Design: Single center, open, repeated-dose, maximum use tolerance study in 62 healthy volunteers over 28 days.
Methodology: Diclofenac sodium 4% Spray Gel (DicloFlex®) was administered (5 sprays/application) to one knee 4 times daily for a period of 28 consecutive days. The intervals of application were approximately 6 hours. All adverse events were recorded beginning from the time the volunteer first received Diclofenac sodium 4% Spray Gel (DicloFlex®) . At day 7, day 14, day 21 and day 28 of application. A trained dermatological assessor examined the application area of all volunteers and indicated all application site reaction. Subjects who reported a side effect or were observed to have an application site reaction were assessed to determine suitability to continue with the study.
Results: Diclofenac sodium 4% Spray Gel (DicloFlex®) when applied 4 times daily over a period of 28 consecutive days in humans is well tolerated.
Design: Single centre, placebo-controlled, randomized, blinded, multiple dose study in 32 healthy volunteers.
Methodology: Once daily administration of Diclofenac sodium 4% Spray Gel (DicloFlex®) in comparison to Arthricare Cream, Speed Stick Deodorant, Diclofenac sodium 4% Spray Gel (DicloFlex®) placebo Spray, positive control Sodium Lauryl Sulfate and negative control Saline. Application forms for each individual and each formulation was occluded, semi occluded, and non-occluded.
Results: Under occluded condition Diclofenac sodium 4% Spray Gel (DicloFlex®) was less irritating, and required a longer time to cause irritation than Arthricare Cream, Speed Stick Deodorant and positive control Sodium Lauryl Sulfate. Diclofenac sodium 4% Spray Gel (DicloFlex®) required a longer time to cause irritation compared to the vehicle control. Under semi-occluded conditions, Diclofenac sodium 4% Spray Gel (DicloFlex®) was much less irritating than Arthricare Cream and Speed Stick Deodorant. Its irritation profile is similar to the negative control Saline (applied under occluded conditions). When applied unoccluded, Diclofenac sodium 4% Spray Gel (DicloFlex®) did not cause irritation.
Design: single centre, randomized, blinded study with 3 treatment-periods vs. vehicle in 205 healthy volunteers over 22 days.
Methodology: During the first period (Induction Phase) of 22 days patches with Diclofenac sodium 4% Spray Gel (DicloFlex®) were applied 3 times for 48 consecutive hours respectively and for 72 consecutive hours if over a weekend to the same administration-site. During the second period, of 10 -14 days no applications were made. During the third period (Challenge Phase ) a patch with Diclofenac sodium 4% Spray Gel (DicloFlex®) was applied to a previously untreated site for 48 consecutive hours. 48 hours after the last patch removal dermal reactions were measured.
Results: Diclofenac sodium 4% Spray Gel (DicloFlex®) and/or vehicle was associated with a confirmed sensitization rate of 0,5%. According to a recent review article (Wikinson et al., 2002), sensitization rates of under 1% are common among consumer products, and are "normally regarded as acceptable."
Design: randomised, double blind, placebo-controlled, 3-way crossover study with 51 subjects, over 15 days, Naproxen was used as positive control.
Methodology: Gastro-duodenal injury was assessed endoscopically at baseline and 90 min after the final treatment dose when mucosal biopsy samples were taken for vortex-stimulated PGE2 synthesis, measured by enzyme immunoassay. Whole blood COX-1/COX-2 activity was assessed at baseline and the end of the study by measuring ex vivo platelet thromboxane (TX) B2 and lipopolysaccharide stimulated PGE2, assayed similarly.
Results: Diclofenac sodium 4% Spray Gel (DicloFlex®) had no effect on gastric mucosal prostaglandin synthesis and does not cause gastric lesions, while both Naproxen and Celecoxib significantly reduced prostaglandin synthesis (compared to placebo). Naproxen significantly inhibited both COX-1 and COX-2 activity in blood, and Celecoxib inhibited COX-2 activity. Diclofenac sodium 4% Spray Gel (DicloFlex®) did neither inhibit COX-1 nor COX-2 activity. Naproxen significantly increased the number of gastric erosions compared to placebo, but Diclofenac sodium 4% Spray Gel (DicloFlex®) nor Celecoxib had a significant effect on gastric erosions.