Evaluation of bioavailability, adhesion and tolerability of Flector Unidie® medicated plaster applied once a day for 5 consecutive days to healthy volunteers Not Applicable
Conditions
Interventions
One (1) Flector Unidie® (piroxicam) 14 mg medicated plaster will be applied once a day (o.d.) for 5 consecutive days to healthy men and women. The medicated plaster will be applied each morning at 08:
Sponsors
IBSA Institut Biochimique (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and Age: men/women, 18-55 years old inclusive 3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive 4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-99 bpm, measured after 5 min at rest in the sitting position 5. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the Investigator and to comply with the requirements of the entire study 6. Contraception and fertility (women only): women of child-bearing potential must be using at least one of the following reliable methods of contraception: 6.1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit 6.2. 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 6.3. A male sexual partner who agrees to use a male condom with spermicide 6.4. A sterile sexual partner. or: True abstinence (i.e., refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), lactational amenorrhea, and withdrawal are not acceptable. 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
Exclusion criteria: 1. Electrocardiogram (ECG) 12-leads (supine position): clinically significant abnormalities 2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study 3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness 4. Application site: diseased skin, skin wounds, open injuries or tattoos on both deltoid muscles or any other physical/medical condition which could interfere with the objectives of the study 5. 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 6. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study 7. Medications: medications, including over-the-counter (OTC) medications (in particular, non-steroidal anti-inflammatory drugs) and herbal remedies, for 2 weeks before the start of the study. Hormonal contraceptives for women will be allowed 8. 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 9. Blood donation: blood donations for 3 months before this study 10. Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for women and >2 drinks/day for men, defined according to the USDA Dietary Guidelines 2020-2025 (18)], caffeine (>5 cups coffee/tea/day) or tobacco abuse (?10 cigarettes/day) 11. SARS-CoV-2 test: positive COVID-19 rapid test at screening or Day -1 12. Drug test: positive result at the drug test at screening or Day -1 13. Alcohol test: positive alcohol saliva test at screening or Day -1 14. Diet: abnormal diets (3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians and vegans 15. Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma piroxicam concentration profile (drug absorption, distribution, metabolism and excretion) and pharmacokinetic parameters (Cmax0-24h, C24h, AUC0-24h, tmax0-24h, Cmin0-24h, Cave0-24h, Flu% [0-24h], AUC0-t, AUC0-72 and, if feasible, AUC0-inf, and t1/2) after the last repeated application of Flector Unidie® 14 mg medicated plaster. Plasma concentrations of piroxicam will be measured using a validated bioanalytical method on Days 1, 2, 3 and 4 at pre-application (0), on Day 5 at pre-application (0) and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 16 h post-application (the collection at 16 h post-dose could take place on Day 6, it depends upon the IMP administration time), on Day 6 at 24 and 36 h post-application, on Day 7 at 48 h post-application and on Day 8 at 72 h post application. In detail, the following pharmacokinetic parameters will be measured: Cmax0-24h: maximum plasma concentration in the 24 h interval achieved after repeated applications; C24h: plasma concentration at the time-point of 24 h after repeated applications; AUC0-24h: area under the concentration-time curve in the 24 h interval, calculated with the linear trapezoidal method; tmax0-24 h: time to achieve Cmax0-24 h; Cmin0-24h: minimum plasma concentration in the 24 h interval achieved after repeated applications; Cave0-24h: average plasma concentration in the 24h interval achieved after repeated applications, calculated as AUC0-24h/0-24h; Flu%(0-24h): percentage of fluctuation, calculated as 100*(Cmax0-24h-Cmin0-24h)/Cave0-24h; AUC0-t: area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method; AUC0-72: area under the concentration-time curve from administration to 72 h post-dose, calculated with the linear trapezoidal method; AUC0-inf: area under the concentration-time curve extrapolated to infinity, calculated, if feasible, as AUC0-t + Ct/?z, where Ct is the last measurable drug concentration; t1/2: half-li | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Adhesion scores and estimated percentage of adhered plaster area for Flector Unidie® 14 mg medicated plaster. Adhesion of the plaster will be evaluated at 4, 8, 12, 16 and 20 h post-application. The assessment will be performed using the following 5-point scale: - 0 >= 90% adhered (essentially no lift off of the skin) - 1 >= 75% to = 50% to 0% to < 50% adhered (the plaster is not detached, but more than half of the plaster lifts off the skin without falling off) - 4 0% adhered (the plaster is detached and is completely off the skin). In addition, at each time point, the actual percentage adhesion value (%) will be estimated by the Investigator. 2. Treatment-emergent adverse events during the study 3. Vital signs (blood pressure, heart rate) measured at the screening visit, on Day 7 at 48 h post-application (before discharge) and at the final visit/ETV 4. Local tolerability, assessed by the Investigator at the application site before the first plasters application on Day 1 (pre-application) and after plasters removal on Days 2, 3, 4, 5 and 6. Local tolerability will be assessed by giving a score to each of the tolerability parameters (application site erythema, application site dryness, application site swelling and application site exfoliation) according to a 4-grade scale (0 None, 1 Mild, 2 Moderate, 3 Severe) 5. Physical examination (including body weight) at screening and final visit/ETV 6. Laboratory parameters at screening and final visit/ETV. | — |
Countries
Switzerland
Contacts
Public ContactSerena Caversazio
Outcome results
None listed