<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01689285</url>
  </required_header>
  <id_info>
    <org_study_id>UMCN-AKF 11.04</org_study_id>
    <nct_id>NCT01689285</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study in Healthy Volunteers of a New Paediatric Formulation of Valacyclovir</brief_title>
  <acronym>VALID-I</acronym>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A new paediatric formulation (oral liquid) has been developed for flexible and accurate&#xD;
      dosing of valacyclovir in children. To establish the bioavailability of this new formulation,&#xD;
      healthy volunteers will be exposed to the new formulation and to valacyclovir tablets. The&#xD;
      concentration of valacyclovir in their blood after exposure to the oral liquid will be&#xD;
      measured and compared to the tablet.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Bioequivalence of the new valcyclovir formulation will be tested according to the EMA&#xD;
      guideline for bioequivalence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2013</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric Mean Ratios and 90% confidence intervals of pharmacokinetic parameters of acyclovir taken as valacyclovir tablet or oral solution</measure>
    <time_frame>up to 8 days</time_frame>
    <description>bioequivalence will be determined by comparing AUC0-inf, Cmax and tmax of both formulations in healthy adult volunteers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine the safety profile of a single dose of valacyclovir oral solution</measure>
    <time_frame>day 1 and 8</time_frame>
    <description>healthy volunteers will be interviewed for adverse events, laboratory safety assessments will be performed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Varicella Zoster Virus Infection</condition>
  <condition>Herpes Simplex Virus Infection</condition>
  <arm_group>
    <arm_group_label>valacyclovir tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of 500 mg once daily on day 1 (group A) or on day 8 (group B)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>valacyclovir oral solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of 500 mg once daily on day 1 (group B) or on day 8 (group A)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>valacyclovir tablet</intervention_name>
    <description>16 healthy adult volunteers (18-55 yr) will be exposed to one tablet</description>
    <arm_group_label>valacyclovir tablet</arm_group_label>
    <other_name>Zelitrex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>valacyclovir oral solution</intervention_name>
    <description>16 healthy adult volunteers (18-55 yr) will be exposed to 10 ml once</description>
    <arm_group_label>valacyclovir oral solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is at least 18 and not older than 55 years of age at screening.&#xD;
&#xD;
          -  Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at&#xD;
             least 3 months prior to the first dosing&#xD;
&#xD;
          -  Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.&#xD;
&#xD;
          -  Subject has signed the Informed Consent Form prior to screening evaluations.&#xD;
&#xD;
          -  Subject is in good age-appropriate health condition as established by medical history,&#xD;
             physical examination, electrocardiography, results of biochemistry, haematology and&#xD;
             urinalysis testing within 4 weeks prior to the first dose. Results of biochemistry,&#xD;
             haematology and urinalysis testing should be within the laboratory's reference ranges&#xD;
             (see Appendix A). If laboratory results are not within the reference ranges, the&#xD;
             subject is included on condition that the investigator judges that the deviations are&#xD;
             not clinically relevant. This should be clearly recorded.&#xD;
&#xD;
          -  Subject has a normal blood pressure and pulse rate, according to the investigator's&#xD;
             judgement.&#xD;
&#xD;
          -  Female subject is either not of childbearing potential, defined as postmenopausal for&#xD;
             at least 1 year or is of childbearing potential with adequate contraception (e.g.&#xD;
             hysterectomy, bilateral tubal ligation, (nonhormonal) intrauterine device, total&#xD;
             abstinence, double barrier methods, vasectomized partner).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.&#xD;
&#xD;
          -  Positive HIV, hepatitis B or C test.&#xD;
&#xD;
          -  Therapy with any drug (for two weeks preceding dosing), except for acetaminophen.&#xD;
&#xD;
          -  Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular&#xD;
             disorders, neurological disorders (especially seizures and migraine),&#xD;
             gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders&#xD;
             (especially diabetes mellitus), coagulation disorders.&#xD;
&#xD;
          -  Relevant history or current condition that might interfere with drug absorption,&#xD;
             distribution, metabolism or excretion.&#xD;
&#xD;
          -  History of or current abuse of drugs, alcohol or solvents.&#xD;
&#xD;
          -  Inability to understand the nature and extent of the trial and the procedures&#xD;
             required.&#xD;
&#xD;
          -  Participation in a drug trial within 60 days prior to the first dose.&#xD;
&#xD;
          -  Donation of blood within 60 days prior to the first dose.&#xD;
&#xD;
          -  Febrile illness within 3 days before the first dose.&#xD;
&#xD;
          -  Pregnant female (as confirmed by an HCG test performed less than 4 weeks before the&#xD;
             first dose) or breast-feeding female.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bas Schouwenberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radboud University Medical Center</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <results_reference>
    <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.</citation>
    <PMID>27162003</PMID>
  </results_reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>December 4, 2020</last_update_submitted>
  <last_update_submitted_qc>December 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bioequivalence</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>valacyclovir</keyword>
  <keyword>paediatric formulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Herpes Simplex</mesh_term>
    <mesh_term>Herpes Zoster</mesh_term>
    <mesh_term>Varicella Zoster Virus Infection</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valacyclovir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01689285
org study id: UMCN-AKF 11.04
nct id: NCT01689285
lead sponsor: 
has dmc: No
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.
Bioequivalence of the new valcyclovir formulation will be tested according to the EMA
      guideline for bioequivalence.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Geometric Mean Ratios and 90% confidence intervals of pharmacokinetic parameters of acyclovir taken as valacyclovir tablet or oral solution
time frame: up to 8 days
description: bioequivalence will be determined by comparing AUC0-inf, Cmax and tmax of both formulations in healthy adult volunteers.
measure: Determine the safety profile of a single dose of valacyclovir oral solution
time frame: day 1 and 8
description: healthy volunteers will be interviewed for adverse events, laboratory safety assessments will be performed.
arm group label: valacyclovir tablet
arm group type: Active Comparator
description: Administration of 500 mg once daily on day 1 (group A) or on day 8 (group B)
arm group label: valacyclovir oral solution
arm group type: Experimental
description: Administration of 500 mg once daily on day 1 (group B) or on day 8 (group A)
intervention type: Drug
intervention name: valacyclovir tablet
description: 16 healthy adult volunteers (18-55 yr) will be exposed to one tablet
arm group label: valacyclovir tablet
other name: Zelitrex
intervention type: Drug
intervention name: valacyclovir oral solution
description: 16 healthy adult volunteers (18-55 yr) will be exposed to 10 ml once
arm group label: valacyclovir oral solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bas Schouwenberg, MD
role: Principal Investigator
affiliation: Radboud University Medical Center
facility: 
country: Netherlands
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.
PMID: 27162003
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Virus Diseases
mesh term: Herpes Simplex
mesh term: Herpes Zoster
mesh term: Varicella Zoster Virus Infection
mesh term: Valacyclovir