Comparative bioavailability of diclofenac epolamine tablets vs. Flector® granules for oral solution in healthy volunteers, pilot study in fed conditions

INTERVENTION: Test product (T): Diclofenac epolamine (DHEP) 50 mg soluble tablets containing 65 mg of diclofenac epolamine corresponding to 50 mg of diclofenac sodium Reference therapy (R): Flector® granules for oral solution, 50 mg sachets containing 65 mg of diclofenac epolamine corresponding to 50 mg of diclofenac sodium A single dose of T and R was administered to healthy male volunteers under fed conditions according to a randomised two‐way cross‐over design, with a wash‐out interval of at least 5 days between consecutive administrations. The subjects were assigned to one sequence of treatments (TR or RT) according to the randomisation list and the cross‐over design. The subjects were randomised to receive one of the two treatments (i.e. either T or R) during period 1 and the other treatment during period 2. The concentration of diclofenamic free acid in plasma was measured at the following time‐points: pre‐dose (0) and 3, 9, 15, 21, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6 and 8 h post‐dose. CONDITION: Diclofenac epolamine (DHEP) 50 mg soluble tablets containing 65 mg of diclofenac epolamine corresponding to 50 mg of diclofenac sodium ; Not Applicable PRIMARY OUTCOME: Rate (Cmax) and extent (AUC0‐t) of absorption of diclofenamic acid: the concentration of diclofenamic free acid in plasma was measured at the following time‐points: pre‐dose (0) and 3, 9, 15, 21, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6 and 8 h post‐dose SECONDARY OUTCOME: 1. Pharmacokinetic (PK) profile of diclofenamic acid: the concentration of diclofenamic free acid in plasma was measured at the following time‐points: pre‐dose (0) and 3, 9, 15, 21, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6 and 8 h post‐dose; 2. Safety and tolerability of diclofenamic acid:; 2.1. Record of adverse events: AEs assessed throughout the study; 2.2. Vital signs: subjects' blood pressure (BP) and heart rate (HR) measured by the investigator or his/her deputy after 5 min at rest in sitting position at: screening visit, day 1 of each period: pre‐dose (0) and 8 h post‐dose, ETV. The check on day 1, 8 h post‐dose of period 2, also corresponded to the final assessment; 2.3. Electrocardiograms: a 12‐lead resting ECG performed and interpreted by the investigator at the screening and final visit; 2.4. Physical examination, performed at screening and at final visit. Body weight (BW) recorded at screening and at final visit. Subjects weighed (kg) lightly clothed without shoes; 2.5. Height and Body Mass Index (BMI) recorded at screening visit. BMI calculated as weight [kg] / (height [m] squared); 2.6. Laboratory analysis: routine haematology, blood chemistry and urinalysis laboratory tests performed under fasting conditions at screening; 2.7. A urine drug test performed using a urine multi‐drug kit at screening. The following drugs assessed: cocaine, amphetamine, methamphetamine, cannabinoids (delta‐9‐tetrahydrocannabinol ‐ THC), opiates and ecstasy. The same analyses, with the exception of drug screening and virology, performed at the final visit INCLUSION CRITERIA: 1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and age: males, 18‐55 year 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 50‐90 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