Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of P4M3 Variants

NCT03379740 | Completed Results

• 1 other identifier: P4M3-PK-02-US
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, concentration-ranging study to evaluate the nicotine PK profile and PD effects in healthy adult experienced users of closed tank/cartridge e-cigarettes using four different variants of P4M3 (nicotine concentration of 1.7%, 1.7% with 1.1% lactic acid \[LA\], 3% with 1.1% LA, and 4% with 2% LA) or their own e-cigarettes.

Conditions

Vaping; Nicotine Absorption

Keywords

Nicotine-containing product; Alternative to cigarettes

Outcome Measures

Primary Outcomes (5)

• Plasma Nicotine Concentration Versus Time Profile

  To measure total and background-corrected plasma nicotine concentration versus time profiles from 60 minutes of ad libitum use.

  From Day -1 (baseline) to Day 4

• Peak Plasma Nicotine Concentration [cCpeak]

  To measure background-corrected peak plasma nicotine concentration \[cCpeak\] from 60 minutes of ad libitum use.

  From Day -1 (baseline) to Day 4

• Time to Peak Plasma Nicotine Concentration [Tpeak]

  To measure the time to peak plasma nicotine concentration \[tpeak\] from 60 minutes of ad libitum use.

  From Day -1 (baseline) to Day 4

• Background-corrected Trough Plasma Nicotine Concentration [cCtrough]

  To measure background-corrected trough plasma nicotine concentration \[cCtrough\] from 60 minutes of ad libitum use.

  From Day -1 (baseline) to Day 4

• Background-corrected Average of Plasma Nicotine Concentration [cCaverage]

  To measure background-corrected average of plasma nicotine concentration between 0 to 1 hour \[cCaverage\] from 60 minutes of ad libitum use.

  From Day -1 (baseline) to Day 4

Secondary Outcomes (9)

• Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles

  From Day -1 (baseline) to Day 4

• Background-corrected Maximum Plasma Concentration [cCmax]

  From Day -1 (baseline) to Day 4

• Time to the Maximum Concentration [Tmax]

  From Day -1 (baseline) to Day 4

• Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)]

  From Day -1 (baseline) to Day 4

• Subjective Effects of P4M3 Use

  From Day -1 (baseline) to Day 4

Study Arms (2)

Product Exposure Sequence 1

EXPERIMENTAL

Subjects will be randomized to follow a sequence of product exposure comprised of : Subject's own e-cigarette; P4M3-1.7%; P4M3-1.7%LA; P4M3-3%LA; and P4M3-4%LA

Other: E-cigarette; Other: P4M3-1.7%; Other: P4M3-1.7%LA; Other: P4M3-3%LA; Other: P4M3-4%LA

Product Exposure Sequence 2

EXPERIMENTAL

Subjects will be randomized to follow a sequence of product exposure comprised of : Subject's own e-cigarette; P4M3-1.7%LA; P4M3-1.7%; P4M3-3%LA; and P4M3-4%LA

Other: E-cigarette; Other: P4M3-1.7%; Other: P4M3-1.7%LA; Other: P4M3-3%LA; Other: P4M3-4%LA

Interventions

E-cigarette OTHER

Subject's own e-cigarette

Product Exposure Sequence 1; Product Exposure Sequence 2

P4M3-1.7% OTHER

P4M3 e-liquid concentration of 1.7% nicotine without lactic acid

Product Exposure Sequence 1; Product Exposure Sequence 2

P4M3-1.7%LA OTHER

P4M3 e-liquid concentration of 1.7% nicotine with lactic acid

Product Exposure Sequence 1; Product Exposure Sequence 2

P4M3-3%LA OTHER

P4M3 e-liquid concentration of 3% nicotine with lactic acid

Product Exposure Sequence 1; Product Exposure Sequence 2

P4M3-4%LA OTHER

P4M3 e-liquid concentration of 4% nicotine with lactic acid

Product Exposure Sequence 1; Product Exposure Sequence 2

Eligibility Criteria

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

You may qualify if:

• Subject has signed the informed consent form (ICF) and is able to understand the information provided in the ICF.
• Subject is 21 to 65 years of age, inclusive, at the Screening Visit.
• Subject is a former daily cigarette smoker who smoked at least 100 cigarettes or more in his/her life and ceased smoking at least 3 months prior to the Screening Visit.
• Subject has been using a commercially available, nicotine-containing closed tank/cartridge e-cigarette daily for at least 3 months prior to the Screening Visit.
• Subject has a urine cotinine test ≥200 ng/mL at the Screening Visit and Admission.

You may not qualify if:

• Subject has a clinically relevant disease which requires medication which as per the judgment of the Investigator would jeopardize the safety of the subject.
• Subject has abnormal renal function test result or subject with a creatinine clearance \<60 mL/minute at the Screening Visit, confirmed on repeat testing.
• Subject has elevated liver function test results at the Screening Visit.
• Subject has bilirubin \>1.5X ULN at the Screening Visit.
• Subject has FEV1/FVC \<0.7 and FEV1 \<80% predicted value at post-bronchodilator spirometry at the Screening Visit.
• Subject has asthma condition at the Screening Visit.
• Subject has received medication within 14 days or within 5 half-lives of the drug (whichever is longer) prior to Admission, which has an impact on cytochrome P450 (CYP) 2A6 activity.
• Subject has a carbon monoxide (CO) breath test ≥ 10 ppm at the Screening Visit or Admission.
• Subject has a body mass index (BMI) \<18.5 kg/m2 or BMI ≥35 kg/m2 at the Screening Visit.
• Subject has a positive serology test for human immunodeficiency virus (HIV) 1/2, hepatitis B, or hepatitis C at the Screening Visit.
• Subject has clinically significant ECG findings at the Screening Visit.
• Subject has participated in a clinical study within 3 months prior to the Screening Visit.
• Subject smokes cigarettes or uses other tobacco products.
• Female subject of childbearing potential who is pregnant or breastfeeding.
• Female subject of childbearing potential who does not agree to use an acceptable method of effective contraception..

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (1)

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

MeSH Terms

Conditions

Vaping

Interventions

Electronic Nicotine Delivery Systems

Condition Hierarchy (Ancestors)

Smoking; Behavior

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Christelle Haziza
• Organization: Philip Morris Products S.A.

ClinicalTrials.PMI@pmi.com

+41 58 242 11 11

Study Officials

• Christelle Haziza, PhD

  Philip Morris Products S.A.

  STUDY CHAIR

• Jonathan Austin, MD

  High Point Clinical Trials Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study; however the site (except the pharmacy staff preparing the IPs for administration) will be masked to the randomization sequences until they are assigned. Subjects will not be informed of the complete sequence to which they have been assigned to receive the P4M3 products.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: December 20, 2017
• Study Start: July 11, 2017
• Primary Completion: August 14, 2017
• Study Completion: December 1, 2017
• Last Updated: November 22, 2019
• Results First Posted: November 22, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)