Studio per valutare l’adesività di Flectoparin® Tissugel dopo applicazione del cerotto in soggetti sani

The study consists of a screening visit, a treatment phase of one study period and a final visit/early termination visit (ETV).
For each subject, two DHEP-Heparin medicated plasters are applied concurrently as follows: one plaster without reinforcement (PW) and one plaster with reinforcement (PR) are applied to the right and left side of the upper back (dorsal region, below the scapula), with the longer side parallel to the spine, at the same height, as near as possible to the spine. Plaster for PR treatment was reinforced using small pieces of tape applied to the four corners of the DHEP-Heparin plaster.

The investigator assesses each plaster adhesion at 4, 8, 12, 16, 20 and 24 h post-application using the following 5-point scale, according to the FDA Guidance for Assessing adhesion.

In addition, at each time point, when adhesion was assessed on the 5-point scale, the actual percentage adherence value (%) was estimated by the investigator and reported in the CRF.

The two assessments (score and actual percentage evaluation) are visually performed by a an experienced and trained scorer (the Principal Investigator) who was previously involved as investigator in several clinical trials where visual evaluation of patch detached area was part of study assessments.

Standardised digital photographs are taken before application and at each assessment time for each plaster.

After adhesion assessment and photograph, at each assessment time the shapes of attachment/detachment area of each plaster were traced on an acetate sheet in order to collect an additional image of the detached area of each plaster.

Each plaster contained 181 mg DHEP corresponding to 140 mg diclofenac sodium. Therefore, the subjects are exposed to a total dose of approximately 280 mg diclofenac sodium.

The randomisation list is computer-generated by the Department of Biometry at the Contract Research Organization (CRO) using the PLAN procedure of the validated SAS for Windows Version 9.1.3 Serv

Inclusion criteria: 1. Informed consent: signed written informed consent before inclusion in the study
2. Sex and Age: males/females, 18-55 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: 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 (females only): females 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 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 agreed to use a male condom with spermicide
6.4. A sterile sexual partner
Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year are admitted. For all female subjects, pregnancy test result had to be negative at screening and at each scheduled evaluation.

Exclusion criteria: 1. Electrocardiogram (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. 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 considered could affect the outcome of the study
5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that could interfere with the aim of the study
6. Application site: diseased-skin, skin wounds or open injuries at the applications site
7. Medications: medications, including over the counter medications and herbal remedies for 2 weeks before the start of the study. Hormonal contraceptives for females were allowed
8. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval was 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. 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], caffeine (>5 cups coffee/tea/day) or tobacco abuse (?10 cigarettes/day)
10. Drug test: positive result at the drug test at screening
11. Alcohol test: positive alcohol breath test at day -1
12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
13. Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women