Clinical Trial Results:
Palatability testing of a new paediatric formulation of valacyclovir for the prophylaxis and treatment of VZV and HSV infections in children – VALID 0
Summary
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EudraCT number |
2012-000577-22 |
Trial protocol |
NL |
Global end of trial date |
30 Mar 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Nov 2020
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First version publication date |
19 Nov 2020
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Other versions |
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Summary report(s) |
paper |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AKF-UMCN11.05
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid 10, Nijmegen, Netherlands,
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Public contact |
David Burger, Radboud University Nijmegen Medical Centre, 31 243616405, d.bastiaans@akf.umcn.nl
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Scientific contact |
Diane Bastiaans, Radboud University Nijmegen Medical Centre, 31 243616405, david.burger@radboudumc.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jun 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Mar 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Mar 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine which of three newly developed formulations of valacyclovir is accepted best in children.
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Protection of trial subjects |
The burden of this study is very low: a single dose, or less, exposure to pharmaceutical active substance. The substance has solely antiviral activity and therefore does not influence normal physiological processes in the human body.
The total dose of the drug that will be administered to the subject during one taste assessment is 270 mg (4 ml of the 20 mg/ml solution, the 25 mg/ml suspension and the mixed formulation (22.5 mg/ml)) for children of 4-8 years and 540 mg for children of 8-12 years and the parent(s).
The dose of valacyclovir in immunocompromised children for the treatment of VZV and HSV infection is 60-90 mg/kg daily, divided in two to three doses. The estimated bodyweight of a child of 4 years of age is 15-19 kg and for a child of 8 years of age 25-28 kg. The lowest single therapeutic dose would be 300 mg (15 kg * 20 mg/kg). For children 4-8 years of age the administered dose during the taste assessment (270 mg) is comparable to a single therapeutic dose and less than 1/3 of a total daily therapeutic dose for a child of 15 kg. For children 8-12 years of age the dose administered (540 mg) is comparable to a single therapeutic dose for a child of 27 kg, and 1/3 or less of a total daily therapeutic dose.
The taste assessment will be performed combined with a regular visit to the outpatient clinic. Subjects don’t have to come to the hospital separately to participate in this study.
DNA will be collected through obtaining a 2 ml saliva sample. This is a non-invasive and patient friendly way of obtaining DNA.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Aug 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 64
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Worldwide total number of subjects |
64
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EEA total number of subjects |
64
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
33
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
31
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
30 children and their parent(s). Inclusion criteria: 1. Subject is at least 4 years of age. 2. Subject weighs at least 15 kg. 3. Subject is capable of performing the taste assessment, according to the investigator’s judgement. 4. The child and parent(s) are willing to participate in the taste assessment. 5. Signed informed consent | |||||||||||||||
Pre-assignment
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Screening details |
No tests have to be performed to decide whether the subject is allowed to participate in the taste assessment. The capability to perform the palatability testing is judged by the investigator. The investigator will also determine whether the in- and exclusion criteria are met. | |||||||||||||||
Period 1
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Period 1 title |
treatment (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
The subject performing the taste assessment cannot be fully blinded for the different formulations, since the appearance of a solution and suspension is different. All formulations will be presented in similar plastic medication cups. The investigator is not blinded, because in case of spillage, solution can be replaced.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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test | |||||||||||||||
Arm description |
20 mg/ml valacyclovir solution | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
valacyclovir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Children of 4-8 years will taste 4 ml of each solution and children of 8-12 years and the parent(s) will taste 8 ml of each solution.
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Arm title
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reference | |||||||||||||||
Arm description |
20 mg/ml valacyclovir solution from crushed tablets | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
valacyclovir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Crushed and suspended tablet. Children of 4-8 years will taste 4 ml of each solution and children of 8-12 years and the parent(s) will taste 8 ml of each solution.
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Baseline characteristics reporting groups
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Reporting group title |
treatment
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
evaluable
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
evaluable child parent pairs
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End points reporting groups
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Reporting group title |
test
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Reporting group description |
20 mg/ml valacyclovir solution | ||
Reporting group title |
reference
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Reporting group description |
20 mg/ml valacyclovir solution from crushed tablets | ||
Subject analysis set title |
evaluable
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
evaluable child parent pairs
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End point title |
VAS score [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
entire study, 1 day
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: only descriptive difference was reported, no formal test was done |
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Notes [2] - children only [3] - results of children only |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
entire study
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Assessment type |
Non-systematic | ||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
none | ||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
ae group
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Reporting group description |
- | ||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||
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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: only very limited exposure to medication, no adverse events were reported |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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08 Mar 2013 |
1. Change from single centre to multicentre study.
2. Include two additional investigators to the list.
3. Adding description of a specific group of children that can be included.
4. Further clarify the exclusion criteria.
5. Minor changes |
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12 Dec 2014 |
1. Restart of the trial
2. Addition of second phase of the trial
In the first phase of the trial, children and one of their parents tested three newly developed, saccharose based, formulations. Twelve children and one of their parents were included into the first phase of this trial, of which 8 had evaluable data. In the second phase of the trial, two different valacyclovir liquids will be tested: one newly developed, glycerol based formulation (solution, concentration 20 mg/mL) and a reference formulation (suspension, concentration 25 mg/mL).
3. Change of primary objective in the second phase of the trial
4. Changes in trial set-up
5. Addition of secondary objective |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
Only the VAS results for the children were reported, this template does not allow for two different groups. | |||||||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/28800385 |