Bioequivalence of Flurbiprofen Lozenge vs Strepfen

Study Overview
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Brief Summary
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The present study has been designed to compare flurbiprofen pharmacokinetic profile after administration of flurbiprofen 8.75 mg lozenges, marketed by ACRAF, S.p.A., Italy (test product), and the marketed Strepfen 8.75 mg honey and lemon lozenges reference product. (Reckitt Benckiser Portugal SA).

Detailed Description
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This is a single dose, open-label, randomised, 2-way cross-over bioequivalence study aimed to compare the bioavailability and the plasma pharmacokinetic profile of flurbiprofen after single dose administration of test and reference formulations.

Official Title
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Bioequivalence Study of Flurbiprofen 8.75 mg Lozenge vs. the Reference Product Strepfen 8.75 mg Lozenge in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Flurbiprofen Test 8.75 MG
* Drug: Flurbiprofen Reference 8.75 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent: signed written informed consent before inclusion in the study. Sex and Age: males and females, 18-55 years old inclusive. Habits: non smokers. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive. Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min at rest in the sitting position. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study. Contraception and fertility (women only): females of child-bearing potential must be using at least one of the following reliable methods of contraception: Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit A male sexual partner who agrees to use a male condom with spermicide A sterile sexual partner Women of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, pregnancy test result must be negative at screening and day -1. Exclusion Criteria: Electrocardiogram (12-lead ECG in supine position): clinically significant abnormalities. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study; subjects with dry mouth conditions or with any other diseases/problems of the mouth which the investigator considers may affect the outcome of the study. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study. Medications: medications, including over the counter (OTC) medications and herbal remedies, in particular flurbiprofen, for 2 weeks before the start of the study. Hormonal contraceptives for females will be allowed Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study Blood donation: blood donations for 3 months before this study Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2015-2020 (9)], or caffeine abuse (>5 cups coffee/tea/day); smokers Drug test: positive result at the drug test at screening or day-1 Alcohol test: positive alcohol breath test at day -1 Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians Pregnancy (women only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single dose, open-label, randomised, 2-way cross-over bioequivalence study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flurbiprofen 8.75 mg<br>Flurbiprofen 8.75 mg lemon and honey flavour lozenge | Drug: Flurbiprofen Test 8.75 MG<br>* Subjects will be asked to swallow saliva before dosing. For each administration, subjects will move the lozenge around in their mouth, suck on the lozenge continually for 15 min and swallow saliva at any time during the product administration procedures, being very careful not to swallow the lozenge.<br>|
| Active Comparator: Strepfen 8.75 mg<br>Strepfen 8.75 mg lemon and honey lozenge | Drug: Flurbiprofen Reference 8.75 MG<br>* Subjects will be asked to swallow saliva before dosing. For each administration, subjects will move the lozenge around in their mouth, suck on the lozenge continually for 15 min and swallow saliva at any time during the product administration procedures, being very careful not to swallow the lozenge.<br>* Other names: Strepfen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration | to evaluate the rate (Cmax) of absorption of flurbiprofen in plasma after single dose administration | pre-dose (0), 10, 20, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose | 
| Area under the plasma concentration-time curve 0-t | to evaluate the extent of absorption of flurbiprofen in plasma after single dose administration | pre-dose (0), 10, 20, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to achieve Cmax | to evaluate time to achieve Cmax | pre-dose (0), 10, 20, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose | 
| tlag | to evaluate time prior to the first measurable (i.e. above lower quantification limit) concentration | pre-dose (0), 10, 20, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose | 
| Relative bioavailability of flurbiprofen in plasma | to evaluate relative bioavailability of flurbiprofen in plasma | pre-dose (0), 10, 20, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose | 
| Palatability | to assess the palatability of test and reference formulations using a 0-100 mm VAS where 0 mm indicated not pleasant at all and 100 mm indicated very pleasant. | 2 times through the two week study period | 
| Treatment-Emergent Advers Events | to evaluate number of TEAEs and number of subjects with TEAEs | through the two week study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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flurbiprofen, lozenge, Strepfen, bioequivalence