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

• ClinicalTrials.gov Identifier: NCT03379740
• Recruitment Status: Completed
• First Posted: December 20, 2017
• Results First Posted: November 22, 2019
• Last Update Posted: November 22, 2019
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vaping; Nicotine Absorption	Other: E-cigarette; Other: P4M3-1.7%; Other: P4M3-1.7%LA; Other: P4M3-3%LA; Other: P4M3-4%LA	Not Applicable

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 (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• 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.
• Primary Purpose: Other
• Official Title: A Single-center, Open-label, Concentration-ranging Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of the P4M3 Variants
• Actual Study Start Date: July 11, 2017
• Actual Primary Completion Date: August 14, 2017
• Actual Study Completion Date: December 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Other: E-cigarette; Subject's own e-cigarette; Other: P4M3-1.7%; P4M3 e-liquid concentration of 1.7% nicotine without lactic acid; Other: P4M3-1.7%LA; P4M3 e-liquid concentration of 1.7% nicotine with lactic acid; Other: P4M3-3%LA; P4M3 e-liquid concentration of 3% nicotine with lactic acid; Other: P4M3-4%LA; P4M3 e-liquid concentration of 4% nicotine with lactic acid
Experimental: 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	Other: E-cigarette; Subject's own e-cigarette; Other: P4M3-1.7%; P4M3 e-liquid concentration of 1.7% nicotine without lactic acid; Other: P4M3-1.7%LA; P4M3 e-liquid concentration of 1.7% nicotine with lactic acid; Other: P4M3-3%LA; P4M3 e-liquid concentration of 3% nicotine with lactic acid; Other: P4M3-4%LA; P4M3 e-liquid concentration of 4% nicotine with lactic acid

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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 Outcome Measures :

1. Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles [ Time Frame: From Day -1 (baseline) to Day 4 ]
   To measure the total and background-corrected plasma nicotine concentration versus time profiles of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
2. Background-corrected Maximum Plasma Concentration [cCmax] [ Time Frame: From Day -1 (baseline) to Day 4 ]
   To measure the background-corrected maximum plasma concentration [cCmax] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
3. Time to the Maximum Concentration [Tmax] [ Time Frame: From Day -1 (baseline) to Day 4 ]
   To measure the time to the maximum concentration [tmax] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
4. Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] [ Time Frame: From Day -1 (baseline) to Day 4 ]
   To measure the background-corrected area under the concentration-time curve, which is above the corrected baseline from the start of product use to 4 hours [cAUC(0-4h)], of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
5. Subjective Effects of P4M3 Use [ Time Frame: From Day -1 (baseline) to Day 4 ]
   Measured with an adapted version of the modified Cigarette Evaluation Questionnaire (adapted mCEQ) within 60 minutes after the ad libitum use session. Assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
6. Area Under the Curve of Craving for an Electronic Cigarette [ Time Frame: From Day -1 (baseline) to Day 4 ]

   Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving), before and after the fixed puffing regimen and ad libitum use period. (The VAS craving was measured from 0 to 100 on a 100 mm scale.)

   The data below present the Area under the VAS craving score-time curve from the start of product use to 4 hours.

   The area under the curve for VAS craving is an integrated measurement of the VAS craving taking into account several timepoints. AUC was calculated using a trapezoidal rule between timepoints without normalization.

7. Sensory Parameters (Fixed Puffing Regimen) [ Time Frame: From Day 1 to Day 4 ]
   Measured with a Sensory Questionnaire (SQ) within 60 minutes after each fixed puffing regimen use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
8. Sensory Parameters (ad Libitum Use) [ Time Frame: From Day 1 to Day 4 ]
   Measured with a Sensory Questionnaire (SQ) within 60 minutes after each ad libitum use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
9. Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette [ Time Frame: From Day -1 (baseline) to Day 4 ]
   Total Puff Volume measured for the P4M3 variants and the subjects' own e-cigarette from the fixed puffing regimen and the 60 minutes ad libitum use.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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..

Contacts and Locations

Locations

United States, North Carolina

High Point Clinical Trials Center

High Point, North Carolina, United States, 27265

Sponsors and Collaborators

Philip Morris Products S.A.

Investigators

• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.
• Principal Investigator: Jonathan Austin, MD; High Point Clinical Trials Center

  Study Documents (Full-Text)

Documents provided by Philip Morris Products S.A.:

Study Protocol  [PDF] July 10, 2017

Statistical Analysis Plan  [PDF] July 10, 2017

More Information

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT03379740
• Other Study ID Numbers: P4M3-PK-02-US
• First Posted: December 20, 2017
• Results First Posted: November 22, 2019
• Last Update Posted: November 22, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Philip Morris Products S.A.:

Nicotine-containing product; Alternative to cigarettes