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)

NCT03613207 | Completed

• 2 other identifiers: FDA02_AIM2_PILOTDRKS00012706
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dermatology/Skin - Other; Dermal Pharmacokinetic Measurements

Keywords

Dermal open flow microperfusion; dOFM

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  24 hours

• Test for lateral diffusion (crosstalk between adjacent test sites) by measuring lidocaine/prilocaine concentrations (µg/ml) of untreated test sites

  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).

  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).

  24 hours

Other Outcomes (4)

• Skin temperature [°C]

  Timepoint -3 hours (pre-dose) and timepoint 23 hours (post-dose)

• TEWL (trans-epidermal water loss) [g/(m²*h)]

  Timepoint -3 hours (pre-dose) and timepoint 23 hours (post-dose)

• Skin impedance [Ω];[S];[°]

  Timepoint -3 hours (pre-dose) and timepoint 23 hours (post-dose)

Study Arms (1)

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

Other: Dermal pharmacokinetic measurement; Drug: Lidocaine and prilocaine cream; Drug: Oraqix® gel; Device: dOFM-System; Procedure: Blood sampling

Interventions

Dermal pharmacokinetic measurement OTHER

* 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

Dermal pharmacokinetic measurement

Lidocaine and prilocaine cream DRUG

lidocaine and prilocaine cream (2.5% lidocaine, 2.5% prilocaine, ACTAVIS LABORATORIES UT INC, US) will be applied to 6 test sites per subject

Dermal pharmacokinetic measurement

Oraqix® gel DRUG

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

Dermal pharmacokinetic measurement

dOFM-System DEVICE

Dermal open flow microperfusion system will be used to collect interstitial fluid in order to assess lidocaine/prilocaine concentrations over 24 hours

Dermal pharmacokinetic measurement

Blood sampling PROCEDURE

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)

Dermal pharmacokinetic measurement

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• a. 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.
• 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.

Sponsors & Collaborators

• Joanneum Research Forschungsgesellschaft mbH: lead

Study Sites (1)

HEALTH - Joanneum Research

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

• Bodenlenz 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.

  PMID: 23581539 BACKGROUND

• Dragatin 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.

  PMID: 26439798 BACKGROUND

• Tiffner 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.

  PMID: 28328234 BACKGROUND

Related Links

• n Vivo Dermal Open Flow Microperfusion: A Novel Approach to Evaluating Topical Bioavailability and Bioequivalence

MeSH Terms

Interventions

Lidocaine; 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: August 3, 2018
• Study Start: March 22, 2018
• Primary Completion: April 10, 2018
• Study Completion: May 3, 2018
• Last Updated: August 3, 2018

Record last verified: 2018-07

Locations

AU (1)