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
Condition: Healthy; Dermal Pharmacokinetic Measurement
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Intravenous infusion of lidocaine; Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA); Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria); Dermal open flow microperfusion; Dermal Microdialysis; Blood sampling in dermal sampling visit; Blood sampling in clearance visit
Intervention type(s): Procedure; Drug; Drug; Device; Device; Procedure; Procedure
Intervention description(s): Lidocaine is intravenously administered in clearance visit and blood samples are taken to calculate individual clearance of each participant.; Topical application in dermal-sampling visit; Intravenous infusion in clearance visit; 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; 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; 1 sample is taken pre-dose and 12 samples are taken post-dose.; 1 sample is taken pre-dose, 3 samples during intravenous infusion and 13 samples post-dose.
Intervention MeSH terms: Lidocaine; Prilocaine
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Pilot Study with 6 participants and pivotal study with 20 participants
Masking: None (Open Label)
Primary purpose: Other
Keywords: Dermal open flow microperfusion; Dermal microdialysis