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)

Tobacco Use Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06171490
• Other study ID #: PZ-PK-03-CAN
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 20, 2023
• Est. completion date: July 31, 2024

Study information

• Verified date: February 2024
• Source: Philip Morris Products S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 56
• Est. completion date: July 31, 2024
• Est. primary completion date: January 14, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.
• 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%).
• Subject has a positive urine drug test. Investigator will assess whether THC positive subjects are eligible for participation in the study.
• Subject has a positive alcohol breath test.
• Subject or one of their family members is a current or former employee of the tobacco industry.
• Subject or one of their family members a is an employee of the investigational site or of any other parties involved in the study.
• Subject has participated in another clinical study within 30 days prior to the Screening Visit or concomitantly participates in an investigational study involving no drug or device administration.
• Subject has been previously screened or enrolled in this study (except alternate subjects).
• For women only: subject is pregnant (does not have negative pregnancy tests at Screening Visit and at Admission) or is a lactating female.
• For women of childbearing potential only: subject does not agree to use an acceptable method of effective contraception.

Related Conditions & MeSH terms

• Tobacco Use

Intervention

Other:
• NP2-4mg
NP2-4 mg is a new product containing tobacco-derived nicotine.
• NP2-6 mg
NP2-6 mg is a new product containing tobacco-derived nicotine.
• Loz-4mg
The Loz-4mg reference product is a commercially available 4mg nicotine lozenge.
• Gum-4mg
The Gum-4mg reference product is a commercially available 4mg nicotine gum.

Locations

Country	Name	City	State
Canada	Syneos Health Clinique Inc.	Québec
Canada	Pharma Medica Research Inc.	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Philip Morris Products S.A.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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.
Primary	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
Primary	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
Primary	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
Primary	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