Dermatology/Skin - OtherNCT03613207
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)
A study testing Dermal pharmacokinetic measurement, Lidocaine and prilocaine cream and Oraqix® gel in people with Dermatology/Skin - Other and Dermal Pharmacokinetic Measurements, run by Joanneum Research Forschungsgesellschaft mbH at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Dermatology/Skin - Other, Dermal Pharmacokinetic Measurements
- What is being tested?
- Dermal pharmacokinetic measurement, Lidocaine and prilocaine cream and Oraqix® gel
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteAustria
- Study dates
- 22 Mar 2018to 3 May 2018
- 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
- Subject candidates must fulfill all of the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:
- 18 to 65 years inclusive,
- Males and/or non-pregnant, non-breastfeeding females (subjects need to be informed about adequate contraceptive methods).
- 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
- Subject candidates must not be enrolled in the study if they meet any of the following criteria:
- Social Habits
- Smoker who is not willing to restrain from smoking during the in-house-visit (Visit 2).
- History of drug and/or alcohol abuse within one year of start of study as judged by the investigator.
- Medications
- Use of any medications (specially medication referred in the prescription information of the products) other than hormonal contraceptive or hormone replacement therapy within the 7 days or 5 half-life periods whichever is longer prior to the initial dose of study medication.
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- Diseases
- Congenital or idiopathic methemoglobinemia
- Glucose-6-phosphate dehydrogenase deficiencies
- Presence of any acute or chronic disease 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.
- Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
- Any food allergy, intolerance, restriction or special diet that, in the opinion of the investigator, could contraindicate the subject's participation in this study.
- 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 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.) judged by the investigator.
- Not willing to avoid excessive sun exposure, steam baths, sauna, swimming and other strenuous activities between Visit 2 and the End-of-Study examination to ensure good tissue regeneration.
- Not willing to refrain from shaving the anterior of the thighs or using skin care products on the anterior of the thighs for at least 5 days prior to start of Visit 2.
- Pronounced hairiness on the thighs 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.
About this study
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.
Read the 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).
- Being tested
- Dermal pharmacokinetic measurement, Lidocaine and prilocaine cream, Oraqix® gel, dOFM-System, Blood sampling
- Keywords
- Dermal open flow microperfusion, dOFM
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dermal pharmacokinetic measurementOther
- 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 creamDrug
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® gelDrug
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
dOFM-SystemDevice
Dermal open flow microperfusion system will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentrations over 24 hours
Blood samplingProcedure or surgery
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)
| Study group | Role | What they receive |
|---|---|---|
| Dermal pharmacokinetic measurement | Experimental | Measurement of dermal pharmacokinetic (PK) parameters (AUC, Cmax) within each subject.
For dermal PK measurement cutaneous interstitial fluid will be sampled using dermal open flow microperfusion (dOFM). Additionally 8 blood samples will be drawn to rule out systemic appearance of lidocaine/prilocaine.
Each subject will have 9 test sites in total which are treated with:
* 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)
* test sites: 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 Receives: Other: Dermal pharmacokinetic measurement; Drug: Lidocaine and prilocaine cream; Drug: Oraqix® gel; Device: dOFM-System; Procedure: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Find the dose of Lidocaine 2.5% and Prilocaine 2.5% cream for the main study by comparing the concentration time curves and corresponding PK parameter Cmax of 3 different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) twice in each subject
Three different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) of Lidocaine 2.5% and Prilocaine 2.5% cream will be dosed twice in each subject in parallel.
The concentration time curves and the PK parameter Cmax of this three doses will be compared and based on this data the team will decide in collaboration with the FDA project officer which dose will be used for the main study. Thereby study duration and sampling intervals (resolution) for the main study will be defined.
Measured: 24 hours
Find the dose of Lidocaine 2.5% and Prilocaine 2.5% cream for the main study by comparing the concentration time curves and corresponding PK parameter AUC of 3 different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) twice in each subject
Three different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) of Lidocaine 2.5% and Prilocaine 2.5% cream will be dosed twice in each subject in parallel.
The concentration time curves and the PK parameter AUC of this three doses will be compared and based on this data the team will decide in collaboration with the FDA project officer which dose will be used for the main study. Thereby study duration and sampling intervals (resolution) for the main study will be defined.
Measured: 24 hours
Secondary outcomes (4)
Test for systemic exposure and systemic cross-talk by measuring lidocaine/prilocaine concentrations (µg/ml) in blood samples and ISF samples from a distant untreated test site on the arm
To measure the degree to which lidocaine and/or prilocaine are absorbed into the skin and are redistributed via the blood stream.
Lidocaine and Prilocaine concentrations will be measured in blood samples and ISF samples from a distant untreated test site on the arm. If no significant drug concentration are found in the blood samples and in the skin of the untreated topical test site on the arm (relative to the drug concentration of the treated sites) systemic exposure can be excluded.
Measured: 24 hours
Test for lateral diffusion (crosstalk between adjacent test sites) by measuring lidocaine/prilocaine concentrations (µg/ml) of untreated test sites
In one central control site, located between two test sites dosed with lidocaine and prilocaine cream, no drug product will be applied. This setup allows testing for lateral diffusion in the skin. If no significant lidocaine or prilocaine concentration (relative to the drug concentration of the treated sites) in combination with the results from outcome 2 can be found in this untreated test site, lateral diffusion can be excluded.
Measured: 24 hours
Check if Oraqix® gel can be used as 'negative control' for bioequivalence testing in the main study by comparing Oraqix® gel with Lidocaine and prilocaine cream (AUC).
On one test site Oraqix® gel will be applied with a dose of 10 mg/cm² and on another test site lidocain and prilocaine crem will be applied with a dose of 10 mg/cm².
Oraqix® gel will be compared with lidocaine and prilocaine cream by performing the average bioequivalence test. In accordance with the CDER-Guidance on "Statistical approaches on establishing bioequivalence", the 90% confidence interval for the mean difference of the AUC values will be calculated. Oraqix® gel can be used as 'negative control' if the calculated confidence interval dose not fall within the limits of 0.80 - 1.25.
Measured: 24 hours
Check if Oraqix® gel can be used as 'negative control' for bioequivalence testing in the main study by comparing Oraqix® gel with Lidocaine and prilocaine cream (Cmax).
On one test site Oraqix® gel will be applied with a dose of 10 mg/cm² and on another test site lidocain and prilocaine crem will be applied with a dose of 10 mg/cm².
Oraqix® gel will be compared with lidocaine and prilocaine cream by performing the average bioequivalence test. In accordance with the CDER-Guidance on "Statistical approaches on establishing bioequivalence", the 90% confidence interval for the mean difference of the Cmax values will be calculated. Oraqix® gel can be used as 'negative control' if the calculated confidence interval dose not fall within the limits of 0.80 - 1.25.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start22 Mar 2018
- Primary completion10 Apr 2018
- Study completion3 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Dermatology/Skin - OtherStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joanneum Research Forschungsgesellschaft mbH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Pieber, Prof., Principal investigator, Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03613207
- Sponsor's protocol ID
- FDA02_AIM2_PILOT
- Other IDs
- DRKS00012706
- Status last verified
- Jul 2018
- First submitted
- 3 Jul 2018
- Last updated
- 3 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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 27539717Bodenlenz 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 27271272Bodenlenz M, Aigner B, Dragatin C, Liebenberger L, Zahiragic S, Hofferer C, Birngruber T, Priedl J, Feichtner F, Schaupp L, Korsatko S, Ratzer M, Magnes C, Pieber TR, Sinner F. Clinical applicability of dOFM devices for dermal sampling. Skin Res Technol. 2013 Nov;19(4):474-83. doi: 10.1111/srt.12071. Epub 2013 Apr 13.
PubMed 23581539Dragatin C, Polus F, Bodenlenz M, Calonder C, Aigner B, Tiffner KI, Mader JK, Ratzer M, Woessner R, Pieber TR, Cheng Y, Loesche C, Sinner F, Bruin G. Secukinumab distributes into dermal interstitial fluid of psoriasis patients as demonstrated by open flow microperfusion. Exp Dermatol. 2016 Feb;25(2):157-9. doi: 10.1111/exd.12863. Epub 2015 Nov 23. No abstract available.
PubMed 26439798Tiffner K, Boulgaropoulos B, Hofferer C, Birngruber T, Porksen N, Linnebjerg H, Garhyan P, Lam ECQ, Knadler MP, Pieber TR, Sinner F. Quantification of Basal Insulin Peglispro and Human Insulin in Adipose Tissue Interstitial Fluid by Open-Flow Microperfusion. Diabetes Technol Ther. 2017 May;19(5):305-314. doi: 10.1089/dia.2016.0384. Epub 2017 Mar 22.
PubMed 28328234
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03613207
- Acronym / sponsor ID
- FDA02_AIM2_PILOT
- Keywords
- Dermal open flow microperfusion, dOFM
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Joanneum Research Forschungsgesellschaft mbHUniversity, hospital or other
- Study start
- 22 Mar 2018 (actual)
- Primary completion
- 10 Apr 2018 (actual)
- Study completion
- 3 May 2018 (actual)
- First posted
- 3 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dermal pharmacokinetic measurement | Experimental | Other: Dermal pharmacokinetic measurement, Drug: Lidocaine and prilocaine cream, Drug: Oraqix® gel, Device: dOFM-System, Procedure: Blood samplingMeasurement of dermal pharmacokinetic (PK) parameters (AUC, Cmax) within each subject. For dermal PK measurement cutaneous interstitial fluid will be sampled using dermal open flow microperfusion (dOFM). Additionally 8 blood samples will be drawn to rule out systemic appearance of lidocaine/prilocaine. Each subject will have 9 test sites in total which are treated with: * 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) * test sites: 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject candidates must fulfill all of the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:
- 18 to 65 years inclusive,
- Males and/or non-pregnant, non-breastfeeding females (subjects need to be informed about adequate contraceptive methods).
- Able to read, understand, and sign the written informed consent form.
- Willing to follow the protocol requirements and comply with protocol restrictions.
Key exclusion criteria (31 listed)
- Subject candidates must not be enrolled in the study if they meet any of the following criteria:
- Social Habits
- Medications
- Diseases
- Any reason which, in the opinion of the investigator, would prevent the subject from safely participating in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dermal pharmacokinetic measurement* 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 | Other | Dermal pharmacokinetic measurement |
| Lidocaine and prilocaine creamlidocaine and prilocaine cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS LABORATORIES UT INC, US) will be applied to 6 test sites per subject | Drug | Dermal pharmacokinetic measurement |
| Oraqix® gelOraqix® gel (2.5% lidocaine, 2.5% prilocaine, Dentsply Pharmaceutical Inc., US/Dentsply DETRY GmbH, Germany) will be applied to 1 test site per subject | Drug | Dermal pharmacokinetic measurement |
| dOFM-SystemDermal open flow microperfusion system will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentrations over 24 hours | Device | Dermal pharmacokinetic measurement |
| Blood sampling8 blood samples will be collected in order to assess systemic lidocaine/prilocaine concentrations pre-dose (1 sample) and 24 hours post dose (7 samples) | Procedure or surgery | Dermal pharmacokinetic measurement |
Primary outcome
Find the dose of Lidocaine 2.5% and Prilocaine 2.5% cream for the main study by comparing the concentration time curves and corresponding PK parameter Cmax of 3 different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) twice in each subject
Time frame: 24 hours
Three different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) of Lidocaine 2.5% and Prilocaine 2.5% cream will be dosed twice in each subject in parallel. The concentration time curves and the PK parameter Cmax of this three doses will be compared and based on this data the team will decide in collaboration with the FDA project officer which dose will be used for the main study. Thereby study duration and sampling intervals (resolution) for the main study will be defined.
Find the dose of Lidocaine 2.5% and Prilocaine 2.5% cream for the main study by comparing the concentration time curves and corresponding PK parameter AUC of 3 different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) twice in each subject
Time frame: 24 hours
Three different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) of Lidocaine 2.5% and Prilocaine 2.5% cream will be dosed twice in each subject in parallel. The concentration time curves and the PK parameter AUC of this three doses will be compared and based on this data the team will decide in collaboration with the FDA project officer which dose will be used for the main study. Thereby study duration and sampling intervals (resolution) for the main study will be defined.
4 secondary outcomes
Test for systemic exposure and systemic cross-talk by measuring lidocaine/prilocaine concentrations (µg/ml) in blood samples and ISF samples from a distant untreated test site on the arm
Time frame: 24 hours
Test for lateral diffusion (crosstalk between adjacent test sites) by measuring lidocaine/prilocaine concentrations (µg/ml) of untreated test sites
Time frame: 24 hours
Check if Oraqix® gel can be used as 'negative control' for bioequivalence testing in the main study by comparing Oraqix® gel with Lidocaine and prilocaine cream (AUC).
Time frame: 24 hours
Check if Oraqix® gel can be used as 'negative control' for bioequivalence testing in the main study by comparing Oraqix® gel with Lidocaine and prilocaine cream (Cmax).
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
- Background: PubMed 27539717Bodenlenz 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.
- Background: PubMed 27271272Bodenlenz 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.
- Background: PubMed 23581539Bodenlenz M, Aigner B, Dragatin C, Liebenberger L, Zahiragic S, Hofferer C, Birngruber T, Priedl J, Feichtner F, Schaupp L, Korsatko S, Ratzer M, Magnes C, Pieber TR, Sinner F. Clinical applicability of dOFM devices for dermal sampling. Skin Res Technol. 2013 Nov;19(4):474-83. doi: 10.1111/srt.12071. Epub 2013 Apr 13.
- Background: PubMed 26439798Dragatin C, Polus F, Bodenlenz M, Calonder C, Aigner B, Tiffner KI, Mader JK, Ratzer M, Woessner R, Pieber TR, Cheng Y, Loesche C, Sinner F, Bruin G. Secukinumab distributes into dermal interstitial fluid of psoriasis patients as demonstrated by open flow microperfusion. Exp Dermatol. 2016 Feb;25(2):157-9. doi: 10.1111/exd.12863. Epub 2015 Nov 23. No abstract available.
- Background: PubMed 28328234Tiffner K, Boulgaropoulos B, Hofferer C, Birngruber T, Porksen N, Linnebjerg H, Garhyan P, Lam ECQ, Knadler MP, Pieber TR, Sinner F. Quantification of Basal Insulin Peglispro and Human Insulin in Adipose Tissue Interstitial Fluid by Open-Flow Microperfusion. Diabetes Technol Ther. 2017 May;19(5):305-314. doi: 10.1089/dia.2016.0384. Epub 2017 Mar 22.
- n Vivo Dermal Open Flow Microperfusion: A Novel Approach to Evaluating Topical Bioavailability and BioequivalenceLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Pieber, Prof. principal investigator
Medical University of Graz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dermal pharmacokinetic measurement, Lidocaine and prilocaine cream and Oraqix® gel in people with Dermatology/Skin - Other and Dermal Pharmacokinetic Measurements, 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 5 inclusion and 31 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 3 Aug 2018. 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?
Find the dose of Lidocaine 2.5% and Prilocaine 2.5% cream for the main study by comparing the concentration time curves and corresponding PK parameter Cmax of 3 different doses (5 mg/cm², 10 mg/cm² and 15 mg/cm²) twice in each subject (time frame: 24 hours). The study lists 2 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 NCT03613207, which also lists 5 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 3 Aug 2018.