Pharmacokinetics of a new paediatric formulation of valacyclovir used for prophylaxis and treatment of VZV and HSV infections in children (VALID II).

Herpes infections in immunocompromised patient cause longer periods of clinical
symptoms and viral shedding, increased
severity and more frequent episodes of reactivation. This may leed to
dissemination, hepatitis, post herpetic neuralgia,
bacterial super infection, pneumonitis, encephalitis and death.
Valacyclovir is an oral prodrug of acyclovir, with at least equal efficacy and
a similar safety profile as intravenous aciclovir
and therefore less expensive and more convenient. However, in immunocompromised
children practical problems exist
with adult-dose tablets. A formulation with acceptable palatability, good
pharmaceutical quality and possibility of flexible
dosing is needed. A new paediatric formulation (oral solution) has been
developed to fullfill those needs. The pharmacokinetics of this formulation
will be investigated in children who have an indication for (val)Acyclovir
prophylaxis.

In this trial the plasma pharmacokinetics of acyclovir will be investigated
after administration of valacyclovir oral solution in children who have an
indication for (val)Acyclovir prophylactic treatment.
Furhermore, the safety profile of a single dose of valacyclovir oral solution
in children will be determined.

This study will be an opportunistic design, single dose (at steady state),
one-period, steady state, multiple center, trial.

Pharmacokinetics will be determined on a day of valacyclovir oral solution
dosing (which is giving as standard of care).

Intake of valacyclovir oral solution (as standard of care) and collection of
bloodsamples for determination of the pharmacokinetics.

This study will be performed in children who have an indication for
(val)Acyclovir prophylactic treatment. These children are admitted to the
hospital. Therefore, no more visits are scheduled for the study. The duration
of the entire trial is one day during hospital admission.
One could argue that a study in children might be unethical, but the oral
solution had antiviral activity. So, the study participants will benefit from
the participation in this clinical trial. The study participants are subjects
between 2 and 12 years, these subjects are representative for the group who
will receive this formulation.
On the other hand, valacyclovir can lead to adverse events including: headache
(*10%), nausea, vomiting, diarrhea, dizziness, rash, pruritis (*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%).
Adverse events of acyclovir are comparable, but also include: shortness of
breath (*0,01% and <0,1%) anaemia and hepatitis (*0,01%).
However, the patients will receive valayclovir anyway according to the local
protocol. So, the study does not rise or decrease the risk on these adverse
events. For pharmacokinetic purposes 7 blood samples will be taken in total.
The total blood volume collected will be approximately 21 mL.
Blood samples will be collected from an inserted canulla or PAC being already
in place for treatment of their underlying condition, which minimizes
inconvenience for the children. The overall risk is judged to be minimal.