<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/NCT03813030</url>
  </required_header>
  <id_info>
    <org_study_id>FDA02_AIM4</org_study_id>
    <secondary_id>2018-002507-33</secondary_id>
    <nct_id>NCT03813030</nct_id>
  </id_info>
  <brief_title>An Exploratory Study in Healthy Volunteers to Investigate the Cross-talk Between Local Drug Concentrations in the Skin and Systemic Concentrations During Topical Bioequivalence Studies Using Dermal Sampling Techniques</brief_title>
  <official_title>An Exploratory Study in Healthy Volunteers to Investigate the Cross-talk Between Local Drug Concentrations in the Skin and Systemic Concentrations During Topical Bioequivalence Studies Using Dermal Sampling Techniques</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joanneum Research Forschungsgesellschaft mbH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Joanneum Research Forschungsgesellschaft mbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a single center, open label, exploratory research study to assess the dermal and&#xD;
      systemic PK of marketed products of lidocaine/prilocaine in 26 healthy participants using&#xD;
      dermal open flow microperfusion (dOFM) and microdialysis (MD) for dermal sampling.&#xD;
&#xD;
      The clinical study aims to identify potential cross-talk between the extracellular&#xD;
      compartments of viable skin and blood circulation during (bioequivalence) BE assessments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The clinical study is divided into a pilot and a pivotal study.&#xD;
&#xD;
      The pilot study will involve 6 healthy adult participants and in each participant the&#xD;
      concentration of lidocaine/prilocaine will be assessed in the dermis and in the systemic&#xD;
      circulation after topical application of lidocaine/prilocaine (dermal sampling visit). The&#xD;
      pilot study aims to develop the optimal study design for the pivotal study. Thereby the&#xD;
      effect of and removal of the topical dose will be tested as well as if this topical dose&#xD;
      establishes well quantifiable systemic drug levels that allow an investigation of the&#xD;
      cross-talk between skin and systemic circulation within the pivotal study. Further the&#xD;
      feasibility of dermal microdialysis (dMD) will be tested and compared with dOFM.&#xD;
&#xD;
      The pivotal study will involve 20 healthy adult participants. It aims to investigate a&#xD;
      potential cross-talk between skin and systemic circulation by comparing dermal&#xD;
      lidocaine/prilocaine concentrations (assessed with dOFM and MD) and blood&#xD;
      lidocaine/prilocaine concentrations in a dermal sampling visit. Furthermore, the systemic&#xD;
      clearance of lidocaine will be investigated in each of the 20 participants in a separate&#xD;
      clearance visit after intravenous infusion of lidocaine.&#xD;
&#xD;
      In the dermal sampling visits dOFM and microdialysis probes will be inserted into the dermis&#xD;
      to monitor the dermal drug concentration up to 12 h post-dose in topically treated as well as&#xD;
      untreated skin sites. Blood samples will be drawn to assess the systemic drug levels. All&#xD;
      samples will be assayed for lidocaine and prilocaine concentrations. The blood samples in the&#xD;
      clearance visit will be assayed for lidocaine only.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Actual">August 28, 2019</completion_date>
  <primary_completion_date type="Actual">August 28, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Pilot Study with 6 participants and pivotal study with 20 participants</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the dermal concentration versus time curve for lidocaine (pilot study: 6 participants, pivotal study: 20 participants)</measure>
    <time_frame>13 hours</time_frame>
    <description>Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the area under the dermal concentration versus time curve AUC (ng*h/mL).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the dermal concentration time curve for prilocaine (pilot study: 6 participants, pivotal study: 20 participants)</measure>
    <time_frame>13 hours</time_frame>
    <description>Dermal concentrations (ng/mL) of prilocaine will be measured to calculate the dermal area under the dermal concentration versus time curve AUC (ng*h/mL).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximal dermal concentration of lidocaine (pilot study: 6 participants, pivotal study: 20 participants)</measure>
    <time_frame>13 hours</time_frame>
    <description>Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the maximal dermal concentration (ng/mL).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximal dermal concentration of prilocaine (pilot study: 6 participants, pivotal study: 20 participants)</measure>
    <time_frame>13 hours</time_frame>
    <description>Dermal concentrations (ng/mL) of prilocaine will be measured to calculate the maximal dermal concentration (ng/mL).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood lidocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)</measure>
    <time_frame>13 hours</time_frame>
    <description>Lidocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood prilocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)</measure>
    <time_frame>13 hours</time_frame>
    <description>Prilocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lidocaine clearance (Pivotal study) - 20 participants</measure>
    <time_frame>6 hours post dosing</time_frame>
    <description>Blood concentration (ng/mL) of lidocaine will be measured to obtain the concentration-time curves and to calculated the individual lidocaine clearance (L/min).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Healthy</condition>
  <condition>Dermal Pharmacokinetic Measurement</condition>
  <arm_group>
    <arm_group_label>Pilot Study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dermal-sampling visit: Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of lidocaine/ prilocaine using dermal open flow microperfusion (dOFM) and dermal microdialysis (dMD) after topical application of Lidocaine 2.5% and Prilocaine 2.5% cream in 6 participants. Additionally systemic appearance of lidocaine/prilocaine is measured by blood sampling.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pivotal Study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dermal-sampling visit: Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of lidocaine/ prilocaine using dermal open flow microperfusion (dOFM) and dermal microdialysis (dMD) after topical application of Lidocaine 2.5% and Prilocaine 2.5% cream in 20 participants. Additionally systemic appearance of lidocaine/prilocaine is measured by blood sampling.&#xD;
Clearance Visit: Clearance of lidocaine will be evaluated after intravenous infusion of lidocaine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intravenous infusion of lidocaine</intervention_name>
    <description>Lidocaine is intravenously administered in clearance visit and blood samples are taken to calculate individual clearance of each participant.</description>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine 2.5% and Prilocaine 2.5% cream&quot;, USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA)</intervention_name>
    <description>Topical application in dermal-sampling visit</description>
    <arm_group_label>Pilot Study</arm_group_label>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocorit 2%-Ampullen&quot; (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria)</intervention_name>
    <description>Intravenous infusion in clearance visit</description>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dermal open flow microperfusion</intervention_name>
    <description>Dermal open flow microperfusion will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentration in the dermis.&#xD;
Interstitial fluid (ISF) sampling: 1 hour pre-dose and 12 hours post-dose</description>
    <arm_group_label>Pilot Study</arm_group_label>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dermal Microdialysis</intervention_name>
    <description>Dermal microdialysis will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentrations in the dermis.&#xD;
Interstitial fluid (ISF) sampling: 1 hour pre-dose and 12 hours post-dose</description>
    <arm_group_label>Pilot Study</arm_group_label>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sampling in dermal sampling visit</intervention_name>
    <description>1 sample is taken pre-dose and 12 samples are taken post-dose.</description>
    <arm_group_label>Pilot Study</arm_group_label>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sampling in clearance visit</intervention_name>
    <description>1 sample is taken pre-dose, 3 samples during intravenous infusion and 13 samples post-dose.</description>
    <arm_group_label>Pivotal Study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy, adult volunteers of age 18 to 65 years (both inclusive).&#xD;
&#xD;
          2. Males or non-pregnant, non-breast feeding females using adequate contraceptive methods&#xD;
             or abstinence.&#xD;
&#xD;
          3. Able to read, understand and sign the written informed consent form.&#xD;
&#xD;
          4. Willing to follow the protocol requirements and comply with protocol restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Social Habits&#xD;
&#xD;
               1. Smoker who is not willing to restrain from smoking during the in-house visits.&#xD;
&#xD;
               2. History of drug and/or alcohol abuse within one year of start of study as judged&#xD;
                  by the investigator.&#xD;
&#xD;
          2. Medications&#xD;
&#xD;
               1. Current treatment with systemically effective corticosteroids, monoamine oxidase&#xD;
                  (MAO) inhibitors, systemic non-selective beta-blockers, warfarin or&#xD;
                  anticholinergic drugs, or use of any medications referred in the prescription&#xD;
                  information of the products.&#xD;
&#xD;
               2. Hormonal contraceptive or hormone replacement therapy, routine vitamins or other&#xD;
                  prescribed medication are allowed if dose is stable.&#xD;
&#xD;
          3. Diseases&#xD;
&#xD;
               1. Congenital or idiopathic methemoglobinemia.&#xD;
&#xD;
               2. History of deep vein thrombosis (DVT)/pulmonary emboly (PE)&#xD;
&#xD;
               3. Inherited blood disorders (such as factor V Leiden) who are prone to&#xD;
                  hypercoagulable state&#xD;
&#xD;
               4. Glucose-6-phosphate dehydrogenase deficiencies&#xD;
&#xD;
               5. Presence of any acute or chronic diseases or malignancies unless deemed not&#xD;
                  clinically significant by the investigator.&#xD;
&#xD;
          4. Any reason, which in the opinion of the investigator, would prevent the subject from&#xD;
             safely participating in the study.&#xD;
&#xD;
          5. Any abnormalities found at physical examination or vital signs, unless deemed not&#xD;
             clinically significant by the investigator.&#xD;
&#xD;
          6. Clinically significant abnormal laboratory evaluation results, as deemed by the&#xD;
             investigator.&#xD;
&#xD;
          7. Clinically significant abnormal 12-lead ECG at screening, as deemed by the&#xD;
             investigator.&#xD;
&#xD;
          8. Positive results to the test for hepatitis B antigen or hepatitis C antibodies.&#xD;
&#xD;
          9. Positive HIV test.&#xD;
&#xD;
         10. Positive alcohol breath test.&#xD;
&#xD;
         11. Blood donation within 30 days or significant loss of blood or plasma (more than 550&#xD;
             ml) within 90 days prior to screening.&#xD;
&#xD;
         12. Subject who have received an investigational drug within 30 days prior to the initial&#xD;
             dose of study medication.&#xD;
&#xD;
         13. Known or suspected allergy/hypersensitivity to lidocaine or prilocaine, known history&#xD;
             of sensitivity to local anesthetics of the amide type or to any other component of the&#xD;
             product, other related products, or any inactive ingredients.&#xD;
&#xD;
         14. Tattoos or broken and/or damaged skin at the application areas.&#xD;
&#xD;
         15. Active skin diseases like psoriasis or atopic dermatitis, as judged by the&#xD;
             investigator.&#xD;
&#xD;
         16. Scarring at the anterior part of the thighs.&#xD;
&#xD;
         17. Subjects prone to keloid or hypertrophic scar formation or any known wound healing&#xD;
             disorder.&#xD;
&#xD;
         18. Recent and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of&#xD;
             fainting, palpitations, etc.), as judged by the investigator.&#xD;
&#xD;
         19. Not willing to avoid excessive sun exposure, steam baths, sauna, swimming and other&#xD;
             strenuous activities for 14 days after Visit 2 to ensure good tissue regeneration.&#xD;
&#xD;
         20. Not willing to refrain from shaving the planned application sites or using skin care&#xD;
             products on the planned application sites for at least 5 days prior to start of Visit&#xD;
             2.&#xD;
&#xD;
         21. Pronounced hairiness on the planned application sites that may negatively affect BE&#xD;
             testing.&#xD;
&#xD;
         22. Known allergy/hypersensitivity to any of the materials/supplies used during the study.&#xD;
&#xD;
         23. Presence of needle phobia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Pieber, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Graz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Research Center, Medical University Graz</name>
      <address>
        <city>Graz</city>
        <zip>8010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <citation>Bodenlenz M, Tiffner KI, Raml R, Augustin T, Dragatin C, Birngruber T, Schimek D, Schwagerle G, Pieber TR, Raney SG, Kanfer I, Sinner F. Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to Evaluate Topical Bioequivalence. Clin Pharmacokinet. 2017 Jan;56(1):91-98. doi: 10.1007/s40262-016-0442-z. Erratum In: Clin Pharmacokinet. 2017 Jan;56(1):99.</citation>
    <PMID>27539717</PMID>
  </reference>
  <reference>
    <citation>Bodenlenz M, Dragatin C, Liebenberger L, Tschapeller B, Boulgaropoulos B, Augustin T, Raml R, Gatschelhofer C, Wagner N, Benkali K, Rony F, Pieber T, Sinner F. Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution. Pharm Res. 2016 Sep;33(9):2229-38. doi: 10.1007/s11095-016-1960-y. Epub 2016 Jun 6.</citation>
    <PMID>27271272</PMID>
  </reference>
  <reference>
    <citation>Rowland M, Thomson PD, Guichard A, Melmon KL. Disposition kinetics of lidocaine in normal subjects. Ann N Y Acad Sci. 1971 Jul 6;179:383-98. doi: 10.1111/j.1749-6632.1971.tb46915.x. No abstract available.</citation>
    <PMID>5285383</PMID>
  </reference>
  <reference>
    <citation>Benfeldt E, Hansen SH, Volund A, Menne T, Shah VP. Bioequivalence of topical formulations in humans: evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method. J Invest Dermatol. 2007 Jan;127(1):170-8. doi: 10.1038/sj.jid.5700495. Epub 2006 Jul 27.</citation>
    <PMID>16874309</PMID>
  </reference>
  <reference>
    <citation>Estebe JP. Intravenous lidocaine. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):513-521. doi: 10.1016/j.bpa.2017.05.005. Epub 2017 May 30.</citation>
    <PMID>29739540</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dermal open flow microperfusion</keyword>
  <keyword>Dermal microdialysis</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Prilocaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03813030
org study id: FDA02_AIM4
secondary id: 2018-002507-33
nct id: NCT03813030
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
This will be a single center, open label, exploratory research study to assess the dermal and
      systemic PK of marketed products of lidocaine/prilocaine in 26 healthy participants using
      dermal open flow microperfusion (dOFM) and microdialysis (MD) for dermal sampling.

      The clinical study aims to identify potential cross-talk between the extracellular
      compartments of viable skin and blood circulation during (bioequivalence) BE assessments.
The clinical study is divided into a pilot and a pivotal study.

      The pilot study will involve 6 healthy adult participants and in each participant the
      concentration of lidocaine/prilocaine will be assessed in the dermis and in the systemic
      circulation after topical application of lidocaine/prilocaine (dermal sampling visit). The
      pilot study aims to develop the optimal study design for the pivotal study. Thereby the
      effect of and removal of the topical dose will be tested as well as if this topical dose
      establishes well quantifiable systemic drug levels that allow an investigation of the
      cross-talk between skin and systemic circulation within the pivotal study. Further the
      feasibility of dermal microdialysis (dMD) will be tested and compared with dOFM.

      The pivotal study will involve 20 healthy adult participants. It aims to investigate a
      potential cross-talk between skin and systemic circulation by comparing dermal
      lidocaine/prilocaine concentrations (assessed with dOFM and MD) and blood
      lidocaine/prilocaine concentrations in a dermal sampling visit. Furthermore, the systemic
      clearance of lidocaine will be investigated in each of the 20 participants in a separate
      clearance visit after intravenous infusion of lidocaine.

      In the dermal sampling visits dOFM and microdialysis probes will be inserted into the dermis
      to monitor the dermal drug concentration up to 12 h post-dose in topically treated as well as
      untreated skin sites. Blood samples will be drawn to assess the systemic drug levels. All
      samples will be assayed for lidocaine and prilocaine concentrations. The blood samples in the
      clearance visit will be assayed for lidocaine only.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Pilot Study with 6 participants and pivotal study with 20 participants
primary purpose: Other
masking: None (Open Label)
measure: Area under the dermal concentration versus time curve for lidocaine (pilot study: 6 participants, pivotal study: 20 participants)
time frame: 13 hours
description: Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the area under the dermal concentration versus time curve AUC (ng*h/mL).
measure: Area under the dermal concentration time curve for prilocaine (pilot study: 6 participants, pivotal study: 20 participants)
time frame: 13 hours
description: Dermal concentrations (ng/mL) of prilocaine will be measured to calculate the dermal area under the dermal concentration versus time curve AUC (ng*h/mL).
measure: Maximal dermal concentration of lidocaine (pilot study: 6 participants, pivotal study: 20 participants)
time frame: 13 hours
description: Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the maximal dermal concentration (ng/mL).
measure: Maximal dermal concentration of prilocaine (pilot study: 6 participants, pivotal study: 20 participants)
time frame: 13 hours
description: Dermal concentrations (ng/mL) of prilocaine will be measured to calculate the maximal dermal concentration (ng/mL).
measure: Blood lidocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)
time frame: 13 hours
description: Lidocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.
measure: Blood prilocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)
time frame: 13 hours
description: Prilocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.
measure: Lidocaine clearance (Pivotal study) - 20 participants
time frame: 6 hours post dosing
description: Blood concentration (ng/mL) of lidocaine will be measured to obtain the concentration-time curves and to calculated the individual lidocaine clearance (L/min).
arm group label: Pilot Study
arm group type: Experimental
description: Dermal-sampling visit: Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of lidocaine/ prilocaine using dermal open flow microperfusion (dOFM) and dermal microdialysis (dMD) after topical application of Lidocaine 2.5% and Prilocaine 2.5% cream in 6 participants. Additionally systemic appearance of lidocaine/prilocaine is measured by blood sampling.
arm group label: Pivotal Study
arm group type: Experimental
description: Dermal-sampling visit: Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of lidocaine/ prilocaine using dermal open flow microperfusion (dOFM) and dermal microdialysis (dMD) after topical application of Lidocaine 2.5% and Prilocaine 2.5% cream in 20 participants. Additionally systemic appearance of lidocaine/prilocaine is measured by blood sampling.
Clearance Visit: Clearance of lidocaine will be evaluated after intravenous infusion of lidocaine.
intervention type: Procedure
intervention name: Intravenous infusion of lidocaine
description: Lidocaine is intravenously administered in clearance visit and blood samples are taken to calculate individual clearance of each participant.
arm group label: Pivotal Study
intervention type: Drug
intervention name: Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA)
description: Topical application in dermal-sampling visit
arm group label: Pilot Study
arm group label: Pivotal Study
intervention type: Drug
intervention name: Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria)
description: Intravenous infusion in clearance visit
arm group label: Pivotal Study
intervention type: Device
intervention name: Dermal open flow microperfusion
description: Dermal open flow microperfusion will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentration in the dermis.
Interstitial fluid (ISF) sampling: 1 hour pre-dose and 12 hours post-dose
arm group label: Pilot Study
arm group label: Pivotal Study
intervention type: Device
intervention name: Dermal Microdialysis
description: Dermal microdialysis will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentrations in the dermis.
Interstitial fluid (ISF) sampling: 1 hour pre-dose and 12 hours post-dose
arm group label: Pilot Study
arm group label: Pivotal Study
intervention type: Procedure
intervention name: Blood sampling in dermal sampling visit
description: 1 sample is taken pre-dose and 12 samples are taken post-dose.
arm group label: Pilot Study
arm group label: Pivotal Study
intervention type: Procedure
intervention name: Blood sampling in clearance visit
description: 1 sample is taken pre-dose, 3 samples during intravenous infusion and 13 samples post-dose.
arm group label: Pivotal Study
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Thomas Pieber, Prof.
role: Principal Investigator
affiliation: Medical University of Graz
facility: 
country: Austria
citation: Bodenlenz M, Tiffner KI, Raml R, Augustin T, Dragatin C, Birngruber T, Schimek D, Schwagerle G, Pieber TR, Raney SG, Kanfer I, Sinner F. Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to Evaluate Topical Bioequivalence. Clin Pharmacokinet. 2017 Jan;56(1):91-98. doi: 10.1007/s40262-016-0442-z. Erratum In: Clin Pharmacokinet. 2017 Jan;56(1):99.
PMID: 27539717
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responsible party type: Sponsor
mesh term: Lidocaine
mesh term: Prilocaine
sharing ipd: No