Bioequivalence Study in Healthy Volunteers of a New Paediatric Formulation of Valacyclovir (VALID-I)

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)

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.

Study Overview

• Status: Completed
• Conditions: Varicella Zoster Virus Infection; Herpes Simplex Virus Infection
• Intervention / Treatment: Drug: valacyclovir tablet; Drug: valacyclovir oral solution

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: valacyclovir tablet; Administration of 500 mg once daily on day 1 (group A) or on day 8 (group B)	Drug: valacyclovir tablet; 16 healthy adult volunteers (18-55 yr) will be exposed to one tablet; Other Names: Zelitrex
Experimental: valacyclovir oral solution; Administration of 500 mg once daily on day 1 (group B) or on day 8 (group A)	Drug: valacyclovir oral solution; 16 healthy adult volunteers (18-55 yr) will be exposed to 10 ml once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratios and 90% confidence intervals of pharmacokinetic parameters of acyclovir taken as valacyclovir tablet or oral solution	bioequivalence will be determined by comparing AUC0-inf, Cmax and tmax of both formulations in healthy adult volunteers.	up to 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the safety profile of a single dose of valacyclovir oral solution	healthy volunteers will be interviewed for adverse events, laboratory safety assessments will be performed.	day 1 and 8

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Bas Schouwenberg, MD, Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: September 17, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioequivalence; valacyclovir; paediatric formulation
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease Attributes; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Infections; Communicable Diseases; Virus Diseases; Herpes Zoster; Herpes Simplex; Varicella Zoster Virus Infection; Anti-Infective Agents; Antiviral Agents; Valacyclovir
• Other Study ID Numbers: UMCN-AKF 11.04