Tolerability and bioavailability of a new DHEP medicated plaster versus a market reference formulation on healthy subjects Not Applicable
Conditions
Interventions
The first screening visit takes place between Day -21 and Day -2.
One (1) DHEP medicated plaster (T1: 360mg/140cm²
T2: 180mg/140cm²
R: 182mg/140cm²) is applied once a day (o.d.) for 2 consecutive days in 3 study periods according to a 3-way cross-over randomised Williams design.
The sequence of Investigational Medi
1 = mild
2 = mode
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: 18.5-30 kg/m2 inclusive 4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 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 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 screeningvisit; 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 ECG in 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: history of clinically significant 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 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 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 |
|---|---|
| 1. Local tolerability of diclofenac is evaluated as adverse drug reactions (ADRs) at the application site measured after application for 2 consecutive days, including: 1.1. Application site erythema, dryness, swelling and exfoliationass essed by the investigator using a 4-grade scale 1.2. All other treatment-related AEs occurring at the application site, spontaneously reported by the subjects or observed by the investigator | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic (PK) profile of diclofenac in plasma after o.d. application for 2 consecutive days. PK profile will be evaluated using a fully validated method Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method, with a lower quantification limit of 1 ng/ml, on blood samples taken on Day 1: pre-dose (0) and Days 2-3: Day 2 at pre-dose (0) and 1, 2, 3, 4, 6, 8, 10, 12, 16 and Day 3 at 24 h post-dose (12 samples in each study period) 2. Collection of safety data of the study products assessed during the study by the number of adverse events (AEs) reported through the study duration and measured using: 2.1. Blood and urine samples for haematology, blood chemistry, and urine analysis at the screening visit and final visit/ETV 2.2. Body weight (kg) at the screening visit and final visit/ETV and height at the screening visit to calculate Body Mass Index (BMI) at the screening visit and final visit/ETV 2.3. Vital signs (blood pressure [mmHg], heart rate [bpm]) at the screening visit, in each study period on Day -1 and on Day 3, 24 h post-application and at ETV (ifv applicable) 2.4. ECG measured using 12-Lead electrocardiogram at the screening visit | — |
Countries
Italy, Switzerland
Outcome results
None listed