A Randomized, Controlled Study to Assess Biomarkers of Exposure in Adult Smokers Switching to Oral Nicotine Products

This open‐label, randomized, controlled, in‐clinic, 6‐parallel‐group study evaluated changes in biomarkers of exposure (BoEs) to select harmful and potentially harmful constituents in adult smokers (N = 213) not planning to quit smoking. Adult smokers were randomized to continue smoking (CS), reduce smoking by 50% and dual use oral tobacco‐derived nicotine (OTDN) products (VERVE chews/discs), stop smoking and exclusively use discs or chews, or stop using all tobacco products (NT). The primary objective compared 24‐hour urinary total 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL; a biomarker for the carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone) in dual and exclusive use of discs and chews to continue smoking and NT on day 7. NNAL levels on day 7 were significantly lower (P < .05) among dual and exclusive users of discs/chews compared to continue smoking; median percent reductions were ≈30% and ≈73%, respectively. NNAL levels were not significantly different between those who used discs/chews and the NT group. Many of the additional secondary biomarkers of exposure were significantly lower in dual users (10/19) and exclusive users of discs/chews (17/19) compared to the continue smoking group. Overall, reductions in secondary biomarkers of exposure were greater in exclusive users than dual users. The 24‐hour urinary nicotine equivalents were significantly lower (P < .05) among exclusive users of discs/chews compared to continue smoking. The discs/chews appeared to be well tolerated. These results demonstrate that while switching completely to discs/chews substantially reduces exposure to select harmful and potentially harmful constituents, dual use with 50% reduction in cigarette consumption also reduces exposure. oral tobacco‐derived nicotine products like discs/chews may present a harm reduction opportunity for adult smokers, particularly those not intending to quit smoking.