NCT04592016

Brief Summary

This will be a single center, open label, exploratory research study to assess the dermal pharmacokinetic (PK) profile of three marketed diclofenac products in 26 healthy volunteers using dermal open flow microperfusion (dOFM). This clinical study aims to assess bioequivalence (BE) of three different diclofenac products.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for not_applicable healthy

Timeline
Completed

Started Oct 2020

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 8, 2020

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

October 12, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 19, 2020

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 11, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 11, 2021

Completed
Last Updated

August 26, 2022

Status Verified

August 1, 2022

Enrollment Period

10 months

First QC Date

October 12, 2020

Last Update Submit

August 25, 2022

Conditions

Healthy

Keywords

BioequivalenceDermal open flow microperfusionDermal Pharmacokinetics Measurement

Outcome Measures

Primary Outcomes (2)

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

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

    25 hours (pilot study), 13 hours (pivotal study)

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

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

    25 hours (pilot study), 13 hours (pivotal study)

Secondary Outcomes (1)

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

    25 hours (pilot study), 13 hours (pivotal study)

Study Arms (2)

Pilot Study

EXPERIMENTAL

Dermal-sampling visit: Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of diclofenac using dermal open flow microperfusion (dOFM) after topical application of diclofenac sodium products in 6 participants. Additionally systemic appearance of diclofenac is measured by blood sampling.

Drug: Voltaren - Diclofenac sodium gel 1% (GSK, USA)Drug: Pennsaid 2 % Topical Solution (Horizon Therapeutics, USA)Device: Dermal open flow microperfusion - PilotProcedure: Blood sampling - Pilot

Pivotal Study

EXPERIMENTAL

Dermal-sampling visit: Measurement of dermal pharmacokinetic (PK) parameter (AUC, Cmax) of diclofenac using dermal open flow microperfusion (dOFM) after topical application of diclofenac sodium products in 20 participants. Additionally systemic appearance of diclofenac is measured by blood sampling.

Drug: Voltaren - Diclofenac sodium gel 1% (GSK, USA)Drug: Pennsaid 2 % Topical Solution (Horizon Therapeutics, USA)Drug: Diclofenac sodium gel 1% (Perrigo, USA)Device: Dermal open flow microperfusion - PivotalProcedure: Blood sampling - Pivotal

Interventions

Voltaren - Diclofenac sodium gel 1% (GSK, USA)DRUG

Topical application in dermal-sampling visit

Pilot StudyPivotal Study
Pennsaid 2 % Topical Solution (Horizon Therapeutics, USA)DRUG

Topical application in dermal-sampling visit

Pilot StudyPivotal Study
Diclofenac sodium gel 1% (Perrigo, USA)DRUG

Topical application in dermal-sampling visit

Pivotal Study
Dermal open flow microperfusion - PilotDEVICE

Dermal open flow microperfusion will be used to collect interstitial fluid in order to assess diclofenac concentration in the dermis. Interstitial fluid (ISF) sampling: 1 hour pre-dose and 24 hours post-dose.

Pilot Study
Dermal open flow microperfusion - PivotalDEVICE

Dermal open flow microperfusion will be used to collect interstitial fluid in order to assess diclofenac concentration in the dermis. Interstitial fluid (ISF) sampling: 1 hour pre-dose and 12 hours post-dose.

Pivotal Study
Blood sampling - PilotPROCEDURE

1 sample is taken pre-dose and 24 samples are taken post-dose.

Pilot Study
Blood sampling - PivotalPROCEDURE

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

Pivotal Study

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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 refrain from smoking during the in-house visit.
  • History of drug and/or alcohol abuse within one year of start of study as judged by the investigator.
  • Medications: Use of any medications other than hormonal contraceptive, hormone replacement therapy or routine vitamins within the 7 days or 5 half-life periods whichever is longer prior to the initial dose of study medication.
  • Diseases: Presence of any clinically relevant acute or chronic disease, which in the investigator´s opinion might jeopardise subject's safety, evaluation of results or compliance with the protocol.
  • Any reason, which in the opinion of the investigator, would prevent the subject from safely participating in the study.
  • Any abnormalities found during 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.
  • Known hypersensitivity to diclofenac or any components of the drugs.
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CTU - Clinical Trials Unit, Medical University Graz

Graz, 8010, Austria

Location

Related Publications (6)

  • 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: 27539717BACKGROUND

  • 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: 16874309BACKGROUND

  • 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: 23581539BACKGROUND

  • Bodenlenz M, Augustin T, Birngruber T, Tiffner KI, Boulgaropoulos B, Schwingenschuh S, Raney SG, Rantou E, Sinner F. Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion. Pharm Res. 2020 Sep 28;37(10):204. doi: 10.1007/s11095-020-02920-x.

    PMID: 32989514BACKGROUND

  • Dehghanyar P, Mayer BX, Namiranian K, Mascher H, Muller M, Brunner M. Topical skin penetration of diclofenac after single- and multiple-dose application. Int J Clin Pharmacol Ther. 2004 Jul;42(7):353-9. doi: 10.5414/cpp42353.

    PMID: 15605686BACKGROUND

  • Muller M, Mascher H, Kikuta C, Schafer S, Brunner M, Dorner G, Eichler HG. Diclofenac concentrations in defined tissue layers after topical administration. Clin Pharmacol Ther. 1997 Sep;62(3):293-9. doi: 10.1016/S0009-9236(97)90032-1.

    PMID: 9333105BACKGROUND

MeSH Terms

Interventions

halofantrineDiclofenacSolutions

Intervention Hierarchy (Ancestors)

PhenylacetatesAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPharmaceutical Preparations

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

Study Record Dates

First Submitted

October 12, 2020

First Posted

October 19, 2020

Study Start

October 8, 2020

Primary Completion

August 11, 2021

Study Completion

August 11, 2021

Last Updated

August 26, 2022

Record last verified: 2022-08

Locations

AU(1)