Diclofenac sodium 4% Spray Gel (DicloFlex®) safety information

Long-term-tolerability (28 days) of Diclofenac sodium 4% Spray Gel (DicloFlex®) in healthy volunteers n=62

Diclofenac sodium 4% Spray Gel (DicloFlex®) was well tolerated, all symptoms were rated mild and only probably related to study drug
Only 2/62 discontinued the study due to dermal reactions

Long term tolerability of DSG 4% in healthy volunteers, data on file, TD0406

 

Induction phase Tolerance of Diclofenac sodium 4% Spray Gel (DicloFlex®) in repeated inhibitory patch test (RIPT) in humans vs. vehicle (n=205, 22 days)

Diclofenac sodium 4% Spray Gel (DicloFlex®) is better tolerated than the vehicle in the induction phase

Sensitization potential of DSG 4% and its vehicle in human, repeated insult patch test, TD0408

 

Challenge Phase Tolerance of Diclofenac sodium 4% Spray Gel (DicloFlex®) in repeated inhibitory patch test (RIPT) in humans vs. vehicle (n=205)

Diclofenac sodium 4% Spray Gel (DicloFlex®) is better tolerated than the vehicle in the challenge phase

Sensitization potential of DSG 4% and its vehicle in human, repeated insult patch test, TD0408

 

Inhibition of COX-2 activity Safety of Diclofenac sodium 4% Spray Gel (DicloFlex®) vs. Plabeco, Celecoxib and Naproxen on gastric prostaglandin synthesis (n=51)

Diclofenac sodium 4% Spray Gel (DicloFlex®) has no significant effect on gastric COX-2 activity and is comparable to placebo

Effect of DSG 4% applied to one knee on gastric prostaglandine synthesis compared to oral Celecoxib and placebo, TD0401

 

Effect on gastric PGE2 Synthesis Diclofenac sodium 4% Spray Gel (DicloFlex®) vs. Plabeco, Celecoxib and Naproxen on gastric prostaglandin synthesis (n=51)

Diclofenac sodium 4% Spray Gel (DicloFlex®) has no significant effect on gastric PGE2 Synthesis

Effect of DSG 4% applied to one knee on gastric prostaglandine synthesis compared to oral Celecoxib and placebo, TD0401

 

Long-term-tolerability in healthy volunteers

Design

Single center, open, repeated-dose, maximum use tolerance study in 62 healthy volunteers over 28 days

Methodology

DDSG 4% 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 DDSG 4% . 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

DDSG 4% when applied 4 times daily over a period of 28 consecutive days in humans is well tolerated

Long term tolerability of DSG 4% in healthy volunteers, data on file, TD0406

21-day cumulative irritation study of DDSG 4% in humans vs. Arthricare, Speed Stick deodorant and placebo

Design

Single centre, placebo-controlled, randomized, blinded, multiple dose study in 32 healthy volunteers

Methodology

Once daily administration of DDSG 4% in comparison to Arthricare Cream, Speed Stick Deodorant, DDSG 4% 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 DDSG 4% was less irritating, and required a longer time to cause irritation than Arthricare Cream, Speed Stick Deodorant and positive control Sodium Lauryl Sulfate. DDSG 4% required a longer time to cause irritation compared to the vehicle control. Under semi-occluded conditions, DDSG 4% 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, DDSG 4% did not cause irritation.

21-day cumulative irritation study of DSG 4% in humans, TD0409

Repeated inhibitory patch test (RIPT) in humans of DDSG 4% vs. vehicle

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 DDSG 4% 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 DDSG 4% was applied to a previously untreated site for 48 consecutive hours. 48 hours after the last patch removal dermal reactions were measured.

Results

DDSG 4% 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."

Sensitization potential of DSG 4% and its vehicle in human, repeated insult patch test, TD0408

Repeated inhibitory patch test (RIPT) in humans of DDSG 4% vs. vehicle

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 DDSG 4% 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 DDSG 4% was applied to a previously untreated site for 48 consecutive hours. 48 hours after the last patch removal dermal reactions were measured.

Results

DDSG 4% 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."

Sensitization potential of DSG 4% and its vehicle in human, repeated insult patch test, TD0408

Effect of DDSG 4% on gastric Prostaglandine synthesis vs. Celecoxib, Naproxen and Plabeco

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

DDSG 4% 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. DDSG 4% did neither inhibit COX-1 nor COX-2 activity. Naproxen significantly increased the number of gastric erosions compared to placebo, but DDSG 4% nor Celecoxib had a significant effect on gastric erosions.

Effect of DSG 4% applied to one knee on gastric prostaglandine synthesis compared to oral Celecoxib and placebo, TD0401