To Assess the Effect of the Special Condition on the Pharmacokinetics and Tolerability of the Esflurbiprofen Topical System (EFTS) in Healthy Volunteers.

A Randomized, Four-way Change-over Study to Evaluate the Effect of Moderate Heat, Occlusion, and Moderate Exceise on the Pharmacokinetics and Tolerability of the Esflurbiprofen Topical System in Healthy Volunteers

This study is a single-center, open-label, single-dose trial performed in a randomized, four-way, change-over design in healthy volunteers. The primary purpose of this study is to evaluate the effect of moderate heat, occlusion, and moderate exercise on pharmacokinetics. The secondary purpose is to characterize the effect of special conditions on the bioavailability and to evaluate patch adhesion and safety of TK-254RX and a residual amount of the patch.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Esflurbiprofen Topical System

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Erfurt
    • Mainzerhofplatz, Erfurt, Germany, 99084
      • SocraTec R&D GmbH Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• age: 18 to 64 years (inclusive)
• body-mass index (BMI): ≧18.5 kg/m² and ≦ 30.0 kg/m²
• good state of health
• non-smoker or ex-smoker for at least 6 months
• written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial

Exclusion Criteria:

• existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
• existing or history of hypertension and/or heart failure
• existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient
• existing gastrointestinal diseases or pathological findings, which might interfere with the safety and tolerability of the active ingredient
• history of gastrointestinal bleeding or perforation related to previous NSAID therapy
• active, or history of ulcerative colitis, Crohn's disease, peptic ulceration or gastrointestinal haemorrhage
• existing metabolic, endocrine and/or immunologic diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient
• diabetes mellitus
• hyperlipidaemia (LDL > 4.16 mmol/l, HDL < 0.91 mmol/l, triglycerides > 2.28 mmol/l, cholesterol > 6.24 mmol/l)
• history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
• presence or history of acute or chronic diseases of the skin (e.g., atopic dermatitis (eczema), neurodermatitis, contact allergy, psoriasis, vitiligo, melanoma, squamous cell carcinoma), any dermatological condition or skin sensitivity which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
• existing or history of bronchial asthma
• known allergic reactions (e.g., bronchospasm, rhinitis, angioedema, or urticaria) to the active ingredients used, to acetylsalicylic acid or other NSAIDs, or to constituents of the pharmaceutical preparations
• history of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
• systolic blood pressure < 90 or > 139 mmHg
• diastolic blood pressure < 60 or > 89 mmHg
• heart rate < 50 bpm or > 90 bpm
• QTc interval > 450 ms for men and > 470 ms for women
• laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator
• ASAT > 20% ULN, ALAT > 10% ULN, bilirubin > 20% ULN (except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) and creatinine > 0.1 mg/dL ULN (limit of > 0.1 mg/dL correspondents to of > 9 µmol/l ULN).
• positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test
• vaccination against COVID-19 within the last 4 weeks prior to individual intended IMP application
• skin abnormality (e.g., tattoo (including tattoo that was removed), scar, sunburn, or obvious difference in skin colour), open sores, or excessive hair at the application site
• acute or chronic diseases which may interfere with the pharmacokinetics of the IMP
• history of or current drug or alcohol dependence
• positive alcohol or drug test at screening examination
• regular intake of alcoholic food or beverages of ≥ 24 g pure ethanol for male or ≥ 12 g pure ethanol for female per day
• subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
• regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
• blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject
• participation in a clinical trial with administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject
• simultaneous participation in another clinical trial with active ingredients
• regular treatment with any systemically available medication (except sexual and thyroid hormones)
• subjects, who report a frequent occurrence of migraine attacks
• positive pregnancy test at screening examination
• pregnant or lactating women
• female subjects who do not agree to apply highly effective contraceptive methods
• subject is vulnerable such as detained or committed to an institution by a court of law or by legal authorities or close affiliation with the sponsor or the investigational site (e.g., a close relative of the investigator, dependent person (e.g., employee of or student at the investigational site), employee of the sponsor or affiliates)
• subjects suspected or known not to follow instructions
• subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TK-254RX; TK-254RX will be applied with no special condition	Drug: Esflurbiprofen Topical System; TK-254RX will be applied for one day
Experimental: TK-254RX with heat; TK-254RX will be applied with moderate heat	Drug: Esflurbiprofen Topical System; TK-254RX will be applied for one day
Experimental: TK-254RX with occlusion; TK-254RX will be applied with occlusion	Drug: Esflurbiprofen Topical System; TK-254RX will be applied for one day
Experimental: TK-254RX with exercise; TK-254RX will be applied with 3 moderate exercise sessions	Drug: Esflurbiprofen Topical System; TK-254RX will be applied for one day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the effect of each intervention by Area under the plasma concentration versus time curve over 24 hours (AUC0-24) of S-flurbiprofen	assessment of the effect of heat, occlusion, and moderate exercise on Test by use of AUC0-24 of S flurbiprofen	Day 1 to Day 2 for each period
Assessing the effect of each intervention by peak plasma concentration (Cmax) of S-flurbiprofen	assessment of the effect of heat, occlusion, and moderate exercise on Test determined by use of Cmax of S flurbiprofen	Day 1 to Day 2 for each period
Assessing the effect of each intervention by area under the plasma concentration versus time curve from patch application to last measurement time point with a concentration value above lower limit of quantitation (AUC0-tlast) of S-flurbiprofen	assessment of the effect of heat, occlusion, and moderate exercise on Test determined by use of AUC0-tlast of S flurbiprofen	Day 1 to Day 4 for each period
Assessing the effect of each intervention by area under the plasma concentration versus time curve from patch application to infinity (AUC0-inf) of S-flurbiprofen	assessment of the effect of heat, occlusion, and moderate exercise on Test determined by use of AUC0-inf of S flurbiprofen	Day 1 to Day 4 for each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the effect of each intervention by area under the curve over 24 hours (AUC0-24)	Characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by AUC0-24 of R-flurbiprofen and metabolites, if applicable	Day 1 to Day 2 for each period
Assessing the effect of each intervention by peak plasma concentration (Cmax)	Characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by Cmax of R-flurbiprofen and metabolites, if applicable	Day 1 to Day 2 for each period
Assessing the effect of each intervention by area under the plasma concentration versus time curve from patch application to last time point with a concentration value above lower limit of quantitation (AUC0-tlast)	Characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by AUC0-tlast of R-flurbiprofen and metabolites, if applicable	Day 1 to Day 4 for each period
Assessing the effect of each intervention by area under plasma concentration versus time curve from patch application to infinity (AUC0-inf)	Characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by AUC0-inf of R-flurbiprofen and metabolites, if applicable	Day 1 to Day 4 for each period
Assessing the effect of each intervention by percentage of area under the plasma concentration versus time curve extrapolated to infinity to area under the plasma concentration versus time curve from 0 hour to infinity (AUCexpol%)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by AUCexpol% of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 4 for each period
Assessing the effect of each intervention by concentration at the last time point with concentration value above lower limit of quantitation (Clast)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by Clast of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 2 for each period
Assessing the effect of each intervention by time point to reach peak plasma concentration (Tmax)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by Tmax of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 4 for each period
Asssessing the effect of each intervention by last time point with concentration value above the lower limit of quantitation (Tlast)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by Tlast of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 4 for each period
Assessing the effect of each intervention by apparent terminal elimination half-life (T1/2)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by T1/2 of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 4 for each period
Assessing the effect of each intervention by apparent terminal elimination rate constant determined by log-linear regression (Lz)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by Lz of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 4 for each period
Assessing the effect of each intervention by time point before first concentration balue above the lower limit quantitation (Tlag)	characterisation of the effect of heat, occlusion, and moderate exercise on the bioavailability of Test determined by Tlag of S flurbiprofen as well as R flurbiprofen and their metabolites, if applicable	Day 1 to Day 2 for each period
Characterization of EFTS adhesion	measuring patch adhesion area by percentage of visually by site staff with remaining patch adhered	Day 2 for each period
Characterization of local tolerability	Assessing the local tolerability by using the 8-point dermal response and other effects score according to FDA recommendation	with in 5 minutes after removal of each patch as well as 12 hours, 24 hours, and 36 hours after removal for each period
Recording adverse event and serious adverse event		Day 1 to Day 4 for each period
Residual amount	residual amout of S-flurbiprofen in used patch for each period	Day 2 for each period

Collaborators and Investigators

• Sponsor: Teikoku Seiyaku Co., Ltd.
• Collaborators: SocraTec R&D GmbH; SocraMetrics GmbH; HWI pharma services GmbH
• Investigators: Study Chair: Kenichi Nishiyama, Teikoku Seiyaku Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Actual): April 3, 2025
• Study Completion (Actual): April 14, 2025

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: TK-254RX-0104; 2024-513059-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No