An Exploratory Study in Healthy Volunteers to Identify Factors Influencing Bioequivalence Studies on Moderately Lipophilic Drugs Using Dermal Open Flow Microperfusion (dOFM)

NCT04050826 | Completed

• 1 other identifier: FDA02_AIM2_Main
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The overall aim of this clinical study is to develop a general bioequivalence (BE) testing method using dermal open flow microperfusion (dOFM) for dermatological drug products. In this study BE of different lidocaine/prilocaine products will be assessed and factors that influence dOFM data variability will be evaluated.

Conditions

Healthy; Dermal Pharmacokinetic Measurements

Keywords

Dermal open flow microperfusion

Outcome Measures

Primary Outcomes (4)

• Area under the dermal concentration versus time curve for lidocaine

  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 versus time curve for prilocaine

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

  13 hours

• Maximal dermal concentration of lidocaine

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

  13 hours

• Maximal dermal concentration of prilocaine

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

  13 hours

Secondary Outcomes (2)

• Blood lidocaine concentrations versus time curve

  13 hours

• Blood prilocaine concentrations versus time curve

  13 hours

Study Arms (1)

Dermal Pharmacokinetic study

EXPERIMENTAL

Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of lidocaine/ prilocaine using dOFM after topical application of three lidocaine/prilocaine products in 20 participants. After baseline sampling (1 hour pre-dose) the three lidocaine/prilocaine products will be applied and removed after 3 hours. ISF and blood sampling will be continued for a duration of 12 hours post-dose. Additionally different physical parameters (e.g. TEWL) will be measured.

Drug: Lidocaine 2.5% and Prilocaine 2.5% cream, USP (Actavis Pharma incorporated, USA); Drug: Lidocaine 2.5% and Prilocaine 2.5% cream (E. Fougera & Co. a division of Fougera Pharmaceuticals Inc., USA); Drug: Oraqix Parodontal-Gel (Dentsply Detrey GmbH, Germany); Device: Dermal open flow microperfusion; Procedure: Blood sampling

Interventions

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

Topical application

Also known as: Reference product

Dermal Pharmacokinetic study

Lidocaine 2.5% and Prilocaine 2.5% cream (E. Fougera & Co. a division of Fougera Pharmaceuticals Inc., USA) DRUG

Topical application

Also known as: Generic test product

Dermal Pharmacokinetic study

Oraqix Parodontal-Gel (Dentsply Detrey GmbH, Germany) DRUG

Topical application

Also known as: Non-equivalent test product

Dermal Pharmacokinetic 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. 16 dOFM probes will be implanted per participant (8 test-sites; 2 dOFM probes per test-site). From each dOFM probe 13 samples will be taken (1 pre-dose, 12 post-dose).

Dermal Pharmacokinetic study

Blood sampling PROCEDURE

1 sample will be taken pre-dose and 12 samples post-dose.

Dermal Pharmacokinetic 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:

• to 65 years inclusive.
• Males and/or non-pregnant, non-breast feeding 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:

• 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: 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.
• 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)

CTU - Clinical Trials Unit, 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

• 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

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

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

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 8, 2019
• Study Start: September 1, 2019
• Primary Completion: December 15, 2019
• Study Completion: July 25, 2020
• Last Updated: October 12, 2020

Record last verified: 2020-10

Locations

AU (1)