Clinical Trial Results:
A double blind, randomised, placebo-controlled, crossover study assessing the use of XEN D0103 in patients with paroxysmal atrial fibrillation and implanted pacemakers allowing continuous beat-to-beat monitoring of drug efficacy

Trial information Top of page
Trial identification
Sponsor protocol code	XEN-D0103-CL-05
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Xention Ltd.
Sponsor organisation address	Unit 5, Quern House, Hinton Way, Great Shelford, United Kingdom, CB22 5LD
Public contact	Chief Medical Officer, Xention Limited, + 44 1223493900, info@xention.com
Scientific contact	Chief Medical Officer, Xention Limited, + 44 1223493900, info@xention.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	14 May 2015
Is this the analysis of the primary completion data?	Yes
Primary completion date	14 May 2015
Global end of trial reached?	Yes
Global end of trial date	14 May 2015
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To assess the reduction in AF burden (time spent in AF as a proportion of the analysis period) by XEN-D0103 (50 mg BID) compared to placebo in patients with paroxysmal AF.
Protection of trial subjects	No specific measures required.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	23 May 2014
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	United Kingdom: 21
Worldwide total number of subjects	21
EEA total number of subjects	21
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)	1
From 65 to 84 years	19
85 years and over	1

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	Screening procedures 42 to 14 days before 1st dose of study drug (XEN-D103/Placebo).
Period 1
Period 1 title	Overall Period
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Data analyst
Arms
Are arms mutually exclusive	No
Arm title	Group 1
Arm description	Subjects received 2 capsules Xen-D103 50 mg daily for 28 days
Arm type	Experimental
Investigational medicinal product name	XEN-D103
Investigational medicinal product code	XEN-D103
Other name
Pharmaceutical forms	Capsule
Routes of administration	Oral use
Dosage and administration details	Subjects received XEN-D103 50mg 2 capsules daily for 28 days.
Arm title	Group 2
Arm description	Subjects received Placebo 2 capsules daily for 28 days
Arm type	Experimental
Investigational medicinal product name	Placebo
Investigational medicinal product code	Placebo
Other name
Pharmaceutical forms	Capsule
Routes of administration	Oral use
Dosage and administration details	Subjects received 2 capsules placebo daily for 28 days
Number of subjects in period 1 Group 1 Group 2 Started 21 21 Completed 21 21

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall Period
Reporting group description	-
Reporting group values Overall Period Total Number of subjects 21 21 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) 1 1     From 65-84 years 19 19     85 years and over 1 1 Gender categorical Units: Subjects     Female 8 8     Male 13 13

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Group 1
Reporting group description	Subjects received 2 capsules Xen-D103 50 mg daily for 28 days
Reporting group title	Group 2
Reporting group description	Subjects received Placebo 2 capsules daily for 28 days

End points Top of page

Primary: Time spent in AF as a proportion of the analysis period Top of page
End point title	Time spent in AF as a proportion of the analysis period
End point description
End point type	Primary
End point timeframe	Baseline to 56 days
End point values Group 1 Group 2 Number of subjects analysed 21 21 Units: percent     arithmetic mean (standard deviation) 19.5 ( 25.7 ) 17.2 ( 20.6 )
Statistical analysis title	Generalised Mixed Model
Statistical analysis description	Generalised Mixed Model of Log Transformed AF burden with treatment and period as fixed effects and patient as a random effect intercept term.
Comparison groups	Group 1 v Group 2
Number of subjects included in analysis	42
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.77
Method	Mixed models analysis
Parameter type	ratio of adjusted geometric Means
Point estimate	1.01
Confidence interval
level	90%
sides	2-sided
lower limit	0.98
upper limit	1.05

Primary: Time spent in AF as a proportion of the analysis period Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From the time of informed consent through the to the last visit.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	17.0
Reporting groups
Reporting group title	Group 1
Reporting group description	-
Reporting group title	Group 2
Reporting group description	-
Serious adverse events Group 1 Group 2 Total subjects affected by serious adverse events      subjects affected / exposed 0 / 10 (0.00%) 0 / 11 (0.00%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 0
Frequency threshold for reporting non-serious adverse events: 0.05%
Non-serious adverse events Group 1 Group 2 Total subjects affected by non serious adverse events      subjects affected / exposed 6 / 10 (60.00%) 10 / 11 (90.91%) Gastrointestinal disorders Diarrhoea      subjects affected / exposed 1 / 10 (10.00%) 3 / 11 (27.27%)      occurrences all number 1 1 Abdominal pain upper      subjects affected / exposed 1 / 10 (10.00%) 0 / 11 (0.00%)      occurrences all number 1 0 Constipation      subjects affected / exposed 0 / 10 (0.00%) 1 / 11 (9.09%)      occurrences all number 0 1 Vomiting      subjects affected / exposed 0 / 10 (0.00%) 1 / 11 (9.09%)      occurrences all number 0 1 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 1 / 10 (10.00%) 0 / 11 (0.00%)      occurrences all number 1 0 Infections and infestations Upper respiratory tract infection      subjects affected / exposed 0 / 10 (0.00%) 2 / 11 (18.18%)      occurrences all number 0 2 Lower respiratory tract infection      subjects affected / exposed 1 / 10 (10.00%) 0 / 11 (0.00%)      occurrences all number 1 0 Cellulitis      subjects affected / exposed 1 / 10 (10.00%) 0 / 11 (0.00%)      occurrences all number 1 0 Ear infection      subjects affected / exposed 1 / 10 (10.00%) 0 / 11 (0.00%)      occurrences all number 1 0 Influenza      subjects affected / exposed 0 / 10 (0.00%) 1 / 11 (9.09%)      occurrences all number 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.
None reported

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