Clinical Studies
for Nicotine Products

Designed to understand the puffing use behavior when subjects use an electronic nicotine delivery device or heated tobacco product. Parameters such as puff volume, puff duration, peak airflow, and inter-puff intervals are measured to understand if the product is used differently from the standards used in the laboratory. The data from these studies can also be used in desk-based toxicological assessments as a more accurate “dose” can be determined to calculate the product's toxicological risk.

PK/PD studies are essential data points in regulatory applications. They provide information that indicates how much nicotine is delivered to the user by assessing the levels of nicotine in the blood compared to the levels detectable after smoking a combustible cigarette. Several PK parameters are considered for assessing the data and product.

PD data relies on validated satisfaction questionnaires. The product should demonstrate levels of satisfaction similar to a combustible cigarette to ensure that smokers can achieve sufficient satisfaction to off-ramp from using a conventional tobacco product.

These studies look at understanding the efficacy of a novel nicotine delivery product by analyzing changes in the blood, urine, and physiology. Biomarkers of Exposure (BoE) are generally metabolic products of the Harmful and Potentially Harmful Constituents (HPHCs) found in cigarette smoke. Since the laboratory analysis likely shows a reduction or elimination of the HPHCs compared to combustible cigarettes, BoE Studies look to provide clinical confirmation that exposure to HPHCs is reduced. 

BoE studies can either be conducted over a short duration (5 days) when subjects stay in a clinic and their exposures to other sources of the HPHCs are controlled or be longer ambulatory studies (up to 6 months) where subjects use the product at home in the real world. The most robust applications use a combination of both approaches to show the reductions in both controlled and uncontrolled environments.

BoPH are associated with smoking-related disease endpoints such as lung function, blood pressure, and inflammation. These studies are designed to show that prolonged use of the novel nicotine delivery product instead of combustible cigarettes results in changes in these biomarkers, indicating a reduction in the risk of disease development. 

BoPH studies usually last 12-18 months, as these biomarkers need a more extended period to demonstrate change because of stopping or reducing smoking combustible cigarettes. These types of studies are typically only required for MRTP applications.