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Photosensitizing potential of pradigastat in healthy subjects: a randomized controlled trial using three defined sunlight exposure conditions

Bauer, Daniel and Soon, Rachel and Kulmatycki, Kenneth and Chen, Yuming and Noe, Adele and Chen, Jin and Dosik, Jonathan and Meyers, Charles (2016) Photosensitizing potential of pradigastat in healthy subjects: a randomized controlled trial using three defined sunlight exposure conditions. Photochem. Photobiol. Sci., 15 (9). pp. 1155-1162. ISSN 1474-905X1474-9092

Abstract

Background: Pradigastat absorbs light within sunlight range (290-700 nm), and demonstrated a mild phototoxicity risk in preclinical studies. This clinical trial was conducted to assess a potential photosensitivity risk at the highest therapeutic dose in humans.
Methods: 47 healthy adults were randomized to Part A (double-blind, placebo-controlled; 3:1 pradigastat:placebo) or to Part B (open-label, investigator blind; ciprofloxacin as positive control). Three different irradiation conditions (1. full range UVB/UVA, 2. UVA only, 3. ½ MED from UVB/UVA + 16 J/cm2 UVA) were applied to simulate different environments. The photosensitizing potential of pradigastat versus placebo and ciprofloxacin was assessed by determining the minimum erythemal dose (MED) and calculating the photosensitivity index (PI) at 1 and 24 h post-irradiation. Secondary endpoints included the change from baseline in MED, and scoring of skin reactions.
Results: With UVA-only, no substantial changes in MED were observed for pradigastat and placebo groups. The PI remained relatively constant (from 10 min to 72 h) with a median value of 1.0. For ciprofloxacin, a considerable reduction in MED was noted from baseline at 24 h (-32%). The difference in mean PI between ciprofloxacin-pradigastat, and ciprofloxacin-placebo, was significant at 24 h (p<0.001). Following full UVB/UVA irradiation, a time-dependent reduction in MED was observed for all treatment groups; however PI differences between treatments were not significant. Erythema grading scores were comparable between pradigastat and placebo, whereas the number of ciprofloxacin-treated subjects experiencing Grade 2 erythema increased substantially.
Conclusion: Pradigastat does not induce photosensitivity reactions at doses up to 40 mg/day.

Item Type: Article
Keywords: Pradigastat, LCQ908, photosensitivity, photosafety, phototoxicity
Date Deposited: 13 Oct 2016 00:45
Last Modified: 13 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/24109

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