Clinical Trial Results:
A randomised, double-blind, double-dummy, multi-site, phase III, single dose, 4-way cross-over pharmacodynamic study evaluating the efficacy of Bricanyl Turbuhaler M3 compared to Bricanyl Turbuhaler M2 by studying the protective effect on methacholine induced bronchoconstriction in patients with stable, mild to moderate asthma

Trial information Top of page
Trial identification
Sponsor protocol code	D4711C00001
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	AstraZeneca R&D Gothenburg
Sponsor organisation address	SE-431 83, Mölndal, Sweden,
Public contact	Göran Eckerwall, MD, PhD, AstraZeneca R&D, goran.eckerwall@astrazeneca.com
Scientific contact	Göran Eckerwall, MD, PhD, AstraZeneca R&D, goran.eckerwall@astrazeneca.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
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?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	25 Apr 2016
Is this the analysis of the primary completion data?	Yes
Primary completion date	05 Nov 2015
Global end of trial reached?	Yes
Global end of trial date	05 Nov 2015
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	The primary objective is to demonstrate therapeutic equivalence between Bricanyl Turbuhaler M3 and Bricanyl Turbuhaler M2 using bronchoprotective effect as outcome measure. Outcome measurements: PC20 (Methacholine provocative concentration causing a 20% drop in FEV1)
Protection of trial subjects	Prior methacholine challenge a stable asthma condition was ensured by FEV1 at every visit. Signs and symptoms were recorded and the challenge stopped after a 20% fall in FEV1 was reached. Ipratroprium was given post challenge.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	10 Mar 2015
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	Canada: 35
Country: Number of subjects enrolled	Netherlands: 10
Country: Number of subjects enrolled	Sweden: 15
Worldwide total number of subjects	60
EEA total number of subjects	25
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)	0
Adults (18-64 years)	60
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients with stable, mild to moderate asthma were enrolled. The first patient entered the study on 10 March 2015 and the last patient completed the study on 5 November 2015. Subjects were recruited from: Site 1001 and 1002 in Canada, Site 7201 in Sweden,and Site 5001 in the Netherlands.
Pre-assignment
Screening details	Of the 95 patients enrolled 34 were screen failures mainly due to not fulfilling specific randomization criteria on stability in asthma or sensitivity to methacholine challenge; 1 was withdrawal by subject; 72 entered run in period. A total of 60 patients were randomized to the 4 single-dose treatments with terbutaline in a crossover design.
Period 1
Period 1 title	Visit 3
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Carer, Data analyst, Assessor
Arms
Are arms mutually exclusive	Yes
Arm title	M2 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M2 Turbuhaler
Arm title	M2 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M2 Turbuhaler
Arm title	M3 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M3 Turbuhaler
Arm title	M3 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M3 Turbuhaler
Number of subjects in period 1 M2 0.5 mg M2 1.5 mg M3 0.5 mg M3 1.5 mg Started 15 15 14 16 Completed 15 15 14 16
Period 2
Period 2 title	Visit 4
Is this the baseline period?	No
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Carer, Data analyst, Assessor
Arms
Are arms mutually exclusive	Yes
Arm title	M2 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M2 Turbuhaler
Arm title	M2 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M2 Turbuhaler
Arm title	M3 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M3 Turbuhaler
Arm title	M3 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M3 Turbuhaler
Number of subjects in period 2 M2 0.5 mg M2 1.5 mg M3 0.5 mg M3 1.5 mg Started 15 14 16 15 Completed 15 14 16 15
Period 3
Period 3 title	Visit 5
Is this the baseline period?	No
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Carer, Data analyst, Assessor
Arms
Are arms mutually exclusive	Yes
Arm title	M2 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M2 Turbuhaler
Arm title	M2 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M2 Turbuhaler
Arm title	M3 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M3 Turbuhaler
Arm title	M3 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M3 Turbuhaler
Number of subjects in period 3 M2 0.5 mg M2 1.5 mg M3 0.5 mg M3 1.5 mg Started 16 15 15 14 Completed 16 15 15 14
Period 4
Period 4 title	Visit 6
Is this the baseline period?	No
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Carer, Data analyst, Assessor
Arms
Are arms mutually exclusive	Yes
Arm title	M2 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M2 Turbuhaler
Arm title	M2 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M2
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M2 Turbuhaler
Arm title	M3 0.5 mg
Arm description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	0.5 mg M3 Turbuhaler
Arm title	M3 1.5 mg
Arm description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Arm type	Active comparator
Investigational medicinal product name	terbutaline sulphate via Turbuhaler M3
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	1.5 mg M3 Turbuhaler
Number of subjects in period 4 M2 0.5 mg M2 1.5 mg M3 0.5 mg M3 1.5 mg Started 14 16 15 15 Completed 14 16 15 15

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Visit 3
Reporting group description	-
Reporting group values Visit 3 Total Number of subjects 60 60 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 60 60     From 65-84 years 0 0     85 years and over 0 0 Age Continuous | Units: years     median (full range (min-max)) 26 (18 to 64) - Gender, Male/Female Gender Units: Participants     Female 40 40     Male 20 20 Race/Ethnicity, Customized Race Units: Subjects     White 57 57     Black or African American 1 1     Asian 2 2
Subject analysis sets
Subject analysis set title	Efficacy Analysis Set
Subject analysis set type	Modified intention-to-treat
Subject analysis set description	All patients who have at least two values of the primary endpoints in the efficacy analysis set.
Subject analysis sets values Efficacy Analysis Set Number of subjects 60 Age categorical Units: Subjects     In utero 0     Preterm newborn infants (gestational age < 37 wks) 0     Newborns (0-27 days) 0     Infants and toddlers (28 days-23 months) 0     Children (2-11 years) 0     Adolescents (12-17 years) 0     Adults (18-64 years) 60     From 65-84 years 0     85 years and over 0 Age Continuous | Units: years     median (full range (min-max)) 26 (18 to 64) Gender, Male/Female Gender Units: Participants     Female 40     Male 20 Race/Ethnicity, Customized Race Units: Subjects     White 57     Black or African American 1     Asian 2

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	M2 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M2 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M3 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M3 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M2 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M2 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M3 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M3 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M2 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M2 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M3 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M3 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M2 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M2 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M3 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M3 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Subject analysis set title	Efficacy Analysis Set
Subject analysis set type	Modified intention-to-treat
Subject analysis set description	All patients who have at least two values of the primary endpoints in the efficacy analysis set.

End points Top of page

Primary: PC20 Top of page
End point title	PC20
End point description
End point type	Primary
End point timeframe	During treatment period from Visit 3 to Visit 6
End point values M2 0.5 mg M2 0.5 mg M2 0.5 mg M2 0.5 mg M2 1.5 mg M2 1.5 mg M2 1.5 mg M2 1.5 mg M3 0.5 mg M3 0.5 mg M3 0.5 mg M3 0.5 mg M3 1.5 mg M3 1.5 mg M3 1.5 mg M3 1.5 mg Number of subjects analysed 15 15 16 14 15 14 15 16 14 16 15 15 16 15 14 15 Units: mg/mL     geometric mean (geometric coefficient of variation) 5.43 ( 302.49 ) 10.03 ( 185.14 ) 11.21 ( 160.36 ) 23.06 ( 341.4 ) 22.76 ( 255.89 ) 37.39 ( 306.96 ) 10.99 ( 164.29 ) 18.01 ( 132.9 ) 17.8 ( 319.32 ) 8.63 ( 106.66 ) 12 ( 237.01 ) 5.44 ( 215.56 ) 19.34 ( 178.83 ) 10.22 ( 199.6 ) 29.04 ( 253.8 ) 17.93 ( 250.8 )
Statistical analysis title	PC20 mixed effect model analysis: M2 1.5 vs M2 0.5
Statistical analysis description	A linear mixed effect model based on restricted maximum likelihood analysis is used to estimate the treatment effect. PC20 in natural log scale is the response variable, treatment and period are the fixed effects, and patient within sequence is a random effect.
Comparison groups	M2 0.5 mg v M2 1.5 mg v M2 0.5 mg v M2 1.5 mg v M2 0.5 mg v M2 1.5 mg v M2 0.5 mg v M2 1.5 mg
Number of subjects included in analysis	120
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.001
Method	Mixed models analysis
Parameter type	Estimated mean ratio
Point estimate	1.87
Confidence interval
level	95%
sides	2-sided
lower limit	1.52
upper limit	2.29
Statistical analysis title	PC20 mixed effect model analysis: M3 1.5 vs M3 0.5
Statistical analysis description	A linear mixed effect model based on restricted maximum likelihood analysis is used to estimate the treatment effect. PC20 in natural log scale is the response variable, treatment and period are the fixed effects, and patient within sequence is a random effect.
Comparison groups	M3 0.5 mg v M3 1.5 mg v M3 0.5 mg v M3 1.5 mg v M3 0.5 mg v M3 1.5 mg v M3 0.5 mg v M3 1.5 mg
Number of subjects included in analysis	120
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.001
Method	Mixed models analysis
Parameter type	Estimated mean ratio
Point estimate	1.79
Confidence interval
level	95%
sides	2-sided
lower limit	1.46
upper limit	2.2
Statistical analysis title	PC20 mixed effect model analysis: M3 0.5 vs M2 0.5
Statistical analysis description	A linear mixed effect model based on restricted maximum likelihood analysis is used to estimate the treatment effect. PC20 in natural log scale is the response variable, treatment and period are the fixed effects, and patient within sequence is a random effect.
Comparison groups	M2 0.5 mg v M3 0.5 mg v M2 0.5 mg v M3 0.5 mg v M2 0.5 mg v M3 0.5 mg v M2 0.5 mg v M3 0.5 mg
Number of subjects included in analysis	120
Analysis specification	Pre-specified
Analysis type	equivalence
Method	Mixed models analysis
Parameter type	Estimated mean ratio
Point estimate	0.92
Confidence interval
level	95%
sides	2-sided
lower limit	0.75
upper limit	1.13
Statistical analysis title	PC20 mixed effect model analysis: M3 1.5 vs M2 1.5
Statistical analysis description	A linear mixed effect model based on restricted maximum likelihood analysis is used to estimate the treatment effect. PC20 in natural log scale is the response variable, treatment and period are the fixed effects, and patient within sequence is a random effect.
Comparison groups	M2 1.5 mg v M3 1.5 mg v M2 1.5 mg v M3 1.5 mg v M2 1.5 mg v M3 1.5 mg v M2 1.5 mg v M3 1.5 mg
Number of subjects included in analysis	120
Analysis specification	Pre-specified
Analysis type	equivalence
Method	Mixed models analysis
Parameter type	Estimated mean ratio
Point estimate	0.88
Confidence interval
level	95%
sides	2-sided
lower limit	0.72
upper limit	1.08

Primary: PC20 Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	During randomized treatment period from Visit 3 to Visit 6
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	18.1
Reporting groups
Reporting group title	M2 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M2
Reporting group title	M3 0.5 mg
Reporting group description	0.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M3 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M3
Reporting group title	M2 1.5 mg
Reporting group description	1.5 mg terbutaline sulphate administered via Turbuhaler M2
Serious adverse events M2 0.5 mg M3 0.5 mg M3 1.5 mg M2 1.5 mg Total subjects affected by serious adverse events      subjects affected / exposed 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (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: 0%
Non-serious adverse events M2 0.5 mg M3 0.5 mg M3 1.5 mg M2 1.5 mg Total subjects affected by non serious adverse events      subjects affected / exposed 12 / 60 (20.00%) 7 / 60 (11.67%) 13 / 60 (21.67%) 10 / 60 (16.67%) Injury, poisoning and procedural complications Arthropod sting      subjects affected / exposed 0 / 60 (0.00%) 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 0 1 0 0 Cardiac disorders Palpitations      subjects affected / exposed 0 / 60 (0.00%) 1 / 60 (1.67%) 2 / 60 (3.33%) 1 / 60 (1.67%)      occurrences all number 0 2 2 1 Tachycardia      subjects affected / exposed 0 / 60 (0.00%) 0 / 60 (0.00%) 1 / 60 (1.67%) 1 / 60 (1.67%)      occurrences all number 0 0 1 1 Nervous system disorders Dysgeusia      subjects affected / exposed 6 / 60 (10.00%) 5 / 60 (8.33%) 7 / 60 (11.67%) 6 / 60 (10.00%)      occurrences all number 6 5 7 6 Headache      subjects affected / exposed 1 / 60 (1.67%) 1 / 60 (1.67%) 1 / 60 (1.67%) 0 / 60 (0.00%)      occurrences all number 1 1 1 0 Sciatica      subjects affected / exposed 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 1 0 0 0 Syncope      subjects affected / exposed 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 1 0 0 0 Tremor      subjects affected / exposed 2 / 60 (3.33%) 1 / 60 (1.67%) 5 / 60 (8.33%) 3 / 60 (5.00%)      occurrences all number 2 1 5 3 General disorders and administration site conditions Chest discomfort      subjects affected / exposed 0 / 60 (0.00%) 0 / 60 (0.00%) 1 / 60 (1.67%) 0 / 60 (0.00%)      occurrences all number 0 0 1 0 Pyrexia      subjects affected / exposed 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 1 0 0 0 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 0 / 60 (0.00%) 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 0 1 0 0 Diarrhoea      subjects affected / exposed 0 / 60 (0.00%) 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 0 1 0 0 Dry mouth      subjects affected / exposed 0 / 60 (0.00%) 0 / 60 (0.00%) 1 / 60 (1.67%) 0 / 60 (0.00%)      occurrences all number 0 0 1 0 Reproductive system and breast disorders Dysmenorrhoea      subjects affected / exposed 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 0 0 1 Psychiatric disorders Restlessness      subjects affected / exposed 0 / 60 (0.00%) 0 / 60 (0.00%) 1 / 60 (1.67%) 1 / 60 (1.67%)      occurrences all number 0 0 1 1 Infections and infestations Nasopharyngitis      subjects affected / exposed 2 / 60 (3.33%) 0 / 60 (0.00%) 1 / 60 (1.67%) 0 / 60 (0.00%)      occurrences all number 2 0 1 0 Sinusitis      subjects affected / exposed 1 / 60 (1.67%) 0 / 60 (0.00%) 0 / 60 (0.00%) 0 / 60 (0.00%)      occurrences all number 1 0 0 0

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.
None reported

More information Top of page