A Single-center, Open-label, Concentration-ranging Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of the P4M3 Variants
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Philip Morris Products S.A.
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Plasma Nicotine Concentration Versus Time Profile
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Masking Description
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.
Eligibility Criteria
- Ages
- 21 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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..
Arms & Interventions
Product Exposure Sequence 2
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
Intervention: P4M3-1.7% (Other)
Product Exposure Sequence 2
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
Intervention: P4M3-1.7%LA (Other)
Product Exposure Sequence 2
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
Intervention: P4M3-3%LA (Other)
Product Exposure Sequence 2
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
Intervention: P4M3-4%LA (Other)
Product Exposure Sequence 1
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
Intervention: P4M3-1.7% (Other)
Product Exposure Sequence 1
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
Intervention: E-cigarette (Other)
Product Exposure Sequence 1
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
Intervention: P4M3-1.7%LA (Other)
Product Exposure Sequence 1
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
Intervention: P4M3-3%LA (Other)
Product Exposure Sequence 1
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
Intervention: P4M3-4%LA (Other)
Product Exposure Sequence 2
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
Intervention: E-cigarette (Other)
Outcomes
Primary Outcomes
Plasma Nicotine Concentration Versus Time Profile
Time Frame: From Day -1 (baseline) to Day 4
To measure total and background-corrected plasma nicotine concentration versus time profiles from 60 minutes of ad libitum use.
Peak Plasma Nicotine Concentration [cCpeak]
Time Frame: From Day -1 (baseline) to Day 4
To measure background-corrected peak plasma nicotine concentration \[cCpeak\] from 60 minutes of ad libitum use.
Time to Peak Plasma Nicotine Concentration [Tpeak]
Time Frame: From Day -1 (baseline) to Day 4
To measure the time to peak plasma nicotine concentration \[tpeak\] from 60 minutes of ad libitum use.
Background-corrected Trough Plasma Nicotine Concentration [cCtrough]
Time Frame: From Day -1 (baseline) to Day 4
To measure background-corrected trough plasma nicotine concentration \[cCtrough\] from 60 minutes of ad libitum use.
Background-corrected Average of Plasma Nicotine Concentration [cCaverage]
Time Frame: From Day -1 (baseline) to Day 4
To measure background-corrected average of plasma nicotine concentration between 0 to 1 hour \[cCaverage\] from 60 minutes of ad libitum use.
Secondary Outcomes
- Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)](From Day -1 (baseline) to Day 4)
- 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)
- Subjective Effects of P4M3 Use(From Day -1 (baseline) to Day 4)
- Area Under the Curve of Craving for an Electronic Cigarette(From Day -1 (baseline) to Day 4)
- Sensory Parameters (Fixed Puffing Regimen)(From Day 1 to Day 4)
- Sensory Parameters (ad Libitum Use)(From Day 1 to Day 4)
- Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette(From Day -1 (baseline) to Day 4)