Clinical trial design to study the effects of pharmacological intervention on different models of skin pain and inflammation – methodology and first results

Skin photodamage due to excessive ultraviolet (UV) light exposure is followed by a series of biochemical and immunologic events that cause inflammation including the release of prostaglandins, lipoxygenase products, cytokines (e.g. tumour necrosis factor-α), adhesion molecule, reactive oxygen radicals and mast cell-derived mediators, such as histamine and tryptase. In various inflammatory pain conditions, including UVB sunburn, nociceptors are sensitized to mechanical and thermal stimuli at the site of inflammation. This phenomenon, which leads to hyperalgesia, can be used to investigate pharmacological effects of different drugs and drug formulations in the model of UVB-induced skin inflammation. Two additional models are useful for evaluating the direct, prostaglandin-independent, modulatory effects on neuronal excitability of nociceptors (chemosensitivity): the chemically induced pain (capsaicin test) and itch (histamine test). IDEA-070 is a novel carrier-based topical dosage form of an analgesic drug that acts by inhibiting cyclooxygenase (COX-1 and COX-2) and lipoxygenase, thereby reducing prostaglandin- and leukotriene-mediated inflammatory reactions. We used all three described models in the framework of a phase I clinical study to assess efficacy of IDEA-070. The results of an interim analysis of the UVB model from the first 12 healthy volunteers indicate that IDEA-070 as well as hydrocortisone-21-acetate (HC) reduces the UVB-induced heat hyperalgesia if applied immediately after UV exposure. In contrast, only IDEA-070 is effective when used 6 h after exposure to UVB. In addition, IDEA-070, but not HC, suppressed erythema development if used immediately after UVB exposure as well as 6 h after UVB irradiation.