Adhesion study of Flectoparin® Tissugel following plaster application

INTERVENTION: 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 CONDITION: DHEP‐medicated plaster ; Skin and Connective Tissue Diseases ; DHEP‐medicated plaster PRIMARY OUTCOME: Adhesion score for the investigational plaster without reinforcement (PW) is measured the 5‐point scale at 4, 8, 12, 16, 20 and 24 h post‐application. SECONDARY OUTCOME: Safety and general tolerability of the IMP were based on the following assessments:; Record of adverse events ; Adverse events (AEs) were assessed throughout the study.; ; Vital signs ; Subjects’ blood pressure and heart rate were measured by the investigator or his deputy after 5 min at rest in the sitting position at screening, on days 1‐2 at pre‐dose and 24 h post‐application, and in case of ETV. The vital signs measurement at 24 h post‐dose was considered as the final assessment.; ; Electrocardiograms; A 12‐lead resting ECG was performed in supine position at screening and interpreted by the investigator. ; ; Physical examination and body weight; A physical examination was performed at screening .Body weight, height and body mass index (BMI) were recorded at screening only. Subjects were weighed (kg) lightly clothed without shoes. BMI was calculated as weight [kg] / (height [m] squared).; ; Laboratory analysis; 1. Routine haematology, blood chemistry and urinalysis laboratory tests were performed, under fasting conditions, at screening. ; 2. Haematology: leukocytes and leukocyte differential count (percentage and absolute values), erythrocytes, haemoglobin (conv. units), haemoglobin (IS units), haematocrit, MCV, MCH, MCHC, thrombocytes.; ; Blood Chemistry: ; 1. Electrolytes: sodium, potassium, calcium, chloride, inorganic phosphorus; 2. Enzymes: alkaline phosphatase, ?‐GT, AST, ALT; 3. Substrates/metabolites: total bilirubin, creatinine, fasting glucose, urea, uric acid, total cholesterol, triglycerides; Proteins: total proteins; ; Serum pregnancy test (women only, at screening); ; Urine analysis: ; 1. Urine chemical analysis (stick): pH, specific weight, appearance, colour, nitrites, proteins, glucose, urobilinogen, bilirubin, ketones, haematic pigments, leukocytes; 2. Urine sediment (analysis performed only if positive): leukocytes, erythrocytes, flat cells, round cells, crystals, cylinders, mucus, bacteria; 3. Urine pregnancy test (women only, on day ‐1).; 4. erum virology: Hepatitis B (HBs antigen), Hepatitis C (HCV Antibodies), HIV 1/2 (HIV Ag/Ac combo). ; A urine drug test was performed at the clinical centre at screening, using a urine multi‐drug kit. The following drugs were assessed: cocaine, amphetamine, methamphetamine, cannabinoids (delta‐9‐tetrahydrocannabinol ‐ THC), opiates and ecstasy. ; ; Measurements of Primary and secondary variables; Primary variables:; Adhesion scores on a 5‐point numerical scale (13), where score 0==90% adhered (essentially no lift off the skin), score 1==75% to <90% adhered (some edges only lifting off the skin), score 2==50% to <75% (less than half of the plaster lifting off the skin), score 3=>0% to <50% adhered (not detached, but more than half of the plaster lifting off the skin without falling off), score 4=0% adhered (plaster detached; completely off the skin) for PW.; ; Secondary variables: ; 1. Adhesion scores on the 5‐point numerical scale, as detailed above, for PR application.; 2. Assessment of plaster adherence as a percentage of total plaster area for both PW and PR application; 3. Safety variables: treatment‐emergent adverse events, vital signs (blood pressure, heart rate), laboratory parameters 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 spermici