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
Overview
- Phase
- Not Applicable
- Intervention
- Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA)
- Conditions
- Healthy
- Sponsor
- Joanneum Research Forschungsgesellschaft mbH
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Maximal dermal concentration of lidocaine (pilot study: 6 participants, pivotal study: 20 participants)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, adult volunteers of age 18 to 65 years (both inclusive).
- •Males or non-pregnant, non-breast feeding females using adequate contraceptive methods or abstinence.
- •Able to read, understand and sign the written informed consent form.
- •Willing to follow the protocol requirements and comply with protocol restrictions.
Exclusion Criteria
- •Social Habits
- •Smoker who is not willing to restrain from smoking during the in-house visits.
- •History of drug and/or alcohol abuse within one year of start of study as judged by the investigator.
- •Medications
- •Current treatment with systemically effective corticosteroids, monoamine oxidase (MAO) inhibitors, systemic non-selective beta-blockers, warfarin or anticholinergic drugs, or use of any medications referred in the prescription information of the products.
- •Hormonal contraceptive or hormone replacement therapy, routine vitamins or other prescribed medication are allowed if dose is stable.
- •Congenital or idiopathic methemoglobinemia.
- •History of deep vein thrombosis (DVT)/pulmonary emboly (PE)
- •Inherited blood disorders (such as factor V Leiden) who are prone to hypercoagulable state
- •Glucose-6-phosphate dehydrogenase deficiencies
Arms & Interventions
Pilot Study
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.
Intervention: Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA)
Pilot Study
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.
Intervention: Dermal open flow microperfusion
Pilot Study
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.
Intervention: Dermal Microdialysis
Pilot Study
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.
Intervention: Blood sampling in dermal sampling visit
Pivotal Study
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: Intravenous infusion of lidocaine
Pivotal Study
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: Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA)
Pivotal Study
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: Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria)
Pivotal Study
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: Dermal open flow microperfusion
Pivotal Study
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: Dermal Microdialysis
Pivotal Study
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: Blood sampling in dermal sampling visit
Pivotal Study
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: Blood sampling in clearance visit
Outcomes
Primary Outcomes
Maximal dermal concentration of lidocaine (pilot study: 6 participants, pivotal study: 20 participants)
Time Frame: 13 hours
Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the maximal dermal concentration (ng/mL).
Area under the dermal concentration versus time curve for lidocaine (pilot study: 6 participants, pivotal study: 20 participants)
Time Frame: 13 hours
Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the area under the dermal concentration versus time curve AUC (ng\*h/mL).
Maximal dermal concentration of prilocaine (pilot study: 6 participants, pivotal study: 20 participants)
Time Frame: 13 hours
Dermal concentrations (ng/mL) of prilocaine will be measured to calculate the maximal dermal concentration (ng/mL).
Blood lidocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)
Time Frame: 13 hours
Lidocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.
Area under the dermal concentration time curve for prilocaine (pilot study: 6 participants, pivotal study: 20 participants)
Time Frame: 13 hours
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).
Blood prilocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)
Time Frame: 13 hours
Prilocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.
Secondary Outcomes
- Lidocaine clearance (Pivotal study) - 20 participants(6 hours post dosing)