Clinical Trial Results:
A RANDOMISED, DOUBLE-BLIND, PLACEBO CONTROLLED, REPEATED DOSE, THREE-WAY CROSSOVER STUDY TO EVALUATE THE PHARMACODYNAMICS, PHARMACOKINETICS AND SAFETY OF TWO DOSES OF CHF 6001 DPI IN SUBJECTS WITH MODERATE, SEVERE COPD.
Summary
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EudraCT number |
2015-005550-35 |
Trial protocol |
GB DE |
Global end of trial date |
28 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jan 2019
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First version publication date |
06 Jan 2019
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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-06001AA1-10
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03004417 | ||
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., Chiesi Farmaceutici S.p.A., +39 0521 2791, clinicaltrials_info@chiesi.com
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Scientific contact |
Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., Chiesi Farmaceutici S.p.A., +39 0521 2791, clinicaltrials_info@chiesi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
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 |
19 Nov 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Dec 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Dec 2017
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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 |
The objectives of the study were:
- To evaluate the effect of CHF 6001 on biomarkers of inflammation in induced sputum and in blood, on pulmonary function and on symptoms benefits in comparison with placebo;
- To evaluate the safety and tolerability of CHF 6001;
- To assess the PK profile of CHF 6001 and its metabolites at steady state in patients with moderate, severe COPD.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, with the Good Clinical Practice (GCP) guidelines in force during study conduct and following all other requirements of local laws.
At all visits from screening onwards, concomitant medications and adverse events (AEs) were recorded. Height and weight were measured at screening and weight was measured at Day 1 and Day 32 of each treatment period. Physical examinations were performed at screening, on Day 1 and Day 32 of each treatment period and at the follow-up visit. Additional physical examinations could have been performed on Day 20 and Day 26 of each treatment period, as needed. Vital signs and 12-lead electrocardiograms (ECGs) were recorded at screening and pre-dose on Day 1 and Day 32 of each treatment period.
Patients were provided with salbutamol as rescue medication to use as needed throughout the study.
Patients were maintained on their regular medication (triple therapy) throughout the study.
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Background therapy |
Patient's receiving daily maintenance with triple therapy (i.e. inhaled corticosteroid [ICS] plus long-acting beta-2 agonist [LABA] plus long-acting muscarinic anticholinergenic [LAMA]) at a stable dose and dosing regimen for at least 2 months prior to screening were enrolled in the study. Patients continued to receive this triple background medication throughout the study. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Oct 2016
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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 |
United Kingdom: 21
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Country: Number of subjects enrolled |
Germany: 40
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Worldwide total number of subjects |
61
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EEA total number of subjects |
61
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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) |
24
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From 65 to 84 years |
37
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85 years and over |
0
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Recruitment
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Recruitment details |
140 patients were screened according to inclusion/exclusion criteria; 61 patients were randomised to 1 of 6 treatment sequences (Sequence CHF 6001 1600 µg [L]-CHF 6001 3200 µg [H]-placebo [P] [n=11], Sequence L-P-H [n=10], Sequence H-L-P [n=10], Sequence H-P-L [n=12], Sequence P-L-H [n=9], Sequence P-H-L [n=9]); 54 patients completed the study. | ||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The study comprised a pre-screening visit, occurring no more than 1 week prior to a screening visit. At the screening visit, inclusion/exclusion criteria were assessed. There were 79 screening failures (78 patients did not meet inclusion/exclusion criteria and 1 patient was lost to follow-up). | ||||||||||||||||||||||||||||||||||||||||||
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 |
Investigator, Monitor, Data analyst, Carer, Assessor, Subject | ||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
At randomisation, patients were sequentially assigned to one of the six treatment sequences using a balanced block randomisation scheme and a pre-established randomisation list.
The randomisation list was provided to the labelling facility and to the analytical and biomarker laboratories, but was not available to patients, investigators, monitors or employees of the centre involved in the management of the study before unblinding of the data, unless in case of emergency.
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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 L-H-P | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 6001
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Investigational medicinal product code |
CHF 6001
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Arm title
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Sequence L-P-H | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 6001
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Investigational medicinal product code |
CHF 6001
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Arm title
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Sequence H-L-P | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 6001
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Investigational medicinal product code |
CHF 6001
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Arm title
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Sequence H-P-L | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 6001
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Investigational medicinal product code |
CHF 6001
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Arm title
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Sequence P-L-H | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 6001
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Investigational medicinal product code |
CHF 6001
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Arm title
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Sequence P-H-L | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 6001
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Investigational medicinal product code |
CHF 6001
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Study medication was administered using NEXThaler® technology (Dry Powder Inhaler, DPI). The study treatment kit for each period contained four inhalers (two inhalers for the morning administration and two inhalers for the evening administration). During each 32 (+2) day treatment period, the study medication was administered twice daily with patients taking two puffs from each "morning" inhaler and two puffs from each "evening" inhaler, adding up to eight puffs per day. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = placebo.
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Baseline characteristics reporting groups
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Reporting group title |
Sequence L-H-P
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Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence L-P-H
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence H-L-P
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence H-P-L
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence P-L-H
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence P-H-L
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Sequence L-H-P
|
||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||
Reporting group title |
Sequence L-P-H
|
||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||
Reporting group title |
Sequence H-L-P
|
||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||
Reporting group title |
Sequence H-P-L
|
||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||
Reporting group title |
Sequence P-L-H
|
||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||
Reporting group title |
Sequence P-H-L
|
||
Reporting group description |
Patients were randomised to receive three different treatments (total daily doses of 1600 µg and 3200 µg of CHF 6001 DPI or matched placebo given twice daily) during three treatment periods. Treatment periods lasted 32 (+2) days and were separated by two washout periods of 28 to 42 days. Treatment L = CHF 6001 1600 µg; Treatment H = CHF 6001 3200 µg; Treatment P = matched placebo. | ||
Subject analysis set title |
L: CHF 6001 1600 µg - PD
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Treatment L: CHF 6001 1600 µg; the population was defined as all patients from the Safety population with available evaluation in at least two treatment periods excluding patients without any pharmacodynamic (PD) measurement and with major protocol deviations affecting the PD evaluations.
|
||
Subject analysis set title |
H: CHF 6001 3200 µg - PD
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Treatment H: CHF 6001 1600 µg; the population was defined as all patients from the Safety population with available evaluation in at least two treatment periods excluding patients without any pharmacodynamic (PD) measurement and with major protocol deviations affecting the PD evaluations.
|
||
Subject analysis set title |
P: Placebo - PD
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Treatment P : placebo; the population was defined as all patients from the Safety population with available evaluation in at least two treatment periods excluding patients without any pharmacodynamic (PD) measurement and with major protocol deviations affecting the PD evaluations.
|
||
Subject analysis set title |
L: CHF 6001 1600 µg - PK
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PK population consisted of all patients from the Safety population excluding patients without any valid PK assessment and with major protocol deviations affecting the PK evaluations.
|
||
Subject analysis set title |
H: CHF 6001 3200 µg - PK
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PK population consisted of all patients from the Safety population excluding patients without any valid PK assessment and with major protocol deviations affecting the PK evaluations.
|
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in TNF-α in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
TNF-α level in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
86
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [1] | ||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.482
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.314 | ||||||||||||||||
upper limit |
0.741 | ||||||||||||||||
Notes [1] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
TNF-α level in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
H: CHF 6001 3200 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [2] | ||||||||||||||||
P-value |
= 0.049 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.651
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.424 | ||||||||||||||||
upper limit |
0.998 | ||||||||||||||||
Notes [2] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end to treatment (mean Day 20, 26 and 32 values) in absolute neutrophil count in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute neutrophil count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v L: CHF 6001 1600 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [3] | ||||||||||||||||
P-value |
= 0.183 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.201
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.916 | ||||||||||||||||
upper limit |
1.575 | ||||||||||||||||
Notes [3] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute neutrophil count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [4] | ||||||||||||||||
P-value |
= 0.807 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.034
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.789 | ||||||||||||||||
upper limit |
1.354 | ||||||||||||||||
Notes [4] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in absolute eosinophil count in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean of Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute eosinophil count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [5] | ||||||||||||||||
P-value |
= 0.371 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.817
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.522 | ||||||||||||||||
upper limit |
1.277 | ||||||||||||||||
Notes [5] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute eosinophil count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [6] | ||||||||||||||||
P-value |
= 0.508 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.862
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.552 | ||||||||||||||||
upper limit |
1.345 | ||||||||||||||||
Notes [6] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in absolute macrophage count in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute macrophage count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [7] | ||||||||||||||||
P-value |
= 0.04 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.756
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.579 | ||||||||||||||||
upper limit |
0.987 | ||||||||||||||||
Notes [7] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute macrophage count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [8] | ||||||||||||||||
P-value |
= 0.228 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.851
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.653 | ||||||||||||||||
upper limit |
1.108 | ||||||||||||||||
Notes [8] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in absolute lymphocyte count in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute lymphocyte count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data was log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [9] | ||||||||||||||||
P-value |
= 0.289 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.68
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.331 | ||||||||||||||||
upper limit |
1.395 | ||||||||||||||||
Notes [9] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Absolute lymphocyte count in induced sputum, obtained on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [10] | ||||||||||||||||
P-value |
= 0.357 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.716
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.349 | ||||||||||||||||
upper limit |
1.466 | ||||||||||||||||
Notes [10] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in percentage of neutrophils in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of neutrophils in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [11] | ||||||||||||||||
P-value |
= 0.023 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.059
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.008 | ||||||||||||||||
upper limit |
1.112 | ||||||||||||||||
Notes [11] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of neutrophils in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [12] | ||||||||||||||||
P-value |
= 0.087 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.044
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.994 | ||||||||||||||||
upper limit |
1.097 | ||||||||||||||||
Notes [12] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in percentage of eosinophils in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean of Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of eosinophils in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [13] | ||||||||||||||||
P-value |
= 0.103 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.754
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.536 | ||||||||||||||||
upper limit |
1.06 | ||||||||||||||||
Notes [13] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of eosinophils in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [14] | ||||||||||||||||
P-value |
= 0.53 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.898
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.64 | ||||||||||||||||
upper limit |
1.26 | ||||||||||||||||
Notes [14] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in percentage of macrophages in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of macrophages in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [15] | ||||||||||||||||
P-value |
= 0.009 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.708
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.547 | ||||||||||||||||
upper limit |
0.916 | ||||||||||||||||
Notes [15] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of macrophages in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [16] | ||||||||||||||||
P-value |
= 0.27 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.867
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.671 | ||||||||||||||||
upper limit |
1.12 | ||||||||||||||||
Notes [16] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in percentage of lymphocytes in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean of Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of lymphocytes in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [17] | ||||||||||||||||
P-value |
= 0.279 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.85
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.632 | ||||||||||||||||
upper limit |
1.143 | ||||||||||||||||
Notes [17] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
percentage of lymphocytes in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [18] | ||||||||||||||||
P-value |
= 0.221 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.832
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.619 | ||||||||||||||||
upper limit |
1.119 | ||||||||||||||||
Notes [18] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in IL-6 in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
IL-6 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
102
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [19] | ||||||||||||||||
P-value |
= 0.895 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.013
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.83 | ||||||||||||||||
upper limit |
1.236 | ||||||||||||||||
Notes [19] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
IL-6 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [20] | ||||||||||||||||
P-value |
= 0.002 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.351
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.116 | ||||||||||||||||
upper limit |
1.636 | ||||||||||||||||
Notes [20] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in IL-8 in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily included the change from baseline in TNF-α in induced sputum as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
IL-8 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [21] | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.67
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.54 | ||||||||||||||||
upper limit |
0.83 | ||||||||||||||||
Notes [21] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
IL-8 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
108
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [22] | ||||||||||||||||
P-value |
= 0.035 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.8
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.64 | ||||||||||||||||
upper limit |
0.98 | ||||||||||||||||
Notes [22] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in MIP1β in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
MIP1β in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
65
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [23] | ||||||||||||||||
P-value |
= 0.002 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.627
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.471 | ||||||||||||||||
upper limit |
0.834 | ||||||||||||||||
Notes [23] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
MIP1β in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
72
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [24] | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.625
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.478 | ||||||||||||||||
upper limit |
0.818 | ||||||||||||||||
Notes [24] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in MCP-1 in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
MCP-1 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data werelog-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
96
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [25] | ||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.715
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.588 | ||||||||||||||||
upper limit |
0.87 | ||||||||||||||||
Notes [25] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
MCP-1 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
101
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [26] | ||||||||||||||||
P-value |
= 0.105 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.852
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.702 | ||||||||||||||||
upper limit |
1.035 | ||||||||||||||||
Notes [26] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in leukotriene B4 in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Leukotriene B4 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
103
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [27] | ||||||||||||||||
P-value |
= 0.015 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.659
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.472 | ||||||||||||||||
upper limit |
0.919 | ||||||||||||||||
Notes [27] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Leukotriene B4 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [28] | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.561
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.405 | ||||||||||||||||
upper limit |
0.777 | ||||||||||||||||
Notes [28] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (mean Day 20, 26 and 32 values) in MMP9 in induced sputum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (mean Day 20, 26 and 32 values)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
MMP9 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [29] | ||||||||||||||||
P-value |
= 0.043 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.766
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.592 | ||||||||||||||||
upper limit |
0.992 | ||||||||||||||||
Notes [29] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
MMP9 in induced sputum on Days 20, 26 and 32 was averaged for each subject when receiving each treatment. The averaged values were used in the analysis. Mean change from baseline was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [30] | ||||||||||||||||
P-value |
= 0.038 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.759
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.585 | ||||||||||||||||
upper limit |
0.985 | ||||||||||||||||
Notes [30] - Explorative |
|
|||||||||||||
End point title |
PK sputum concentration for CHF 6001 at steady state | ||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured on Day 20, Day 26 or Day 32 at 2 hours post-dose.
Note: an aliquot of one of the sputum collections performed on Day 20, 26 or 32 was used for CHF 6001 determination.
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (Day 32) in IL-6 in serum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily included the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (Day 32)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
90
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [31] | ||||||||||||||||
P-value |
= 0.323 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.127
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.887 | ||||||||||||||||
upper limit |
1.432 | ||||||||||||||||
Notes [31] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
92
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [32] | ||||||||||||||||
P-value |
= 0.224 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.158
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.912 | ||||||||||||||||
upper limit |
1.47 | ||||||||||||||||
Notes [32] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (Day 32) in IL-8 in serum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (Day 32)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Non-normally distributed data was log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.726 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.022
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.906 | ||||||||||||||||
upper limit |
1.152 | ||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Non-normally distributed data was log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
105
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.721 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.979
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.868 | ||||||||||||||||
upper limit |
1.103 |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (Day 32) in TNF-α in vivo in serum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (Day 32)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
108
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [33] | ||||||||||||||||
P-value |
= 0.344 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.052
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.946 | ||||||||||||||||
upper limit |
1.171 | ||||||||||||||||
Notes [33] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
108
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [34] | ||||||||||||||||
P-value |
= 0.354 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
1.052
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.944 | ||||||||||||||||
upper limit |
1.173 | ||||||||||||||||
Notes [34] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (Day 32) in TNF-α ex vivo stimulated in plasma | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (Day 32)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
L: CHF 6001 1600 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
111
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [35] | ||||||||||||||||
P-value |
= 0.057 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.661
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.431 | ||||||||||||||||
upper limit |
1.013 | ||||||||||||||||
Notes [35] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
H: CHF 6001 3200 µg - PD v P: Placebo - PD
|
||||||||||||||||
Number of subjects included in analysis |
112
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [36] | ||||||||||||||||
P-value |
= 0.006 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.548
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.357 | ||||||||||||||||
upper limit |
0.841 | ||||||||||||||||
Notes [36] - Explorative |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (Day 32) in SP-D in serum | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to end of treatment (Day 32)
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
CHF 6001 1600 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v L: CHF 6001 1600 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [37] | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.8
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.74 | ||||||||||||||||
upper limit |
0.87 | ||||||||||||||||
Notes [37] - Explorative |
|||||||||||||||||
Statistical analysis title |
CHF 6001 3200 µg vs. placebo | ||||||||||||||||
Statistical analysis description |
Mean change from baseline to Day 32 was compared between treatments using an analysis of covariance (ANCOVA), including treatment, subject and period as fixed effects and baseline values as covariate. Data were log-transformed before analysis and results presented as ratio of geometric means.
|
||||||||||||||||
Comparison groups |
P: Placebo - PD v H: CHF 6001 3200 µg - PD
|
||||||||||||||||
Number of subjects included in analysis |
108
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [38] | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
ratio of geometric means | ||||||||||||||||
Point estimate |
0.83
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.77 | ||||||||||||||||
upper limit |
0.9 | ||||||||||||||||
Notes [38] - Explorative |
|
|||||||||||||
End point title |
Area under the plasma concentration-time curve for CHF 6001 from 0 to 12 hours post-dose at steady-state | ||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured at Day 32 (steady-state).
Blood samples were collected on Day 32 of each treatment period at 10 timepoints (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post-dose).
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Maximum plasma concentration of CHF 6001 at steady-state | ||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured on Day 32 (steady-state).
Blood samples were collected on Day 32 of each treatment period at 10 timepoints (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post-dose).
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from baseline to end of treatment (pre-dose Day 32) in FEV1 | ||||||||||||||||
End point description |
Note: all endpoints in this study were considered exploratory and none were defined as primary, secondary etc. In order to present results in the EudraCT system we have arbitrarily considered the change from baseline in TNF-α in induced sputum as the relevant endpoint to be labelled as the primary endpoint. All other endpoints were arbitrarily assigned as secondary endpoints.
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End point type |
Secondary
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End point timeframe |
Baseline to end of treatment (pre-dose Day 32)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
The reporting period for AEs was from the signature of the informed consent form until the patient's participation in the study ended.
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Adverse event reporting additional description |
All AEs starting on or after the time of first randomised study drug were classified as treatment-emergent adverse events (TEAEs) and were analysed in this study.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
L: CHF 6001 1600 µg
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Reporting group description |
Treatment L = CHF 6001 1600 µg. The safety population was defined as all randomised patients who received at least one dose of the study medication. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
H: CHF 6001 3200 µg
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Reporting group description |
Treatment H = CHF 6001 3200 µg. The safety population was defined as all randomised patients who received at least one dose of the study medication. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
P: Placebo
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Reporting group description |
Treatment P = placebo. The safety population was defined as all randomised patients who received at least one dose of the study medication. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Aug 2016 |
Protocol v 2.0. was issued on 25 August 2016 to implement comments raised by the authority MHRA to monitor specifically psychiatric adverse events. It was submitted to both MHRA and EC on the 26th of August 2016 and approved by both on the 09th of September 2016. It was also submitted to both BfArM and EC on the 19th and the 21st of September 2016 respectively, and approved by BfArM on the 5th of October and by the EC on the 01st of December 2016. |
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29 Sep 2016 |
Protocol v 3.0 was issued on 29 Sep 2016 to implement a smoking diary to monitor the change in the patients smoking habits. It was submitted to both EC and BfArM on the 26 and 27 October 2016 respectively and approved by the EC the 1st December 2016 alongside the approval of the version 2.0 of the protocol, while BfArM considered it as non-substantial amendment. It was also submitted to both MHRA and EC on the 21st of October 2016 and approved by both, the 25th of November 2016. |
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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. | |||
None reported |