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Drug Res (Stuttg) 2017; 67(02): 119-126
DOI: 10.1055/s-0042-118861
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Skin Irritation and Sensitization Potential of Fixed-Dose Combination of Diclofenac 1% and Menthol 3% Topical Gel: Results of Two Phase I Patch Studies

Dongzhou Jeffery Liu
1   Clinical Development, GSK, Collegeville, PA, USA
,
Agron Collaku
2   Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA
,
Jonathan S. Dosik
3   TKL Research Inc., Fair Lawn, NJ, USA
› Author Affiliations
Further Information

Publication History

received 17 June 2016

accepted 10 October 2016

Publication Date:
25 November 2016 (online)

Also available at
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Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

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.

Key words

skin pharmacology - analgesic drugs - drug research
 

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