Bioavailability and tolerability study of two new diclofenac epolamine lecithin gel formulations (2.6% and 3.9%) in comparison with the marketed diclofenac epolamine lecithin gel formulation 1.3% (Effigel® IBSA)

INTERVENTION: The study consisted of a screening visit, a treatment phase of three study periods separated by wash‐out intervals of at least 5 days between the start of the 2nd application of a period and the start of the 1st application of the following period, and a final visit/early termination visit. Test 1 (T1): DHEP 2.6% (corresponding to 2% of diclofenac sodium) gel, IBSA Institut Biochimique S.A.,Switzerland. Batch N. 160101, re‐test date JUL16 Test 2 (T2): DHEP 3.9% (corresponding to 3% of diclofenac sodium) gel, IBSA Institut Biochimique S.A.,Switzerland. Batch N. 160102, re‐test date JUL16 Reference (R): Effigel®, DHEP 1.3% (corresponding to 1% of diclofenac sodium) gel, IBSA Institut Biochimique S.A., Switzerland. Batch N. 150606, expiry date JUN18 Each subject received a total of 16 g of each IMP. The total dose was subdivided into two applications of 8 g each. Considering the dose regimen of up to four daily applications recommended for Effigel®, two daily applications of 8 g each were tested in the present study. Each dose of 8 g of gel was applied to the maximum application area (800 cm2) as recommended for Effigel®. CONDITION: Bioavailability and tolerability study of two new diclofenac epolamine lecithin gel formulations ; Not Applicable PRIMARY OUTCOME: Pharmacokinetic parameters (Cmax, AUC0‐t, AUC0‐8, t1/2, ?z and tmax) of plasma diclofenac free acid after two applications of T1, T2 and R. Plasma concentrations of diclofenac are measured at the following time‐points (13 samples in each study period):; 1. On day 1 at pre‐dose (0), i.e. before the start of the 1st application; 2. On day 2 at pre‐dose (0), i.e. 5 min before the start of the 2nd application, and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after the start of the 2nd application SECONDARY OUTCOME: 1. Treatment‐emergent adverse events; vital signs (blood pressure, heart rate); physical examinations and laboratory tests performed at screening and final visit/early termination visit; 2. Local tolerability, evaluated according to a 4‐grade score scale before the start and 2 h after the start of the 1st application and before the start and 4 and 12 h after the start of the 2nd application INCLUSION CRITERIA: 1. Signed written informed consent 2. Males/females, 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. 6. Contraception and fertility (women only): women of child‐bearing potential were required to use 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 c