Clinical Trial Results:
Effect of methylnaltrexone on intragastric pressure, the occurrence of transient lower esophageal sphincter relaxations and reflux events in healthy subjects: a double-blind, placebo-controlled, randomized, cross-over study

Trial information Top of page
Trial identification
Sponsor protocol code	Methylnaltrexone2016
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	TARGID
Sponsor organisation address	Herestraat 49, Leuven, Belgium, 3000
Public contact	TARGID, K.U. Leuven, 32 16344225, jan.tack@kuleuven.be
Scientific contact	TARGID, K.U. Leuven, 32 16344225, jan.tack@kuleuven.be
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	03 Feb 2016
Is this the analysis of the primary completion data?	Yes
Primary completion date	12 Oct 2015
Global end of trial reached?	Yes
Global end of trial date	12 Oct 2015
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To investigate the effect of methylnaltrexone on intragastric pressure, the occurrence of transient lower esophageal sphincter relaxations and reflux events in healthy subjects
Protection of trial subjects	Identification of trial subjects was protected by implementation of subject numbers.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	23 Jun 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	Belgium: 15
Worldwide total number of subjects	15
EEA total number of subjects	15
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)	15
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	Healthy volunteers were included in this study
Period 1
Period 1 title	Overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Single blind
Roles blinded	Subject
Arms
Are arms mutually exclusive	No
Arm title	Methylnaltrexone subcutaneous + placebo infusion
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Methylnaltrexone
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection
Routes of administration	Subcutaneous use
Dosage and administration details	subcutaneous injection of 12 mg methylnaltrexone (Relistor®; Wyeth Pharmaceucals, Louvain- la- Neuve, Belgium; 0.6 mL)
Investigational medicinal product name	Saline solution
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	intravenous infusion of saline (bolus injecton of 1 mL followed by a continuous infusion of 100 mL/h),
Arm title	Methylnaltrexone subcutaneous + naloxone infusion
Arm description	-
Arm type	Active comparator
Investigational medicinal product name	Methylnaltrexone
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection
Routes of administration	Subcutaneous use
Dosage and administration details	subcutaneous injection of 12 mg methylnaltrexone (Relistor®; Wyeth Pharmaceucals, Louvain- la- Neuve, Belgium; 0.6 mL)
Investigational medicinal product name	Naloxone
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	intravenous infusion of naloxone (0.4 mg intravenous bolus [1 mL] followed by continuous infusion 20 μg/kg/h [100 mL/h]; ‘Narcan’, Bristol- Myers Squibb Pharma, Braine- l’Alleud, Belgium
Arm title	Placebo subcutaneous + placebo infusion
Arm description	-
Arm type	Placebo
Investigational medicinal product name	Saline solution
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	intravenous infusion of saline (bolus injecton of 1 mL followed by a continuous infusion of 100 mL/h),
Investigational medicinal product name	Saline solution
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for injection
Routes of administration	Subcutaneous use
Dosage and administration details	subcutaneous injection of saline
Number of subjects in period 1 Methylnaltrexone subcutaneous + placebo infusion Methylnaltrexone subcutaneous + naloxone infusion Placebo subcutaneous + placebo infusion Started 15 15 15 Completed 15 15 15

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall trial (overall period)
Reporting group description	-
Reporting group values Overall trial (overall period) Total Number of subjects 15 15 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) 15 15     From 65-84 years 0 0     85 years and over 0 0 Age continuous Units: years     arithmetic mean (full range (min-max)) 34.1 (18 to 42) - Gender categorical Units: Subjects     Female 9 9     Male 6 6

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Methylnaltrexone subcutaneous + placebo infusion
Reporting group description	-
Reporting group title	Methylnaltrexone subcutaneous + naloxone infusion
Reporting group description	-
Reporting group title	Placebo subcutaneous + placebo infusion
Reporting group description	-

End points Top of page

Primary: Number of TLESRs Top of page
End point title	Number of TLESRs
End point description
End point type	Primary
End point timeframe	Comparison between three conditions
End point values Methylnaltrexone subcutaneous + placebo infusion Methylnaltrexone subcutaneous + naloxone infusion Placebo subcutaneous + placebo infusion Number of subjects analysed 15 15 15 Units: Number of TLESRs     arithmetic mean (standard deviation) 7.2 ( 1.3 ) 7.3 ( 1.6 ) 8.6 ( 1.3 )
Statistical analysis title	ANOVA number of TLESRs
Comparison groups	Methylnaltrexone subcutaneous + naloxone infusion v Methylnaltrexone subcutaneous + placebo infusion v Placebo subcutaneous + placebo infusion
Number of subjects included in analysis	45
Analysis specification	Pre-specified
Analysis type	equivalence
P-value	< 0.05
Method	ANOVA
Confidence interval

Primary: Number of TLESRs Top of page

Adverse events Top of page
Adverse events information [1]
Timeframe for reporting adverse events	From signing the informed consent until the end of the last study visit
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	23
Frequency threshold for reporting non-serious adverse events: 5%
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Hunger was reported in the three different conditions. Hunger was caused by the study protocol (subjects needed to be fasted durng the study visits) and not due to the study medication

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