PrimaryTo determine whether the palatability of a newly developed formulation of valacyclovir is non-inferior to administration of crushed and suspended tablets in children, is the primary objective of the second phase of the trial.The primary…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A 100 mm facial hedonic scale will be employed to indicate the palatability of
each formulation.
Secondary outcome
For (one of) the parents a 100 mm facial hedonic scale will be employed to
indicate the palatability of each formulation. They will also fill in a
questionnaire to determine which of the formulations they think will have the
preference of their child. Also, they have to fill in what basic taste they
taste.
Background summary
In children acyclovir is used as prophylaxis and treatment of varicella zoster
virus (VZV) and herpes simplex virus (HSV) infections. In adults, valacyclovir
has replaced oral acyclovir in many clinical scenarios. Pharmacokinetic data
support the use of oral valacyclovir in children, but practical problems with
the adult tablets exist in children. For children, a formulation with
acceptable palatability, good pharmaceutical quality, and possibility of
flexible dosing is needed. This study is part of the VALID-project in which a
new paediatric formulation of valacyclovir will be developed and evaluated.
During the development phase palatability testing will be performed. The
bioequivalence of the new paediatric formulation versus valacyclovir tablets
will be investigated in a study in healthy adults. Subsequently the
pharmacokinetics and safety of the new paediatric oral formulation will be
determined in children receiving this drug as prophylaxis against VZV and HSV
infections post stem cell transplantation. The VALID-project has been granted
by ZonMW within the *Priority Medicines for Children* Programme.
Study objective
Primary
To determine whether the palatability of a newly developed formulation of
valacyclovir is non-inferior to administration of crushed and suspended tablets
in children, is the primary objective of the second phase of the trial.
The primary objective of the first phase of the trial was to determine which of
three newly developed formulations of valacyclovir is accepted best in children.
Secondary
To determine whether parents can predict the palatability preference of their
child.
In the second phase of the trial a new secondary objective is to validate the
results of the in vitro taste assessment.
Study design
Randomized, two-period, multi centre, cross-over study
Intervention
Three formulations will be tested. Each participant will taste 4 or 8 ml of
each formulation containing 20-25 mg/ml valacyclovir.
Collection of 2 ml of saliva (voluntary) for research on genetics of taste.
Study burden and risks
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 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.
The taste assessment will be performed directly after a regular visit to the
outpatient clinic. Subjects don*t have to come to the hospital separately to
participate in this study.
Adverse events of prolonged use of valacyclovir include: headache (>=10%),
nausea, vomiting, diarrhea, dizziness, rash, pruritis, photosensibilisation
(>=1% and <10%), leucopenia, thrombocytopenia, hallucinations, mental confusion,
diminished consciousness, agitation, tremor, dyspnoea, abdominal discomfort,
urticaria, kidney pain (>=0.1% and <1%), anaphylaxis, ataxia, dysarthria,
convulsions, encephalopathy, coma, psychotic symptoms, reversible increase in
liver enzymes and bilirubin, angioedema, impaired renal function and acute
renal failure (>=0.01% and <0.1%).
During the taste assessment, subjects will receive a dose of valacyclovir that
is equal to a single therapeutic dose, or less, depending on body weight (see
6.3). It is not expected that drug resistance to valacyclovir or acyclovir will
develop.
The excipients that are used in the formulations, are commonly used in
extemporaneously prepared products by pharmacists.
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1. Subject is at least 4 years of age.
2. Subject is capable of performing the taste assessment, according to the investigator*s judgement.
3. The child is willing to participate in the taste assessment.
4. Signed informed consent by the legal guardian for participation of the child and if the parent also wants to participate: signed informed consent for their own participation, prior to start of the study.
Exclusion criteria
1. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients (as used in the study formulation). An exception is a sensitivity reaction on asparaginase, since this is a common reaction in children, and no cross sensitivity with other medicinal products has been demonstrated.
2. Presence of any condition that influences taste sensation (such as upper respiratory infection, febrile illness within 3 days before the first dose, mucositis or use of medication (not included in standard protocol for treatment of underlying disease) that influences taste perception, as described in the label information).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-000577-22-NL |
| ClinicalTrials.gov | NCT01682109 |
| CCMO | NL39424.000.12 |