Clinical trial NCT03379740: Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of P4M3 Variants
Official title: A Single-center, Open-label, Concentration-ranging Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of the P4M3 Variants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vaping
Nicotine Absorption
Keywords: Nicotine-containing product
Alternative to cigarettes
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2017-12-20
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Detailed description: The goal of the study is to evaluate the nicotine concentration profiles and derived PK parameters, subjective effects, behavioral parameters, including puffing topography parameters of P4M3 with four different variants of P4M3, in experienced e-cigarette users after a single-use experience with fixed puffing regime and after ad libitum use of P4M3.

Four variants of P4M3 will be evaluated together with subjects' own e-cigarettes to evaluate the relationship between the e-liquid composition (nicotine concentrations and presence of lactic acid) and the amount of nicotine absorbed, the speed of absorption, and the puffing topography.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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..

Primary outcomes:
measure: Plasma Nicotine Concentration Versus Time Profile
timeFrame: From Day -1 (baseline) to Day 4
measure: Peak Plasma Nicotine Concentration [cCpeak]
timeFrame: From Day -1 (baseline) to Day 4
measure: Time to Peak Plasma Nicotine Concentration [Tpeak]
timeFrame: From Day -1 (baseline) to Day 4
measure: Background-corrected Trough Plasma Nicotine Concentration [cCtrough]
timeFrame: From Day -1 (baseline) to Day 4
measure: Background-corrected Average of Plasma Nicotine Concentration [cCaverage]
timeFrame: From Day -1 (baseline) to Day 4
Secondary outcomes:
measure: Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles
timeFrame: From Day -1 (baseline) to Day 4
measure: Background-corrected Maximum Plasma Concentration [cCmax]
timeFrame: From Day -1 (baseline) to Day 4
measure: Time to the Maximum Concentration [Tmax]
timeFrame: From Day -1 (baseline) to Day 4
measure: Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)]
timeFrame: From Day -1 (baseline) to Day 4
measure: Subjective Effects of P4M3 Use
timeFrame: From Day -1 (baseline) to Day 4
measure: Area Under the Curve of Craving for an Electronic Cigarette
timeFrame: From Day -1 (baseline) to Day 4
measure: Sensory Parameters (Fixed Puffing Regimen)
timeFrame: From Day 1 to Day 4
measure: Sensory Parameters (ad Libitum Use)
timeFrame: From Day 1 to Day 4
measure: Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette
timeFrame: From Day -1 (baseline) to Day 4
Other outcomes:
Locations:
city: High Point
country: United States
facility: High Point Clinical Trials Center
state: North Carolina
Study officials:
affiliation: Philip Morris Products S.A.
name: Christelle Haziza, PhD
role: STUDY_CHAIR
affiliation: High Point Clinical Trials Center
name: Jonathan Austin, MD
role: PRINCIPAL_INVESTIGATOR
References: