Clinical Trial Results:
The effect of glycopyrroniumbromide on nocturnal clozapine induced sialorrhea in psychiatric patients: a randomized, cross-over, double blind, placebo controlled trial with an extended open label phase (QUITSPIT study)

Trial information Top of page
Trial identification
Sponsor protocol code	FIO11-05
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Universitair Medisch Centrum Utrecht
Sponsor organisation address	Heidelberglaan 100, Utrecht, Netherlands,
Public contact	Ziekenhuisapotheek UMC Utrecht, Universitair Medisch Centrum Utrecht, 0031 887557218, I.Wilting@umcutrecht.nl
Scientific contact	Ziekenhuisapotheek UMC Utrecht, Universitair Medisch Centrum Utrecht, 0031 887557218, I.Wilting@umcutrecht.nl
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	20 Jun 2015
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	20 Jun 2015
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To determine the effect of oral glycopyrroniumbromide in comparison with placebo on the severity of nocturnal sialorrhea in psychiatric patients treated with clozapine
Protection of trial subjects	Outsome measures were collected during limited amount of visits. Any possible adverse events were monitored during the weekly patient visits using documentated questionairies
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	01 Sep 2012
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Netherlands: 32
Worldwide total number of subjects	32
EEA total number of subjects	32
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)	32
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	Stable users of clozapine using an unchanged clozapine dose for at least 1 month prior to start of the trial. In addition, these subjects were experiencing clozapine induced sialorrhea.
Period 1
Period 1 title	Cross-over 1
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor
Arms
Are arms mutually exclusive	No
Arm title	Glycopyrrolate 1mg
Arm description	Subjects within this arm used glycopyrrolate 1mg/day during 6 days
Arm type	Experimental
Investigational medicinal product name	Glycopyrrolate
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral liquid
Routes of administration	Oral use
Dosage and administration details	Subjects within this arm used glycopyrrolate 1mg/day using 0.2mg/ml oral solution during 6 days
Arm title	Placebo
Arm description	Subjects within this arm used placebo during 6 days
Arm type	Placebo
Investigational medicinal product name	Placebo solution
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral solution
Routes of administration	Oral use
Dosage and administration details	Subjects within this arm used 5 ml of the placebo solution during 6 days
Number of subjects in period 1 Glycopyrrolate 1mg Placebo Started 16 16 Completed 16 16
Period 2
Period 2 title	Wash-out 1
Is this the baseline period?	No
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Wash-out
Arm description	-
Arm type	No intervention
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 2 Wash-out Started 32 Completed 32
Period 3
Period 3 title	Cross-over 2
Is this the baseline period?	No
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor
Arms
Are arms mutually exclusive	Yes
Arm title	Glycopyrrolate 1mg
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Glycopyrrolate
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral liquid
Routes of administration	Oral use
Dosage and administration details	Subjects within this arm used glycopyrrolate 1mg/day using 0.2mg/ml oral solution during 6 days
Arm title	Placebo
Arm description	-
Arm type	Placebo
Investigational medicinal product name	Placebo solution
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral solution
Routes of administration	Oral use
Dosage and administration details	Subjects within this arm used 5 ml of the placebo solution during 6 days
Number of subjects in period 3 Glycopyrrolate 1mg Placebo Started 16 16 Completed 16 16
Period 4
Period 4 title	Wash-out 2
Is this the baseline period?	No
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Wash out
Arm description	-
Arm type	No intervention
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 4 Wash out Started 32 Completed 23 Not completed 9      Lost to follow-up 9
Period 5
Period 5 title	Open label
Is this the baseline period?	No
Allocation method	Non-randomised - controlled
Blinding used	Not blinded
Arms
Arm title	Glycopyrrolate 2mg
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Glycopyrrolate
Investigational medicinal product code
Other name
Pharmaceutical forms	Oral solution
Routes of administration	Oral use
Dosage and administration details	During the open label phase, subject used 2 mg glycopyrrolate/day during 6 days
Number of subjects in period 5 Glycopyrrolate 2mg Started 23 Completed 23

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Cross-over 1
Reporting group description	-
Reporting group values Cross-over 1 Total Number of subjects 32 32 Age categorical Units: Subjects     Adults (18-65 years) 32 32 Gender categorical Units: Subjects     Female 11 11     Male 21 21

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Glycopyrrolate 1mg
Reporting group description	Subjects within this arm used glycopyrrolate 1mg/day during 6 days
Reporting group title	Placebo
Reporting group description	Subjects within this arm used placebo during 6 days
Reporting group title	Wash-out
Reporting group description	-
Reporting group title	Glycopyrrolate 1mg
Reporting group description	-
Reporting group title	Placebo
Reporting group description	-
Reporting group title	Wash out
Reporting group description	-
Reporting group title	Glycopyrrolate 2mg
Reporting group description	-

End points Top of page

Primary: Clinical improvement of CIS assessed by the Patient Global Impression of Improvement (PGI-I) Top of page
End point title	Clinical improvement of CIS assessed by the Patient Global Impression of Improvement (PGI-I)
End point description
End point type	Primary
End point timeframe	Assesments for the end point were performed after period 3 'cross-over 2' and after period 5 'open label'
End point values Glycopyrrolate 1mg Placebo Glycopyrrolate 1mg Placebo Glycopyrrolate 2mg Number of subjects analysed 16 16 16 16 23 Units: Percentage 0 4 2 2 10
Statistical analysis title	McNemar’s test
Comparison groups	Placebo v Glycopyrrolate 1mg v Glycopyrrolate 1mg v Placebo v Glycopyrrolate 2mg
Number of subjects included in analysis	87
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.05
Method	Mcnemar
Parameter type	Risk ratio (RR)
Point estimate	6.96
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	20.36

Primary: Clinical improvement of CIS assessed by the Patient Global Impression of Improvement (PGI-I) Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	adverse events assesments were performed after each period
Adverse event reporting additional description	Adverse events of glycopyrrolate, in terms of worsening of baseline events were assessed
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	other
Dictionary version	1
Reporting groups
Reporting group title	Glycopyrrolate 1mg
Reporting group description	Subjects within this arm used glycopyrrolate 1mg/day during 6 days
Reporting group title	Placebo
Reporting group description	Subjects within this arm used placebo during 6 days
Serious adverse events Glycopyrrolate 1mg Placebo Total subjects affected by serious adverse events      subjects affected / exposed 0 / 32 (0.00%) 0 / 32 (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: 5%
Non-serious adverse events Glycopyrrolate 1mg Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 5 / 32 (15.63%) 5 / 32 (15.63%) Vascular disorders Orthostatic hypotension      subjects affected / exposed 3 / 32 (9.38%) 2 / 32 (6.25%)      occurrences all number 3 2 Nervous system disorders Shortened sleep      subjects affected / exposed 2 / 32 (6.25%) 1 / 32 (3.13%)      occurrences all number 2 1 General disorders and administration site conditions Headache      subjects affected / exposed 2 / 32 (6.25%) 2 / 32 (6.25%)      occurrences all number 2 2 Social circumstances Nervousness      subjects affected / exposed 1 / 32 (3.13%) 2 / 32 (6.25%)      occurrences all number 1 2 Endocrine disorders Diaphoresis      subjects affected / exposed 3 / 32 (9.38%) 2 / 32 (6.25%)      occurrences all number 3 2 Metabolism and nutrition disorders Xerostomia      subjects affected / exposed 2 / 32 (6.25%) 2 / 32 (6.25%)      occurrences all number 2 2

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
Online references
http://www.ncbi.nlm.nih.gov/pubmed/28129312

More information Top of page