S-flurbiprofen Bioavailability Trial to Compare a Newly Developed Patch vs. a Marketed Tablet

NCT04505787 | Completed Phase 1 FDA Drug

• 3 other identifiers: 1378fbp19ct2019-003918-14TK-254R-0101
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Teikoku Seiyaku Co., Ltd. (Japan) is developing a new Esflurbiprofen Hydrogel Patch (EFHP), a transdermal product containing 165 mg of the S-enantiomer of flurbiprofen (S-flurbiprofen) as its active pharmaceutical ingredient. The present clinical trial will be conducted to characterise maximum observed systemic exposure of the newly developed EFHP (Test) vs. "Froben 100 mg" (Reference, containing 100 mg racemic flurbiprofen in a 1:1 ratio). Characterisation will be performed under steady state conditions in order to bridge the available safety information on the basis of the comparison of maximum observed systemic exposure by means of AUC0-24h,ss,P vs. AUC0-24,ss,T and Cmax,ss,P vs. Cmax,ss,T of S-flurbiprofen.

Conditions

Comparative Bioavailability

Keywords

Bioavailability

Outcome Measures

Primary Outcomes (2)

• Assessment of non-superiority of Test in comparison to Reference under steady-state conditions determined by use of AUC0-24,ss,P vs. AUC0-24,ss,T of S-flurbiprofen

  AUC0-24,ss,P = area under the plasma concentration vs. time curve from dosing time to the end of the dosing interval (profiling day after 14th patch application), calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations AUC0-24,ss,T = area under the plasma concentration vs. time profile over 24 h at profiling day from dosing time of 10th administration to 8 h after 12th administration, calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations

  24 hours

• Assessment of non-superiority of Test in comparison to Reference under steady-state conditions determined by use of Cmax,ss,P vs. Cmax,ss,T of S flurbiprofen

  Cmax,ss,P = maximum concentration in plasma within the dosing interval (profiling day after 14th patch application), obtained directly from measured values Cmax,ss,T = maximum concentration over 24 h at profiling day from dosing time of 10th administration to 8 h after 12th administration, obtained directly from measured values

  24 hours

Secondary Outcomes (3)

• Skin irritation properties for Esflurbiprofen hydrogel patch by frequency of scores

  16 days

• Patch adhesion properties for Esflurbiprofen hydrogel patch by percentage of adhered patch area

  15 days

• Adverse Events

  28 days

Study Arms (2)

Esflurbiprofen hydrogel patch

EXPERIMENTAL

"Esflurbiprofen hydrogel patch 165 mg" (EFHP) (Teikoku Seiyaku Co.), transdermal patch containing 165 mg S-flurbiprofen, once daily consecutive application over 14 days; each patch to be applied for 24 h, application site: outer ankle (same site and position for all applied patches)

Drug: Esflurbiprofen hydrogel patch 165 mg (EFHP)

Froben

ACTIVE COMPARATOR

"Froben 100 mg comprimidos revestidos" (Abbott Laboratórios, Lda., Portugal), immediate release tablets containing 100 mg flurbiprofen, oral multiple dose administration of 1 tablet three times daily (TID) over 4 consecutive days after a light meal

Drug: Froben 100 mg comprimidos revestidos

Interventions

Esflurbiprofen hydrogel patch 165 mg (EFHP) DRUG

patch application with PK blood sampling

Esflurbiprofen hydrogel patch

Froben 100 mg comprimidos revestidos DRUG

tablet administration with PK blood sampling

Froben

Eligibility Criteria

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

You may qualify if:

• 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 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 trial

You may not qualify if:

• Safety concerns
• 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 \> 160 mg/dL; HDL \< 35 mg/dL; triglycerides \> 200 mg/dL; cholesterol \> 240 mg/dL)
• 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. atopy, neurodermatitis, contact allergy, eczema, 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

Sponsors & Collaborators

• SocraTec R&D GmbH: lead
• Teikoku Seiyaku Co., Ltd.: collaborator
• SocraMetrics GmbH: collaborator

Study Sites (1)

SocraTec R&D GmbH, Clinical Pharmacology Unit

Erfurt, Thuringia, 99084, Germany

Location

MeSH Terms

Interventions

Flurbiprofen

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Frank Donath, MD

  SocraTec R&D GmbH Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: August 10, 2020
• Study Start: July 24, 2020
• Primary Completion: September 9, 2020
• Study Completion: September 24, 2020
• Last Updated: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)