Clinical Trial Results:
A Single-Dose, Open-Label, Randomized, 3-way Crossover, Clinical Pharmacology Study of CHF 1535 100/6 pMDI (fixed combination of Beclomethasone Dipropionate 100 μg plus Formoterol Fumarate 6 μg) with or without Spacer Device versus the free Combination of Licensed Beclomethasone pMDI and Formoterol pMDI in Asthmatic Adolescent Patients and One Open-Arm for Adult Patients as Control Group treated with CHF 1535 100/6 pMDI.
Summary
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EudraCT number |
2011-005108-14 |
Trial protocol |
PL |
Global end of trial date |
24 Aug 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Nov 2017
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First version publication date |
10 Nov 2017
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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-1104-PR-0062
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01803087 | ||
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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000548-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Mar 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Aug 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Aug 2012
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate, in adolescents, the systemic exposure to B17MP (active metabolite of BDP) as AUC0-t, after inhalation of CHF 1535 100/6 pMDI with and without spacer device (AeroChamber Plus™) in comparison with the already licensed free combination of BDP pMDI and Formoterol pMDI without spacer.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines and local law requirements. Other than routine care, no specific measures for protection of trial subjects were implemented.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Feb 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 60
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Worldwide total number of subjects |
60
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EEA total number of subjects |
60
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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) |
30
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Adults (18-64 years) |
30
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from subjects attending the outpatient’s hospital clinics or independent Clinical Research Organisation. Subjects were selected and randomised according to the inclusion criteria. | |||||||||||||||||||||||||
Pre-assignment
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Screening details |
In total, 30 adolescents and 30 adults were screened. No subjects failed screening; all 30 adolescents were randomised to one of 3 treatment sequences (TEST 1/REF/TEST 2, TEST 2/TEST 1/REF, REF/TEST 2/TEST 1), i.e., 10 subjects per treatment sequence, and received study drugs, and all 30 adults received a single dose of control drug (CTR) | |||||||||||||||||||||||||
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 |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||||||
Blinding implementation details |
As this is an open-label study, blinding is not applicable.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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TEST 1/REF/TEST 2 | |||||||||||||||||||||||||
Arm description |
Adolescent subjects took the following single-day treatments in sequence: • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
CHF 1535 100/6 pMDI, 4 puffs (total dose of BDP 400 μg / FF 24 μg) CHF 1535 100/6 pMDI, without (TEST 1) or with (TEST 2) AeroChamber Plus™
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Investigational medicinal product name |
beclomethasone dipropionate + formoterol fumarate
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Investigational medicinal product code |
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Other name |
BDP, FF
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)
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Arm title
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TEST 2/TEST 1/REF | |||||||||||||||||||||||||
Arm description |
Adolescent subjects took the following single-day treatments in sequence: • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
CHF 1535 100/6 pMDI, 4 puffs (total dose of BDP 400 μg / FF 24 μg) CHF 1535 100/6 pMDI, without (TEST 1) or with (TEST 2) AeroChamber Plus™
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Investigational medicinal product name |
beclomethasone dipropionate + formoterol fumarate
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Investigational medicinal product code |
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Other name |
BDP, FF
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)
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Arm title
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REF/TEST 2/TEST 1 | |||||||||||||||||||||||||
Arm description |
Adolescent subjects took the following single-day treatments in sequence: • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535
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Investigational medicinal product code |
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Other name |
beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
CHF 1535 100/6 pMDI, 4 puffs (total dose of BDP 400 μg / FF 24 μg) CHF 1535 100/6 pMDI, without (TEST 1) or with (TEST 2) AeroChamber Plus™
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Investigational medicinal product name |
beclomethasone dipropionate + formoterol fumarate
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Investigational medicinal product code |
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Other name |
BDP, FF
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)
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Arm title
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CONTROL | |||||||||||||||||||||||||
Arm description |
Adult patients (N=30) receiving a single dose of control drug (CTR) = 4 puffs of fixed combination CHF 1535 100/6 pMDI, for a total dose of BDP 400 μg / FF 24 μg). Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | |||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||
Investigational medicinal product name |
Foster
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Investigational medicinal product code |
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Other name |
CHF 1535 100/6 pMDI, beclomethasone / formoterol fixed combination
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
In one single-day treatment visit, subjects (all adults) were to take 4 puffs of fixed combination CHF 1535 100/6 pMDI (CONTROL
treatment – CTR) for a total dose of BDP 400 μg / FF 24 μg.
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Baseline characteristics reporting groups
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Reporting group title |
TEST 1/REF/TEST 2
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Reporting group description |
Adolescent subjects took the following single-day treatments in sequence: • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TEST 2/TEST 1/REF
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Reporting group description |
Adolescent subjects took the following single-day treatments in sequence: • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
REF/TEST 2/TEST 1
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Reporting group description |
Adolescent subjects took the following single-day treatments in sequence: • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CONTROL
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Reporting group description |
Adult patients (N=30) receiving a single dose of control drug (CTR) = 4 puffs of fixed combination CHF 1535 100/6 pMDI, for a total dose of BDP 400 μg / FF 24 μg). Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
TEST 1/REF/TEST 2
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Reporting group description |
Adolescent subjects took the following single-day treatments in sequence: • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||
Reporting group title |
TEST 2/TEST 1/REF
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Reporting group description |
Adolescent subjects took the following single-day treatments in sequence: • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||
Reporting group title |
REF/TEST 2/TEST 1
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Reporting group description |
Adolescent subjects took the following single-day treatments in sequence: • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||
Reporting group title |
CONTROL
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Reporting group description |
Adult patients (N=30) receiving a single dose of control drug (CTR) = 4 puffs of fixed combination CHF 1535 100/6 pMDI, for a total dose of BDP 400 μg / FF 24 μg). Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2. | ||
Subject analysis set title |
TEST 1 - PK/PD population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.
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Subject analysis set title |
TEST 2 - PK/PD population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.
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Subject analysis set title |
REF - PK/PD population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.
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Subject analysis set title |
CTR - PK/PD population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.
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End point title |
B17MP Cmax | ||||||||||||||||||||
End point description |
The value and time of the maximum drug concentration (Cmax and tmax) were indicators for the rate of absorption.
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End point type |
Primary
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End point timeframe |
At Visit 2, Visit 3 and Visit 4
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Statistical analysis title |
TEST 1 vs REF | ||||||||||||||||||||
Comparison groups |
TEST 1 - PK/PD population v REF - PK/PD population
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Number of subjects included in analysis |
57
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [1] | ||||||||||||||||||||
Method |
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Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
84.38
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Confidence interval |
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level |
90% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
70.22 | ||||||||||||||||||||
upper limit |
101.38 | ||||||||||||||||||||
Notes [1] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects. |
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Statistical analysis title |
TEST 2 vs REF | ||||||||||||||||||||
Comparison groups |
TEST 2 - PK/PD population v REF - PK/PD population
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Number of subjects included in analysis |
58
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [2] | ||||||||||||||||||||
Method |
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Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
97
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Confidence interval |
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level |
90% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
80.92 | ||||||||||||||||||||
upper limit |
116.27 | ||||||||||||||||||||
Notes [2] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects. |
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Statistical analysis title |
TEST 2 vs TEST 1 | ||||||||||||||||||||
Comparison groups |
TEST 1 - PK/PD population v TEST 2 - PK/PD population
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Number of subjects included in analysis |
57
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [3] | ||||||||||||||||||||
Method |
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Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
114.96
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Confidence interval |
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level |
90% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
95.67 | ||||||||||||||||||||
upper limit |
138.13 | ||||||||||||||||||||
Notes [3] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects |
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Statistical analysis title |
TEST 1 vs CTR | ||||||||||||||||||||
Comparison groups |
TEST 1 - PK/PD population v CTR - PK/PD population
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Number of subjects included in analysis |
58
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence [4] | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
90.83
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
90% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
72.46 | ||||||||||||||||||||
upper limit |
113.84 | ||||||||||||||||||||
Notes [4] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects |
|
|||||||||||||||||||||
End point title |
B17MP AUC0-t | ||||||||||||||||||||
End point description |
After single administration, the area under the plasma concentration versus time curve up to the last quantifiable concentration (AUC0-t) was used to measure the extent of absorption.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
At Visit 2, Visit 3 and Visit 4
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
TEST 1 vs REF | ||||||||||||||||||||
Comparison groups |
TEST 1 - PK/PD population v REF - PK/PD population
|
||||||||||||||||||||
Number of subjects included in analysis |
57
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence [5] | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
91.69
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
90% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
81.64 | ||||||||||||||||||||
upper limit |
102.97 | ||||||||||||||||||||
Notes [5] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
TEST 2 vs REF | ||||||||||||||||||||
Comparison groups |
TEST 2 - PK/PD population v REF - PK/PD population
|
||||||||||||||||||||
Number of subjects included in analysis |
58
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence [6] | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
89.63
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
90% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
79.93 | ||||||||||||||||||||
upper limit |
100.5 | ||||||||||||||||||||
Notes [6] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
TEST 2 vs TEST 1 | ||||||||||||||||||||
Comparison groups |
TEST 1 - PK/PD population v TEST 2 - PK/PD population
|
||||||||||||||||||||
Number of subjects included in analysis |
57
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence [7] | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
97.76
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
90% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
87.05 | ||||||||||||||||||||
upper limit |
109.78 | ||||||||||||||||||||
Notes [7] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects. |
|||||||||||||||||||||
Statistical analysis title |
TEST 1 vs CTR | ||||||||||||||||||||
Comparison groups |
TEST 1 - PK/PD population v CTR - PK/PD population
|
||||||||||||||||||||
Number of subjects included in analysis |
58
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence [8] | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
adjusted geometric means ratio | ||||||||||||||||||||
Point estimate |
90.14
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
90% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
78.39 | ||||||||||||||||||||
upper limit |
103.65 | ||||||||||||||||||||
Notes [8] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects. |
|
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Adverse events information
|
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Timeframe for reporting adverse events |
At each clinic visit from Visit 0 (pre-screening visit) to follow-up (phone call)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
|
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Reporting groups
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Reporting group title |
TEST1
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Reporting group description |
TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI (total dose of BDP 400 μg / FF 24 μg); | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TEST2
|
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Reporting group description |
TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using the AeroChamber Plus™ spacer device (total dose of BDP 400 μg / FF 24 μg); | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
REF treatment
|
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Reporting group description |
REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI (total dose of BDP 400 μg + FF 24 μg); | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CTR Adults
|
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Reporting group description |
CTR: 4 puffs of a fixed combination CHF 1535 100/6 pMDI (total dose of BDP 400 μg / FF 24 μg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 3.3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
There are no limitations nor caveats applicable to this summary of results. |