In this trial will be investigated if a new formulation of valacyclovir, e.g. oral solution, is bioequivalent to valacyclovir tablets. This comparison will be made by determining pharmacokinetic parameters (AUC0-*, Cmax, and tmax) of both…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic parameters of valacyclovir
Secondary outcome
amount and severity of adverse events
Background summary
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. To ensure comparable in vivo efficacy, the bioequivalence of this
formulation versus valacyclovir tablets will be investigated in healthy adults,
according to the EMA guidelines for bioequivalence.
Study objective
In this trial will be investigated if a new formulation of valacyclovir, e.g.
oral solution, is bioequivalent to valacyclovir tablets. This comparison will
be made by determining pharmacokinetic parameters (AUC0-*, Cmax, and tmax) of
both formulations in healthy adult volunteers.
Next to this, the safety profile of a single dose of valacyclovir oral solution
will be determined by monitoring adverse events.
Study design
Open label, two-period, single dose, crossover, single centre, randomized
phase-I trial.
Group A will receive a single dose of valacyclovir tablet 500 mg (Zelitrex®) on
day 1. After a wash-out period of 7 days, the subjects will receive a single
dose of valacyclovir oral solution (20 mg/mL) equal to valacyclovir 500 mg (25
mL) on day 8.
Group B will receive a single dose of valacyclovir oral solution (20 mg/mL)
equal to valacyclovir 500 mg (25 mL). After a wash-out period of 7 days, the
subjects will receive a single dose of valacyclovir tablet 500 mg (Zelitrex®)
on day 8.
Subjects will be randomly divided into two treatment groups.
Intervention
Administration of a single dose of valacyclovir 500 mg on two days.
Study burden and risks
The subjects are healthy volunteers. This treatment will not be of benefit to
their health. The subject need to be present at the trial location during 2
days. The trial period (excluding screening) encompasses 8 days. The cannula
used to draw blood may cause inconvenience or pain at the insertion site. Blood
will be drawn through a venous punction (at screening) and through the cannula
(on trial days).
In this trial a low dose of valayclovir is used and therefore the risk on
adverse events is minimized, but not excluded. Possible side effects of
valacyclovir include 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%).
The single-dose nature of this trial minimizes the development of drug
resistance.
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 18 and not older than 55 years of age at screening.
2. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing
3. Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
4. Subject has signed the Informed Consent Form prior to screening evaluations.
5. Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to the first dose. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included on condition that the investigator judges that the deviations are not clinically relevant. This should be clearly re-corded.
6. Subject has a normal blood pressure and pulse rate, according to the investigator's judgement.
7. Female subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or is of childbearing potential with adequate contraception (e.g. hysterectomy, bilateral tubal ligation, (nonhormonal) intrauterine device, total abstinence, double barrier methods, vasectomized partner).
Exclusion criteria
1. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
2. Positive HIV, hepatitis B or C test.
3. Therapy with any drug (for two weeks preceding dosing), except for acetaminophen.
4. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disor-ders, neurological disorders (especially seizures and migraine), gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
5. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
6. History of or current abuse of drugs, alcohol or solvents.
7. Inability to understand the nature and extent of the trial and the procedures required.
8. Participation in a drug trial within 60 days prior to the first dose.
9. Donation of blood within 60 days prior to the first dose.
10. Febrile illness within 3 days before the first dose.
11. Pregnant female (as confirmed by an HCG test performed less than 4 weeks before the first dose) or breast-feeding female.
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 | EUCTR2011-005077-22-NL |
| CCMO | NL39308.091.12 |