title: Skin Irritation and Sensitization Potential of Fixed-Dose Combination of Diclofenac 1% and Menthol 3% Topical Gel: Results of Two Phase I Patch Studies.
abstract: Phase I, randomized, controlled patch studies were conducted to evaluate skin sensitization and irritation potential of a new gel formulation containing 1% diclofenac and 3% menthol as a fixed-combination product.In study A, healthy volunteers were exposed to 4 test patches containing 1% diclofenac+3% menthol, diclofenac, menthol, or placebo gels during an induction (nine 48 to 72-h applications) and challenge phase (one 48-h application). Some subjects were re-challenged to evaluate suspected sensitization. Study B participants underwent 21 consecutive 24-h patch applications of the 4 treatments from study A, 0.2% sodium lauryl sulfate (positive control), 0.9% saline, and a marketed gel (1% diclofenac, Voltaren). Application sites were visually scored by blinded observers for skin sensitization/irritation.In study A, 77% of participants showed minimal erythema and signs of glazing and peeling with 1% diclofenac+3% menthol by the end of the induction phase, which diminished during the challenge phase. Similar patterns were seen with menthol gel. Only 1 subject exhibited possible sensitization to 1% diclofenac+3% menthol. In study B, mean cumulative irritation score with 1% diclofenac+3% menthol was significantly higher (P<0.0001) vs. reference treatments; however, the positive control failed to produce the expected level of irritation. No treatment-related adverse events were reported.The sensitization and irritation potential of 1% diclofenac+3% menthol was greater than with the reference treatments. Comparison with positive control was not possible because it did not produce irritation under semiocclusive patch conditions.
authors.affiliation: Clinical Development, GSK, Collegeville, PA, USA.
authors.forename: Dongzhou Jeffery
authors.initials: DJ
authors.lastname: Liu
authors.affiliation: Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA.
authors.forename: Agron
authors.initials: A
authors.lastname: Collaku
authors.affiliation: TKL Research Inc., Fair Lawn, NJ, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dosik
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D000982:Antipruritics / Q000008:administration & dosage / Q000009:adverse effects; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D017453:Dermatitis, Irritant / Q000209:etiology*; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects*; D004338:Drug Combinations; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008610:Menthol / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D012867:Skin / Q000187:drug effects*; D057968:Transdermal Patch / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000982:Antipruritics; D004338:Drug Combinations; D005782:Gels; D004008:Diclofenac; D008610:Menthol