Clinical trial NCT01689285: Bioequivalence Study in Healthy Volunteers of a New Paediatric Formulation of Valacyclovir
Official title: Bioequivalence Study in Healthy Volunteers of a New Paediatric Formulation of Valacyclovir Used for Prophylaxis and Treatment of VZV and HSV Infections in Children, Phase I (VALID-I)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Varicella Zoster Virus Infection
Herpes Simplex Virus Infection
Keywords: bioequivalence
pharmacokinetics
valacyclovir
paediatric formulation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2012-09-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: A new paediatric formulation (oral liquid) has been developed for flexible and accurate dosing of valacyclovir in children. To establish the bioavailability of this new formulation, healthy volunteers will be exposed to the new formulation and to valacyclovir tablets. The concentration of valacyclovir in their blood after exposure to the oral liquid will be measured and compared to the tablet.

Detailed description: Bioequivalence of the new valcyclovir formulation will be tested according to the EMA guideline for bioequivalence.

Eligibility criteria: Inclusion Criteria:

* Subject is at least 18 and not older than 55 years of age at screening.
* 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
* Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
* Subject has signed the Informed Consent Form prior to screening evaluations.
* 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 recorded.
* Subject has a normal blood pressure and pulse rate, according to the investigator's judgement.
* 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:

* Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
* Positive HIV, hepatitis B or C test.
* Therapy with any drug (for two weeks preceding dosing), except for acetaminophen.
* Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
* Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
* History of or current abuse of drugs, alcohol or solvents.
* Inability to understand the nature and extent of the trial and the procedures required.
* Participation in a drug trial within 60 days prior to the first dose.
* Donation of blood within 60 days prior to the first dose.
* Febrile illness within 3 days before the first dose.
* Pregnant female (as confirmed by an HCG test performed less than 4 weeks before the first dose) or breast-feeding female.

Primary outcomes:
measure: Geometric Mean Ratios and 90% confidence intervals of pharmacokinetic parameters of acyclovir taken as valacyclovir tablet or oral solution
timeFrame: up to 8 days
Secondary outcomes:
measure: Determine the safety profile of a single dose of valacyclovir oral solution
timeFrame: day 1 and 8
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: Radboud University Medical Center
name: Bas Schouwenberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bastiaans DE, Bartels-Wilmer CM, Colbers AP, Heijens CA, Velthoven-Graafland K, Smeets OS, Vink N, Harbers VE, Warris A, Burger DM. A new paediatric formulation of valaciclovir: development and bioequivalence assessment. Arch Dis Child. 2016 Oct;101(10):971-2. doi: 10.1136/archdischild-2015-310266. Epub 2016 May 9. No abstract available.