Pharmacokinetics and Comparative Bioavailability of Nicotine From Two Variants of NP2, NP2-4mg and NP2-6mg, Compared to Nicotine Lozenge 4mg (Loz-4mg) and Nicotine Gum 4mg (Gum-4mg)

NCT06171490 | Completed

• 1 other identifier: PZ-PK-03-CAN
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

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).

Conditions

Tobacco Use

Keywords

Nicotine; Nicotine-containing products; Tobacco; Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration [Cmax]

  To measure Cmax following use of the investigational products and reference products

  Measured from start of product use to 24 hours

• 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]

  To measure the area under the background-corrected concentration-time curve (AUC) from start of product use

  Measured from start of product use (T0) to 2 minutes, to 4 minutes, to 10 hours, to time of last quantifiable concentration.

• Ratio of [AUC0-last] and [AUC0-infinity]

  To measure the ratio of \[AUC0-last\] and \[AUC0-infinity\]

  Measured from start of product use to 24 hours

• Time to the observed maximum concentration [Tmax]

  To measure the maximum ratio of background-corrected concentration over time, from T0 (excluded) to Tmax (included)

  Measured from start of product use to 24 hours

• Elimination rate constant [kel]

  To measure the fraction of nicotine eliminated per unit of time, following use of the investigational products and reference products

  Measured from start of product use to 24 hours

• Half-life of nicotine [t1/2]

  To measure the half-life of nicotine, following use of the investigational products and reference products

  Measured from start of product use to 24 hours

Study Arms (4)

Product Sequence 1

ACTIVE COMPARATOR

From Day 1 to Day 4, after at least 23 hours of abstinence from any nicotine/tobacco containing products, subjects will use one of the four investigational products according to randomized product use sequence and as instructed by the investigational site personnel. The list of possible sequences are: NP2-4mg; NP2-6mg; Loz-4mg; Gum-4mg / NP2-6mg; Gum-4mg; NP2-4mg; Loz-4mg / Gum-4mg; Loz-4mg; NP2-6mg; NP2-4mg / Loz-4mg; NP2-4mg; Gum-4mg; NP2-6mg

Other: NP2-4mg; Other: NP2-6 mg; Other: Loz-4mg; Other: Gum-4mg

Product Sequence 2

ACTIVE COMPARATOR

From Day 1 to Day 4, after at least 23 hours of abstinence from any nicotine/tobacco containing products, subjects will use one of the four investigational products according to randomized product use sequence and as instructed by the investigational site personnel. The list of possible sequences are: NP2-4mg; NP2-6mg; Loz-4mg; Gum-4mg / NP2-6mg; Gum-4mg; NP2-4mg; Loz-4mg / Gum-4mg; Loz-4mg; NP2-6mg; NP2-4mg / Loz-4mg; NP2-4mg; Gum-4mg; NP2-6mg

Other: NP2-4mg; Other: NP2-6 mg; Other: Loz-4mg; Other: Gum-4mg

Product Sequence 3

ACTIVE COMPARATOR

From Day 1 to Day 4, after at least 23 hours of abstinence from any nicotine/tobacco containing products, subjects will use one of the four investigational products according to randomized product use sequence and as instructed by the investigational site personnel. The list of possible sequences are: NP2-4mg; NP2-6mg; Loz-4mg; Gum-4mg / NP2-6mg; Gum-4mg; NP2-4mg; Loz-4mg / Gum-4mg; Loz-4mg; NP2-6mg; NP2-4mg / Loz-4mg; NP2-4mg; Gum-4mg; NP2-6mg

Other: NP2-4mg; Other: NP2-6 mg; Other: Loz-4mg; Other: Gum-4mg

Product Sequence 4

ACTIVE COMPARATOR

From Day 1 to Day 4, after at least 23 hours of abstinence from any nicotine/tobacco containing products, subjects will use one of the four investigational products according to randomized product use sequence and as instructed by the investigational site personnel. The list of possible sequences are: NP2-4mg; NP2-6mg; Loz-4mg; Gum-4mg / NP2-6mg; Gum-4mg; NP2-4mg; Loz-4mg / Gum-4mg; Loz-4mg; NP2-6mg; NP2-4mg / Loz-4mg; NP2-4mg; Gum-4mg; NP2-6mg

Other: NP2-4mg; Other: NP2-6 mg; Other: Loz-4mg; Other: Gum-4mg

Interventions

NP2-4mg OTHER

NP2-4 mg is a new product containing tobacco-derived nicotine.

Product Sequence 1; Product Sequence 2; Product Sequence 3; Product Sequence 4

NP2-6 mg OTHER

NP2-6 mg is a new product containing tobacco-derived nicotine.

Product Sequence 1; Product Sequence 2; Product Sequence 3; Product Sequence 4

Loz-4mg OTHER

The Loz-4mg reference product is a commercially available 4mg nicotine lozenge.

Product Sequence 1; Product Sequence 2; Product Sequence 3; Product Sequence 4

Gum-4mg OTHER

The Gum-4mg reference product is a commercially available 4mg nicotine gum.

Product Sequence 1; Product Sequence 2; Product Sequence 3; Product Sequence 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• Subject previously attempted to quit using tobacco- or nicotine-containing products within 28 days prior to the first study product administration.
• Subject has donated plasma within seven days prior to Screening or has donated or lost 450 mL or more of whole blood within 8 weeks prior to Screening for males, and in the 12 weeks prior to Screening for females.
• Subject has a known sensitivity or allergy to any of the investigational products, or ingredients.
• Subject has a positive serology test for HIV 1/2, Hepatitis B, Hepatitis C.
• Subject has a history of alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (2)

Pharma Medica Research Inc.

Toronto, Ontario, M1S 3V6, Canada

Location

Syneos Health Clinique Inc.

Québec, G1P 0A2, Canada

Location

MeSH Terms

Conditions

Tobacco Use

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Christelle Haziza, PhD

  Philip Morris Products S.A.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a partially blinded study. The Investigator and subjects will be blinded to the randomized sequence and to the variants of the investigational product (IP). In contrast, the pharmacy staff will not be blinded to the randomized sequence and to the variants of the IP.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted with 4 periods and 4 sequences in a Williams design (crossover).

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 14, 2023
• Study Start: October 20, 2023
• Primary Completion: January 14, 2024
• Study Completion: March 20, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Locations

CA (2)