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.

Trial information Top of page
Trial identification
Sponsor protocol code	CCD-1104-PR-0062
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01803087
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Chiesi Farmaceutici S.p.A.
Sponsor organisation address	Via Palermo 26/A, Parma, Italy, 43122
Public contact	Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., Chiesi Farmaceutici S.p.A., +39 0521 2791, ClinicalTrials_info@chiesi.com
Scientific contact	Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., Chiesi Farmaceutici S.p.A., +39 0521 2791, ClinicalTrials_info@chiesi.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	Yes
EMA paediatric investigation plan number(s)	EMEA-000548-PIP01-09
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	Yes
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	22 Mar 2013
Is this the analysis of the primary completion data?	Yes
Primary completion date	24 Aug 2012
Global end of trial reached?	Yes
Global end of trial date	24 Aug 2012
Was the trial ended prematurely?	No
General information about the trial
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.
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.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	21 Feb 2012
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Poland: 60
Worldwide total number of subjects	60
EEA total number of subjects	60
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	30
Adults (18-64 years)	30
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
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
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
Period 1 title	Overall trial by sequence (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Blinding implementation details	As this is an open-label study, blinding is not applicable.
Arms
Are arms mutually exclusive	Yes
Arm title	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
Investigational medicinal product code
Other name	beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
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™
Investigational medicinal product name	beclomethasone dipropionate + formoterol fumarate
Investigational medicinal product code
Other name	BDP, FF
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
Dosage and administration details	Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)
Arm title	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
Investigational medicinal product code
Other name	beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
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™
Investigational medicinal product name	beclomethasone dipropionate + formoterol fumarate
Investigational medicinal product code
Other name	BDP, FF
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
Dosage and administration details	Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)
Arm title	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
Investigational medicinal product code
Other name	beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
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™
Investigational medicinal product name	beclomethasone dipropionate + formoterol fumarate
Investigational medicinal product code
Other name	BDP, FF
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
Dosage and administration details	Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)
Arm title	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
Investigational medicinal product code
Other name	CHF 1535 100/6 pMDI, beclomethasone / formoterol fixed combination
Pharmaceutical forms	Inhalation solution
Routes of administration	Inhalation use
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.
Number of subjects in period 1 TEST 1/REF/TEST 2 TEST 2/TEST 1/REF REF/TEST 2/TEST 1 CONTROL Started 10 10 10 30 Completed 9 10 10 30 Not completed 1 0 0 0      Protocol deviation 1 - - -

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	TEST 1/REF/TEST 2
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
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
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
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.
Reporting group values TEST 1/REF/TEST 2 TEST 2/TEST 1/REF REF/TEST 2/TEST 1 CONTROL Total Number of subjects 10 10 10 30 60 Age categorical Units: Subjects     Adolescents (12-17 years) 10 10 10 0 30     Adults (18-64 years) 0 0 0 30 30 Age continuous Units: years     median (full range (min-max)) 16 (12 to 17) 14 (12 to 17) 16 (12 to 16) 40 (18 to 64) - Gender categorical Note: The sequence TEST 1/REF/ TEST 2 included one subject who discontinued the study due to a major protocol deviation. Units: Subjects     Female 6 5 5 14 30     Male 4 5 5 16 30

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	TEST 1/REF/TEST 2
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
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
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
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
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.
Subject analysis set title	TEST 2 - PK/PD population
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.
Subject analysis set title	REF - PK/PD population
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.
Subject analysis set title	CTR - PK/PD population
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.

End points Top of page

Primary: B17MP Cmax Top of page
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.
End point type	Primary
End point timeframe	At Visit 2, Visit 3 and Visit 4
End point values TEST 1 - PK/PD population TEST 2 - PK/PD population REF - PK/PD population CTR - PK/PD population Number of subjects analysed 28 29 29 30 Units: pg/mL     arithmetic mean (standard deviation) 1056 ( 1137 ) 1044 ( 439 ) 1116 ( 508 ) 1052 ( 465 )
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 [1]
Method
Parameter type	adjusted geometric means ratio
Point estimate	84.38
Confidence interval
level	90%
sides	2-sided
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.
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 [2]
Method
Parameter type	adjusted geometric means ratio
Point estimate	97
Confidence interval
level	90%
sides	2-sided
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.
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 [3]
Method
Parameter type	adjusted geometric means ratio
Point estimate	114.96
Confidence interval
level	90%
sides	2-sided
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
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 [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

Primary: B17MP Cmax Top of page

Primary: B17MP AUC0-t Top of page
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
End point values TEST 1 - PK/PD population TEST 2 - PK/PD population REF - PK/PD population CTR - PK/PD population Number of subjects analysed 28 29 29 30 Units: pg.h/mL     arithmetic mean (standard deviation) 2798 ( 846 ) 2724 ( 957 ) 3028 ( 965 ) 3107 ( 980 )
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.

Primary: B17MP AUC0-t Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	At each clinic visit from Visit 0 (pre-screening visit) to follow-up (phone call)
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	14.1
Reporting groups
Reporting group title	TEST1
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
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
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
Reporting group description	CTR: 4 puffs of a fixed combination CHF 1535 100/6 pMDI (total dose of BDP 400 μg / FF 24 μg).
Serious adverse events TEST1 TEST2 REF treatment CTR Adults Total subjects affected by serious adverse events      subjects affected / exposed 0 / 30 (0.00%) 0 / 29 (0.00%) 0 / 29 (0.00%) 0 / 30 (0.00%)      number of deaths (all causes) 0 0 0 0      number of deaths resulting from adverse events 0 0 0 0
Frequency threshold for reporting non-serious adverse events: 3.3%
Non-serious adverse events TEST1 TEST2 REF treatment CTR Adults Total subjects affected by non serious adverse events      subjects affected / exposed 1 / 30 (3.33%) 1 / 29 (3.45%) 3 / 29 (10.34%) 4 / 30 (13.33%) Nervous system disorders Headache      subjects affected / exposed 0 / 30 (0.00%) 1 / 29 (3.45%) 0 / 29 (0.00%) 1 / 30 (3.33%)      occurrences all number 0 1 0 1 Tremor      subjects affected / exposed 0 / 30 (0.00%) 0 / 29 (0.00%) 2 / 29 (6.90%) 0 / 30 (0.00%)      occurrences all number 0 0 2 0 Ear and labyrinth disorders Vertigo      subjects affected / exposed 0 / 30 (0.00%) 0 / 29 (0.00%) 0 / 29 (0.00%) 2 / 30 (6.67%)      occurrences all number 0 0 0 2 Gastrointestinal disorders Abdominal pain upper      subjects affected / exposed 1 / 30 (3.33%) 0 / 29 (0.00%) 0 / 29 (0.00%) 0 / 30 (0.00%)      occurrences all number 1 0 0 0 Nausea      subjects affected / exposed 0 / 30 (0.00%) 1 / 29 (3.45%) 0 / 29 (0.00%) 0 / 30 (0.00%)      occurrences all number 0 1 0 0 Vomiting      subjects affected / exposed 0 / 30 (0.00%) 1 / 29 (3.45%) 0 / 29 (0.00%) 0 / 30 (0.00%)      occurrences all number 0 1 0 0 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 0 / 30 (0.00%) 0 / 29 (0.00%) 0 / 29 (0.00%) 1 / 30 (3.33%)      occurrences all number 0 0 0 1

Adverse events Top of page

More information Top of page
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.

More information Top of page