A Single-center, Open-label, Concentration-ranging Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of the P4M3 Variants
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Plasma Nicotine Concentration Versus Time Profile
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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..
结局指标
主要结局
Plasma Nicotine Concentration Versus Time Profile
时间窗: 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]
时间窗: 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]
时间窗: 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]
时间窗: 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]
时间窗: 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.
次要结局
- 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)
- 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)