To Assess the Bioavailability of TK-254RX in Comparison with Oral Flurbiprofen Tablets and the Adhesion of TK-254RX in Healthy Subjects

Teikoku Seiyaku

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Flurbiprofen tablet; Drug: Esflurbiprofen Topical System

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06823284

TK-254RX-0102

2024-513058-31-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

This study is a single-center, open-label, multiple-dose trial performed in a 2-period, 2- sequence-cross-over design in healthy volunteers. The primary purpose of this study is to assess non-superiority of the bioavailability of TK-254RX compared with that of a marketed oral flurbiprofen-containing tablet formulation in healthy volunteers in a 2-period, 2- sequence-cross-over design and evaluate adhesion of TK-254RX. Secondary purpose is to assess safety of TK-254RX and residual amount of the patch.

Enrollment: 26 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• age: 18 years 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 3 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 triall

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, tolerability, absorption and/or pharmacokinetics 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
• fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency
• galactose intolerance or Lapp lactase deficiency
• 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 > 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 administration
• 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 sites
• 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 (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)
• subject 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

TK-254RX

Experimental group

Description:

TK-254RX will be applied to left and right lower leg above ankle once daily over 5 consecutive days i.e. 10 patches will be applied totally.

Treatment:

Drug: Esflurbiprofen Topical System

Tablet (reference product)

Experimental group

Description:

Tablets containing 100mg flurbiprofen will be administered three times daily (every 8 h) over 4 consecutive days i.e. 12 tablets will be administered totally.

Treatment:

Drug: Flurbiprofen tablet