An Exploratory Pilot Study in Healthy Volunteers to Assess the Parameters for the Design of Bioequivalence Studies on Moderately Lipophilic, Moderately to Highly Protein Bound Drugs Using Dermal Open Flow Microperfusion (dOFM)
Condition: Dermatology/Skin - Other; Dermal Pharmacokinetic Measurements
Study type: Interventional

Summary: 
      The overall aim of this clinical pilot study is to develop an optimal design (e.g. dose,
      study duration) for the main clinical study. In the main study factors that influence dOFM
      data variability will be measured to develop a general BE testing method using dOFM for
      dermatological drug products.
    

Detailed description: 
      In this herein described pilot study 6 subjects will receive three different topical doses of
      Lidocaine 2.5% and Prilocaine 2.5% cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS
      LABORATORIES UT INC, US ) to select an optimal dose for the main study. Oraqix® gel (2.5%
      lidocaine, 2.5% prilocaine, Dentsply Pharmaceutical Inc., US) will be applied to assess
      whether it can be used as negative control in the main study. Blood samples will also be
      drawn at prior to dosing to establish a baseline, and at defined time points post-dose to
      assess systemic drug levels. Furthermore, lateral diffusion from a dosed site to an adjacent
      (non-dosed) test site will be evaluated in this pilot study. Different non-invasive devices
      will be tested to identify influencing factors for skin penetration in order to complete the
      available information on skin characteristics for the main study.

      This pilot will be a single center, open label, exploratory research study to assess the
      dermal PK of marketed topical formulations of lidocaine/prilocaine in six healthy volunteers
      using dOFM. The study will be performed at the Clinical Research Center of the Medical
      University of Graz/Austria.The study comprises three visits, a screening visit (Visit 1), a
      study visit of approximately 28 h (Visit 2) for application of dermatological drug products,
      and an End-of-Study visit (Visit 3). In Visit 2 each subject will have nine test sites, four
      on the left thigh, four on the right thigh (resulting in 8 test sites on both thighs) and one
      on the arm. Each of the nine test site will have 2 dOFM probes resulting in 18 dOFM probes
      per subject. On six of the eight test sites on the thighs three different doses of Lidocaine
      2.5% and Prilocaine 2.5% cream cream will be applied (5 mg/cm², 10 mg/cm² or 15 mg/cm²) to
      assess the dose for the main study. On another test site on the thighs Oraqix® gel will be
      applied to check if Oraqix® can be used as negative control in the main study. On the
      remaining test site on the thighs as well as on the test site on the arm no products will be
      applied to test for potential cross-talk between test sites by lateral diffusion and systemic
      redistribution, resulting in seven treated and two non-treated sites per subject.
      Additionally 8 blood samples will be drawn to rule out systemic appearance of lidocaine
      and/or prilocaine. Further, devices to identify possible factors influencing skin penetration
      will be measured on each thigh (e.g. TEWL).
    

Intervention name(s): Dermal pharmacokinetic measurement; Lidocaine and prilocaine cream; Oraqix® gel; dOFM-System; Blood sampling
Intervention type(s): Other; Drug; Drug; Device; Procedure
Intervention description(s): Each subject will have 9 test sites: 4 on the left thigh, 4 on the right thigh, 1 on the arm
Each test site receives 2 dOFM probes
Dosing:
2 test sites: 15 mg/cm² lidocaine and prilocaine cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS LABORATORIES UT INC, US)
2 test sites: 10 mg/cm² lidocaine and prilocaine cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS LABORATORIES UT INC, US)
2 test sites: 5 mg/cm² lidocaine and prilocaine cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS LABORATORIES UT INC, US)
1 test site: 10 mg/cm² Oraqix® gel (2.5% lidocaine, 2.5% prilocaine, Dentsply Pharmaceutical Inc., US/Dentsply DETRY GmbH, Germany)
2 test sites: untreated test site
ISF sampling: 24 hours post-dose
Blood sampling: 7 samples post-dose; lidocaine and prilocaine cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS LABORATORIES UT INC, US) will be applied to 6 test sites per subject; Oraqix® gel (2.5% lidocaine, 2.5% prilocaine, Dentsply Pharmaceutical Inc., US/Dentsply DETRY GmbH, Germany) will be applied to 1 test site per subject; Dermal open flow microperfusion system will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentrations over 24 hours; 8 blood samples will be collected in order to assess systemic lidocaine/prilocaine concentrations pre-dose (1 sample) and 24 hours post dose (7 samples)
Intervention MeSH terms: Lidocaine; Prilocaine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dermal open flow microperfusion; dOFM