A Multi-center, Randomized, Controlled, Partially Blinded Study to Assess the Pharmacokinetics and Comparative Bioavailability of Nicotine From Two Variants of Nicotine Pouch 2.0 (NP2), 4mg and 6mg, Compared to Nicotine Lozenge 4mg and Nicotine Gum 4mg in Adult Cigarette Smokers
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Tobacco Use
- Sponsor
- Philip Morris Products S.A.
- Enrollment
- 56
- Locations
- 2
- Primary Endpoint
- Time to the observed maximum concentration [Tmax]
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multi-center, randomized, controlled, partially blinded study to assess the pharmacokinetics and comparative bioavailability of nicotine from two variants of NP2 (4 and 6 mg) in comparison with Loz-4mg and Gum-4mg in adult cigarette smokers. The subjects will be blinded to the randomized sequence and will be blinded to the variants of NP2 they will receive. The study will be conducted with 4 periods and 4 sequences in a Williams design (crossover).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has signed the ICF and is able to understand the information provided in the ICF.
- •Subject has smoked on a daily basis for at least the last 18 months prior to the Screening visit.
- •Subject has smoked on average ≥10 commercially available regular CIG/day over the last 4 weeks. Smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL).
- •Subject is healthy as judged by the Investigator based on available assessments from the screening period (e.g., safety laboratory, spirometry, vital signs, physical examination, ECG, and medical history).
Exclusion Criteria
- •Subject has reasons other than medical (e.g., psychological, social reason) not to be part of the study, as determined by the Investigator.
- •Subject is legally incompetent, or physically or mentally incapable of giving consent (e.g., emergency situation, under guardianship, prisoners).
- •Subject has a clinically relevant disease which requires medication or any other medical condition including abnormal spirometry, safety laboratory, as determined by the Investigator.
- •Subject presents difficulty with venipuncture and/or poor venous access.
- •Subject has an oromucosal or dental condition, which may affect the use of the investigational products, as determined by the Investigator or subject has orthodontic braces and retention wire (could likely interfere with the gum dosing).
- •Subject has medical conditions which require, or will require during the study, a medical intervention (e.g., start of treatment, surgery, hospitalization).
- •Presence of fever (body temperature \>37.5°C) (e.g., a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to dosing.
- •Subject has a Hemoglobin level \< 11.0 g/dL for females and \< 12.0 g/dL for males at the Screening.
- •Subject uses medication or any substance that aids in smoking cessation.
- •Subject postponed the decision to quit using tobaccoor nicotine-containing products in order to participate in this study.
Outcomes
Primary Outcomes
Time to the observed maximum concentration [Tmax]
Time Frame: Measured from start of product use to 24 hours
To measure the maximum ratio of background-corrected concentration over time, from T0 (excluded) to Tmax (included)
Area under the observed concentration-time curve (AUC) from start of product use (T0) to timepoint of last quantifiable concentration [AUC0-last] and extrapolated to infinity [AUC0-infinity]
Time Frame: Measured from start of product use (T0) to 2 minutes, to 4 minutes, to 10 hours, to time of last quantifiable concentration.
To measure the area under the background-corrected concentration-time curve (AUC) from start of product use
Half-life of nicotine [t1/2]
Time Frame: Measured from start of product use to 24 hours
To measure the half-life of nicotine, following use of the investigational products and reference products
Elimination rate constant [kel]
Time Frame: Measured from start of product use to 24 hours
To measure the fraction of nicotine eliminated per unit of time, following use of the investigational products and reference products
Maximum Plasma Concentration [Cmax]
Time Frame: Measured from start of product use to 24 hours
To measure Cmax following use of the investigational products and reference products
Ratio of [AUC0-last] and [AUC0-infinity]
Time Frame: Measured from start of product use to 24 hours
To measure the ratio of \[AUC0-last\] and \[AUC0-infinity\]