Comparative BioavailabilityPhase 1NCT04505787
S-flurbiprofen Bioavailability Trial to Compare a Newly Developed Patch vs. a Marketed Tablet
A Phase 1 study testing Esflurbiprofen hydrogel patch 165 mg (EFHP) and Froben 100 mg comprimidos revestidos in people with Comparative Bioavailability, run by SocraTec R&D GmbH at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Comparative Bioavailability
- What is being tested?
- Esflurbiprofen hydrogel patch 165 mg (EFHP) and Froben 100 mg comprimidos revestidos
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteGermany
- Study dates
- 24 Jul 2020to 24 Sep 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 44Show fewer
- 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
- 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 of > 9 µmol/l ULN).
- positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test
- symptoms of, or diagnosis of COVID-19 within the last 14 days prior to individual enrolment of the subject
- contact to persons in risk regions as defined by the Robert Koch Institute within the last 14 days prior to individual enrolment of the subject
- direct contact to persons with symptoms of, or diagnosis of COVID-19 within the last 14 days prior to individual enrolment of the subject Lack of suitability for the clinical trial
- 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
- administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject
- regular treatment with any systemically available medication (except hormonal contraceptives and hormonal replacement therapy, e.g. estrogens, L-thyroxine)
- subjects, who report a frequent occurrence of migraine attacks
- For female subjects with childbearing potential only:
- positive pregnancy test at screening examination
- pregnant or lactating women
- female subjects who do not agree to apply highly effective contraceptive methods Administrative reasons
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
SocraTec R&D GmbH, Clinical Pharmacology Unit
Erfurt, Thuringia, 99084
About this study
Official title: Characterisation of Relative Bioavailability of a Newly Developed S-flurbiprofen Containing Patch Formulation in Comparison With a Marketed Oral Flurbiprofen Containing Tablet Formulation - a Multiple Dose, Randomised, 2-period Crossover...
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.
Read the detailed description
This single centre, open-label, randomised (order of treatments), balanced, multiple dose trial will be performed in a 2-period, 2-sequence-crossover design.
The Test Product (patch) will be applied once daily over 14 consecutive days, whereby each patch will remain applied for 24 h. Blood sampling will be performed after the 1st patch application over 24 h in order to characterise the single dose application and after the 14th patch application over 72 h in order to characterise pharmacokinetic parameters after multiple dosing including elimination phase. In between through values will be taken in the morning of specified study days to characterise steady-state built-up phase.
The Reference product will be administered after a light meal as single oral doses of 100 mg flurbiprofen three times daily (i.e. every 8 h) over 4 days. Blood sampling will be performed after the 10th tablet administration over 72 h in order to characterise pharmacokinetic parameters after multiple dosing including elimination phase. In between through values will be taken in the morning of study days 1 to 4 to characterise steady-state built-up phase.
The clinical trial will be performed as a cross-over investigation with intra-individual comparison, thus reducing variability of the pharmacokinetic parameters, which is supposed to be higher between subjects than within an individual subject.
- Conditions
- Comparative Bioavailability
- Being tested
- Esflurbiprofen hydrogel patch 165 mg (EFHP), Froben 100 mg comprimidos revestidos
- Keywords
- Bioavailability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esflurbiprofen hydrogel patch 165 mg (EFHP)Drug
patch application with PK blood sampling
Froben 100 mg comprimidos revestidosDrug
tablet administration with PK blood sampling
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Drug: Froben 100 mg comprimidos revestidos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 24 hours
Secondary outcomes (3)
Skin irritation properties for Esflurbiprofen hydrogel patch by frequency of scores
frequency of scores for local tolerability and skin irritation per time point according to "Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for ANDAs", Guidance for Industry, DRAFT. 2018 October
Measured: 16 days
Patch adhesion properties for Esflurbiprofen hydrogel patch by percentage of adhered patch area
documentation of the percentage of area that remains adhered and scoring (i.e. percentage of adhered area and scores will be matched/combined) per time point according to "Assessing Adhesion With Transdermal and Topical Delivery Systems for ANDAs", Guidance for Industry, DRAFT. 2018 October
Measured: 15 days
Adverse Events
Descriptive characterisation with regard to frequency and intensity, relationship to the IMP, action taken, outcome, and seriousness as well as period and treatment
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2020
- Study start24 Jul 2020
- Primary completion9 Sep 2020
- Study completion24 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Comparative BioavailabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- SocraTec R&D GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Teikoku Seiyaku Co., Ltd., SocraMetrics GmbH
- Responsible party
- Sponsor
- Investigators
- Frank Donath, MD, Principal investigator, SocraTec R&D GmbH Clinical Pharmacology Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04505787
- Sponsor's protocol ID
- 1378fbp19ct
- Other IDs
- 2019-003918-14, TK-254R-0101, 2019
- Status last verified
- Oct 2020
- First submitted
- 13 Jul 2020
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterisation of Relative Bioavailability of a Newly Developed S-flurbiprofen Containing Patch Formulation in Comparison With a Marketed Oral Flurbiprofen Containing Tablet Formulation - a Multiple Dose, Randomised, 2-period Crossover...
- ClinicalTrials.gov ID
- NCT04505787
- Acronym / sponsor ID
- 1378fbp19ct
- Conditions
- Comparative Bioavailability
- Keywords
- Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- SocraTec R&D GmbHUniversity, hospital or other
- Collaborators
- Teikoku Seiyaku Co., Ltd., SocraMetrics GmbH
- Study start
- 24 Jul 2020 (actual)
- Primary completion
- 9 Sep 2020 (actual)
- Study completion
- 24 Sep 2020 (actual)
- First posted
- 10 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This single centre, open-label, randomised (order of treatments), balanced, multiple dose trial will be performed in a 2-period, 2-sequence-crossover design.
The Test Product (patch) will be applied once daily over 14 consecutive days, whereby each patch will remain applied for 24 h. Blood sampling will be performed after the 1st patch application over 24 h in order to characterise the single dose application and after the 14th patch application over 72 h in order to characterise pharmacokinetic parameters after multiple dosing including elimination phase. In between through values will be taken in the morning of specified study days to characterise steady-state built-up phase.
The Reference product will be administered after a light meal as single oral doses of 100 mg flurbiprofen three times daily (i.e. every 8 h) over 4 days. Blood sampling will be performed after the 10th tablet administration over 72 h in order to characterise pharmacokinetic parameters after multiple dosing including elimination phase. In between through values will be taken in the morning of study days 1 to 4 to characterise steady-state built-up phase.
The clinical trial will be performed as a cross-over investigation with intra-individual comparison, thus reducing variability of the pharmacokinetic parameters, which is supposed to be higher between subjects than within an individual subject.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esflurbiprofen hydrogel patch | Experimental | Drug: Esflurbiprofen hydrogel patch 165 mg (EFHP)"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) |
| Froben | Active comparator | Drug: Froben 100 mg comprimidos revestidos"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 |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (44 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esflurbiprofen hydrogel patch 165 mg (EFHP)patch application with PK blood sampling | Drug | Esflurbiprofen hydrogel patch |
| Froben 100 mg comprimidos revestidostablet administration with PK blood sampling | Drug | Froben |
Primary outcome
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
Time frame: 24 hours
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
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
Time frame: 24 hours
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
3 secondary outcomes
Skin irritation properties for Esflurbiprofen hydrogel patch by frequency of scores
Time frame: 16 days
Patch adhesion properties for Esflurbiprofen hydrogel patch by percentage of adhered patch area
Time frame: 15 days
Adverse Events
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Donath, MD principal investigator
SocraTec R&D GmbH Clinical Pharmacology Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Esflurbiprofen hydrogel patch 165 mg (EFHP) and Froben 100 mg comprimidos revestidos in people with Comparative Bioavailability, run by SocraTec R&D GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.