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

NCT03813030 | Completed

• 2 other identifiers: FDA02_AIM42018-002507-33
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Dermal Pharmacokinetic Measurement

Keywords

Dermal open flow microperfusion; Dermal microdialysis

Outcome Measures

Primary Outcomes (6)

• Area under the dermal concentration versus time curve for lidocaine (pilot study: 6 participants, pivotal study: 20 participants)

  Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the area under the dermal concentration versus time curve AUC (ng\*h/mL).

  13 hours

• Area under the dermal concentration time curve for prilocaine (pilot study: 6 participants, pivotal study: 20 participants)

  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).

  13 hours

• Maximal dermal concentration of lidocaine (pilot study: 6 participants, pivotal study: 20 participants)

  Dermal concentrations (ng/mL) of lidocaine will be measured to calculate the maximal dermal concentration (ng/mL).

  13 hours

• Maximal dermal concentration of prilocaine (pilot study: 6 participants, pivotal study: 20 participants)

  Dermal concentrations (ng/mL) of prilocaine will be measured to calculate the maximal dermal concentration (ng/mL).

  13 hours

• Blood lidocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)

  Lidocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.

  13 hours

• Blood prilocaine concentrations versus time curve (pilot study: 6 participants, pivotal study: 20 participants)

  Prilocaine concentrations (ng/mL) in the blood will be measured to obtain the concentration-time curves in the blood.

  13 hours

Secondary Outcomes (1)

• Lidocaine clearance (Pivotal study) - 20 participants

  6 hours post dosing

Study Arms (2)

Pilot Study

EXPERIMENTAL

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.

Drug: Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA); Device: Dermal open flow microperfusion; Device: Dermal Microdialysis; Procedure: Blood sampling in dermal sampling visit

Pivotal Study

EXPERIMENTAL

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.

Procedure: Intravenous infusion of lidocaine; Drug: Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA); Drug: Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria); Device: Dermal open flow microperfusion; Device: Dermal Microdialysis; Procedure: Blood sampling in dermal sampling visit; Procedure: Blood sampling in clearance visit

Interventions

Intravenous infusion of lidocaine PROCEDURE

Lidocaine is intravenously administered in clearance visit and blood samples are taken to calculate individual clearance of each participant.

Pivotal Study

Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA) DRUG

Topical application in dermal-sampling visit

Pilot Study; Pivotal Study

Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria) DRUG

Intravenous infusion in clearance visit

Pivotal Study

Dermal open flow microperfusion DEVICE

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

Pilot Study; Pivotal Study

Dermal Microdialysis DEVICE

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

Pilot Study; Pivotal Study

Blood sampling in dermal sampling visit PROCEDURE

1 sample is taken pre-dose and 12 samples are taken post-dose.

Pilot Study; Pivotal Study

Blood sampling in clearance visit PROCEDURE

1 sample is taken pre-dose, 3 samples during intravenous infusion and 13 samples post-dose.

Pivotal Study

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Diseases
• 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
• Presence of any acute or chronic diseases or malignancies unless deemed not clinically significant by the investigator.
• Any reason, which in the opinion of the investigator, would prevent the subject from safely participating in the study.
• Any abnormalities found at physical examination or vital signs, unless deemed not clinically significant by the investigator.
• Clinically significant abnormal laboratory evaluation results, as deemed by the investigator.

Sponsors & Collaborators

• Joanneum Research Forschungsgesellschaft mbH: lead

Study Sites (1)

Clinical Research Center, Medical University Graz

Graz, 8010, Austria

Location

Related Publications (5)

• 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.

  PMID: 27539717 BACKGROUND

• 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.

  PMID: 27271272 BACKGROUND

• 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.

  PMID: 5285383 BACKGROUND

• 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.

  PMID: 16874309 BACKGROUND

• 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.

  PMID: 29739540 BACKGROUND

MeSH Terms

Interventions

Lidocaine; Prilocaine; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Thomas Pieber, Prof.

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot Study with 6 participants and pivotal study with 20 participants

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 23, 2019
• Study Start: January 16, 2019
• Primary Completion: August 28, 2019
• Study Completion: August 28, 2019
• Last Updated: February 10, 2023

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)