Nicotine Pharmacokinetic and Pharmacodynamics Profile, Safety and Tolerability of P3L

A Single-center, Open-label, Ascending Nicotine Levels Study to Investigate the Nicotine Pharmacokinetic and Pharmacodynamics Profiles, Safety and Tolerability of P3L in Smoking Healthy Subjects in Relation to Nicorette® Inhalator

The purpose of this study is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD, i.e., subjective effects) profiles, and the safety and tolerability of the nicotine-containing aerosol delivered by Platform 3 Liquid (P3L) system at three different nicotine levels in smoking healthy subjects in relation to Nicorette® inhalator.

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: Nicorette® inhalator; Other: P3L

Detailed Description

The entire study will last between 16 to 49 days per subject. This includes :

• a screening period of up to 4 weeks prior to admission,
• 1 day of admission (Visit 2): after all inclusion/exclusion criteria are checked, all eligible subjects will be enrolled and perform a product test, first with P3L (at nicotine dose levels of approximately 50 μg/puff) and subsequently with Nicorette® inhalator (3 to 5 inhalations for each product).
• 4 days of on-site product use (one day with Nicorette® inhalator [Visit 3] and three days with P3L [Visit 4, Visit 5 and Visit 6]),
• 1 to 3 days between each product use and
• a 7-day safety follow-up period (discharge + 7 days), during which there are no scheduled investigational visits, and during which adverse events (AEs) and serious adverse events (SAEs) can be spontaneously reported by the subjects and the follow-up of AEs/SAEs will be conducted by the study investigational site.

Subjects will come to the investigational site the night before each assessment day, at least 12 hours prior to the product use, on Visit 4, Visit 5, and Visit 6. Subjects will stay overnight at the investigational site between the admission visit (Visit 2) and Visit 3. Smoking or use of any tobacco/nicotine-containing products or electronic cigarettes, apart from product use assigned on the assessment days, will not be allowed during their stay at the investigational site. Smoking will be allowed once the subjects have left the investigational site.

The maximum concentration of nicotine (Cmax) and the area under the concentration-time curve from start of product use to the last quantifiable time point (AUC0-last) will be derived from multiple blood sampling pre- and post-product use, and corrected for baseline nicotine concentration.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust Ltd (CCST)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is Caucasian
• Smoking, healthy subject as judged by the Investigator
• Subject smoked at least 10 commercially available non-menthol cigarettes (CCs) per day for the last 4 weeks
• Subject has smoked for at least the last 3 years prior to screening
• Subject does not plan to quit smoking in the next 3 months

Exclusion Criteria:

• As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason)
• Subject has donated or been in receipt of whole blood or blood products within 3 months prior to Admission Visit
• Female subject is pregnant or breast feeding
• Female subject does not agree to use an acceptable method of effective contraception
• Female subject uses estrogen-containing hormonal contraception or hormone replacement therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nicorette® inhalator then P3L; Each subject will use the Nicorette® inhalator (15 mg) on Visit 3, and then use the P3L aerosol at nicotine dose levels of approximately 50 µg/puff, 80 µg/puff and 150 µg/puff on Visits 4, 5 and 6, respectively.

Other: Nicorette® inhalator; Subjects will inhale the Nicorette® inhalator (15 mg) at the rate of one deep inhalation every 15 seconds on average, over approximately 20 minutes (80 inhalations in total).; Other: P3L; Subjects will inhale P3L (50 µg/puff, 80 µg/puff and 150 µg/puff) at the rate of one inhalation every 30 seconds on average, over approximately 6 minutes (i.e., 12 inhalations in total).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Nicotine Following Single Use of Nicorette® Inhalator	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Maximum Concentration (Cmax) of Nicotine Following Single Use of P3L 50 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Maximum Concentration (Cmax) of Nicotine Following Single Use of P3L 80 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Maximum Concentration (Cmax) of Nicotine Following Single Use of P3L 150 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of Nicorette® Inhalator	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use).	Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of P3L 50 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use).	Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of P3L 80 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use).	Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of P3L 150 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use).	Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of Nicorette® Inhalator	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of P3L 50 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of P3L 80 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of P3L 150 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of Nicorette® Inhalator	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of P3L 50 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of P3L 80 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0.
Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of P3L 150 µg/Puff	T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided.	Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0.

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Chris Wynne, MD, Christchurch Clinical Studies Trust Ltd (CCST)

Publications and helpful links

General Publications

• Teichert A, Brossard P, Felber Medlin L, Sandalic L, Franzon M, Wynne C, Laugesen M, Ludicke F. Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System. Nicotine Tob Res. 2018 Mar 6;20(4):458-465. doi: 10.1093/ntr/ntx093.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: August 21, 2015
• First Submitted That Met QC Criteria: August 24, 2015
• First Posted (Estimate): August 25, 2015

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Nicorette; nicotine absorption; nicotine containing product; adult smoker; nicotine delivery system
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: P3L-PK-01-NZ (Other Identifier: Philip Morris Products S.A)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No