on which the analysis was performed. [263] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
DBP change from baseline on Day 14 | ||||||||||||||||||||
End point description |
Baseline is the pre-dose measurement on Day 1 in each treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 14
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [264] - This is the actual number of patients on which the analysis was performed. [265] - This is the actual number of patients on which the analysis was performed. [266] - This is the actual number of patients on which the analysis was performed. [267] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
DBP change from baseline on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the pre-dose measurement on Day 1 in each treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [268] - This is the actual number of patients on which the analysis was performed. [269] - This is the actual number of patients on which the analysis was performed. [270] - This is the actual number of patients on which the analysis was performed. [271] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
QTcF change from baseline pre-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [272] - This is the actual number of patients on which the analysis was performed. [273] - This is the actual number of patients on which the analysis was performed. [274] - This is the actual number of patients on which the analysis was performed. [275] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
QTcF change from baseline post-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [276] - This is the actual number of patients on which the analysis was performed. [277] - This is the actual number of patients on which the analysis was performed. [278] - This is the actual number of patients on which the analysis was performed. [279] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
HR change from baseline pre-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [280] - This is the actual number of patients on which the analysis was performed. [281] - This is the actual number of patients on which the analysis was performed. [282] - This is the actual number of patients on which the analysis was performed. [283] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
HR change from baseline post-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day1 in each treatment period. Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [284] - This is the actual number of patients on which the analysis was performed. [285] - This is the actual number of patients on which the analysis was performed. [286] - This is the actual number of patients on which the analysis was performed. [287] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
PR change from baseline pre-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period. Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [288] - This is the actual number of patients on which the analysis was performed. [289] - This is the actual number of patients on which the analysis was performed. [290] - This is the actual number of patients on which the analysis was performed. [291] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
PR change from baseline post-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [292] - This is the actual number of patients on which the analysis was performed. [293] - This is the actual number of patients on which the analysis was performed. [294] - This is the actual number of patients on which the analysis was performed. [295] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
QRS change from baseline pre-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [296] - This is the actual number of patients on which the analysis was performed. [297] - This is the actual number of patients on which the analysis was performed. [298] - This is the actual number of patients on which the analysis was performed. [299] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
QRS change from baseline post-dose on Day 42 | ||||||||||||||||||||
End point description |
Baseline is the average of the 3 individual pre-dose values on Day 1 in each treatment period.
Patients with a pacemaker are excluded from this summary. ECGs at a timepoint with Atrial Fibrillation, Atrial Flutter or Ectopic Supraventricular Rhythm are also excluded.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
On Day 42
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [300] - This is the actual number of patients on which the analysis was performed. [301] - This is the actual number of patients on which the analysis was performed. [302] - This is the actual number of patients on which the analysis was performed. [303] - This is the actual number of patients on which the analysis was performed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
At each visit from Visit 1 (Screening) to Visit 10 and, afterwards, to follow-up.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Treatment A - safety population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment B - safety population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment C - safety population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment D - safety population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
There are no limitations or caveats to this summary of results. |