Nicotine Pharmacokinetic and Pharmacodynamics Profile, Safety and Tolerability of P3L

NCT02532374 | Completed Results

• 1 other identifier: P3L-PK-01-NZ
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Smoking

Keywords

nicotine absorption; nicotine containing product; adult smoker; Nicorette; nicotine delivery system

Outcome Measures

Primary Outcomes (16)

• 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.

Study Arms (1)

Nicorette® inhalator then P3L

EXPERIMENTAL

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; Other: P3L

Interventions

Nicorette® inhalator OTHER

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).

Nicorette® inhalator then P3L

P3L OTHER

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).

Nicorette® inhalator then P3L

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (1)

Christchurch Clinical Studies Trust Ltd (CCST)

Christchurch, 8011, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 28482017 RESULT

MeSH Terms

Conditions

Smoking

Condition Hierarchy (Ancestors)

Behavior

Results Point of Contact

• Title: Loyse Felber Medlin
• Organization: Philip Morris Products S.A.

Loyse.FelberMedlin@pmi.com

+41 (58) 242 2686

Study Officials

• Christelle Haziza, PhD

  Philip Morris Products S.A.

  STUDY CHAIR

• Chris Wynne, MD

  Christchurch Clinical Studies Trust Ltd (CCST)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: August 25, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: February 1, 2016
• Last Updated: February 24, 2020
• Results First Posted: June 15, 2017

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)