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HealthyNCT03813030

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

A study testing Intravenous infusion of lidocaine, Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA) and Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria) in people with Healthy and Dermal Pharmacokinetic Measurement, run by Joanneum Research Forschungsgesellschaft mbH at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy, Dermal Pharmacokinetic Measurement
What is being tested?
Intravenous infusion of lidocaine, Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA) and Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteAustria
Study dates
16 Jan 2019to 28 Aug 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 32Show fewer
  • 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.
  • Clinically significant abnormal 12-lead ECG at screening, as deemed by the investigator.
  • Positive results to the test for hepatitis B antigen or hepatitis C antibodies.
  • Positive HIV test.
  • Positive alcohol breath test.
  • Blood donation within 30 days or significant loss of blood or plasma (more than 550 ml) within 90 days prior to screening.
  • Subject who have received an investigational drug within 30 days prior to the initial dose of study medication.
  • Known or suspected allergy/hypersensitivity to lidocaine or prilocaine, known history of sensitivity to local anesthetics of the amide type or to any other component of the product, other related products, or any inactive ingredients.
  • Tattoos or broken and/or damaged skin at the application areas.
  • Active skin diseases like psoriasis or atopic dermatitis, as judged by the investigator.
  • Scarring at the anterior part of the thighs.
  • Subjects prone to keloid or hypertrophic scar formation or any known wound healing disorder.
  • Recent and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.), as judged by the investigator.
  • Not willing to avoid excessive sun exposure, steam baths, sauna, swimming and other strenuous activities for 14 days after Visit 2 to ensure good tissue regeneration.
  • Not willing to refrain from shaving the planned application sites or using skin care products on the planned application sites for at least 5 days prior to start of Visit 2.
  • Pronounced hairiness on the planned application sites that may negatively affect BE testing.
  • Known allergy/hypersensitivity to any of the materials/supplies used during the study.
  • Presence of needle phobia.

Trial locations and contacts

1 site in 1 country.

Austria1 site

  • Clinical Research Center, Medical University Graz

    Graz, 8010

Other trials in Austria

About this study

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.

Read the 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.

Being tested
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
Keywords
Dermal open flow microperfusion, Dermal microdialysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intravenous infusion of lidocaineProcedure or surgery

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

  • 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

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

    Intravenous infusion in clearance visit

  • Dermal open flow microperfusionDevice

    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 MicrodialysisDevice

    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

  • Blood sampling in dermal sampling visitProcedure or surgery

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

  • Blood sampling in clearance visitProcedure or surgery

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

Study groups in NCT03813030
Study groupRoleWhat they receive
Pilot StudyExperimentalDermal-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.
Receives: 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 StudyExperimentalDermal-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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 13 hours

  2. 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).

    Measured: 13 hours

  3. 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).

    Measured: 13 hours

  4. 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).

    Measured: 13 hours

  5. 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.

    Measured: 13 hours

  6. 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.

    Measured: 13 hours

Secondary outcomes (1)

  1. Lidocaine clearance (Pivotal study) - 20 participants

    Blood concentration (ng/mL) of lidocaine will be measured to obtain the concentration-time curves and to calculated the individual lidocaine clearance (L/min).

    Measured: 6 hours post dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2019
  2. Study start16 Jan 2019
  3. Primary completion28 Aug 2019
  4. Study completion28 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Sequential
Model description
Pilot Study with 6 participants and pivotal study with 20 participants
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03813030
Sponsor's protocol ID
FDA02_AIM4
Other IDs
2018-002507-33, 2018
Status last verified
Jul 2020
First submitted
17 Jan 2019
Last updated
10 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27539717

  • 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.

    PubMed 27271272

  • 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.

    PubMed 5285383

  • 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.

    PubMed 16874309

  • 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.

    PubMed 29739540

  • Tiffner KI, Ramezanli T, Boulgaropoulos B, Birngruber T, Bodenlenz M, Lackner BC, Raml R, Raney SG, Sinner F. The Impact of Systemic Redistribution on Cutaneous Pharmacokinetic-Based Bioequivalence: An In vivo Dermal Open Flow Microperfusion Study for Lidocaine and Prilocaine. Eur J Pharm Sci. 2026 Sep 23:107673. doi: 10.1016/j.ejps.2026.107673. Online ahead of print.

    PubMed 42777886

Questions about this trial

What is this clinical trial studying?

A study testing Intravenous infusion of lidocaine, Lidocaine 2.5% and Prilocaine 2.5% cream", USP (2.5% lidocaine, 2.5% prilocaine, Actavis Pharma incorporated, USA) and Lidocorit 2%-Ampullen" (Gebro Pharma Gesellschaft mit beschränkter Haftung, Austria) in people with Healthy and Dermal Pharmacokinetic Measurement, run by Joanneum Research Forschungsgesellschaft mbH at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under the dermal concentration versus time curve for lidocaine (pilot study: 6 participants, pivotal study: 20 participants) (time frame: 13 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03813030, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.

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