Local tolerability and bioavailability of a new medicated plaster containing diclofenac epolamine (DHEP) Not Applicable
Conditions
Interventions
One DHEP medicated plaster (T1: diclofenac epolamine 360 mg, corresponding to 278.4 mg diclofenac
T2: diclofenac epolamine 180 mg, corresponding to 139.2 mg diclofenac
R: diclofenac epolamine 182 mg, corresponding to 129.3 mg diclofenac) is applied once a day for 2 consecutive days to each healthy male or female volunteer in three study periods according to a three-
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: males and females, 18-45 years old inclusive 3. Body Mass Index (BMI): 18.5-30 kg/m² inclusive 4. 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 5. Full comprehension: the 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 6. Contraception and fertility (women only): women of childbearing potential must be using at least one of the following reliable methods of contraception: 6.1. Hormonal oral, implantable, intrauterine device [IUD], transdermal or injectable contraceptives for at least 2 months before the screening visit 6.2. A non-hormonal 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 Women of non-childbearing 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 of each study period
Exclusion criteria
Exclusion criteria: 1. Electrocardiogram (12-lead, supine position): clinically significant abnormalities 2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study and which the investigator considers may affect the outcome 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 at the application site 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 and herbal remedies for 2 weeks before the start of the study. Hormonal contraceptives for females 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 (population subgroup for PK analysis only): blood donations for 3 months before this study 10. 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), or caffeine abuse (>5 cups coffee/tea/day) or tobacco abuse (10 or more cigarettes/day) 11. Drug test: positive result at the drug test at screening or day -1 12. Alcohol test: positive alcohol breath test at day -1 13. Diet: abnormal diets (3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians 14. Pregnancy (women only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Local tolerability is assessed as an adverse drug reaction at the application site at pre-application (on Day 1 before the first plaster application) and on Days 2 and 3 immediately after plaster removal, using a 4-grade scale to score application site erythema, dryness, swelling and exfoliation. Plaster application will be performed every day at 8:00 ± 1 h. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The pharmacokinetic profile of diclofenac assessed by comparing Cmax, AUCt, Cmin, Cave, tmax, Flu% and Frel of a new DHEP-medicated plaster applied whole (T1: 360 mg) or halved (T2: 180 mg) and the marketed DHEP medicated plaster (R: 182 mg) after blood collection on Day 1 at pre-application (0), on Day 2 at pre-application (0) and 1, 2, 3, 4, 6, 8, 10, 12, 16 post-application and on Day 3 at 24 h post-application 2. The safety of diclofenac assessed by: 2.1. Physical examination at screening and final visit/early termination visit 2.2. Body weight (kg) measured using a scale at screening and final visit/early termination visit 2.3. Vital signs (blood pressure [mmHg] and heart rate [bpm]) measured using a sphygmomanometer on Day -1 and at final visit/early termination visit 2.4. Clinical laboratory parameters (haematology, blood chemistry, urine analysis) measured after blood sample collection at screening and final visit/early termination visit 2.5. Treatment-emergent adverse events, i.e. all adverse events occurring or worsening after the application of the first medicated plaster, recorded during the whole study period | — |
Countries
Switzerland
Outcome results
None listed