Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E-cigarette | Other | Subject's own e-cigarette |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 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. | From Day -1 (baseline) to Day 4 |
| Background-corrected Maximum Plasma Concentration [cCmax] |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Christelle Haziza, PhD | Philip Morris Products S.A. | Study Chair |
| Jonathan Austin, MD | High Point Clinical Trials Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| High Point Clinical Trials Center | High Point | North Carolina | 27265 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Product Exposure Sequence 1 | Subjects will be randomized to follow a sequence of product exposure comprised of : E-cigarette; P4M3-1.7%; P4M3-1.7%LA; P4M3-3%LA; and P4M3-4%LA E-cigarette: Subject's own e-cigarette P4M3-1.7%: P4M3 e-liquid concentration of 1.7% nicotine without lactic acid P4M3-1.7%LA: P4M3 e-liquid concentration of 1.7% nicotine with lactic acid P4M3-3%LA: P4M3 e-liquid concentration of 3% nicotine with lactic acid P4M3-4%LA: P4M3 e-liquid concentration of 4% nicotine with lactic acid |
| FG001 | Product Exposure Sequence 2 | Subjects will be randomized to follow a sequence of product exposure comprised of : E-cigarette; P4M3-1.7%LA; P4M3-1.7%; P4M3-3%LA; and P4M3-4%LA E-cigarette: Subject's own e-cigarette P4M3-1.7%: P4M3 e-liquid concentration of 1.7% nicotine without lactic acid P4M3-1.7%LA: P4M3 e-liquid concentration of 1.7% nicotine with lactic acid P4M3-3%LA: P4M3 e-liquid concentration of 3% nicotine with lactic acid P4M3-4%LA: P4M3 e-liquid concentration of 4% nicotine with lactic acid |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Product Exposure Sequence 1 | Subjects will be randomized to follow a sequence of product exposure comprised of : E-cigarette; P4M3-1.7%; P4M3-1.7%LA; P4M3-3%LA; and P4M3-4%LA E-cigarette: Subject's own e-cigarette P4M3-1.7%: P4M3 e-liquid concentration of 1.7% nicotine without lactic acid P4M3-1.7%LA: P4M3 e-liquid concentration of 1.7% nicotine with lactic acid P4M3-3%LA: P4M3 e-liquid concentration of 3% nicotine with lactic acid P4M3-4%LA: P4M3 e-liquid concentration of 4% nicotine with lactic acid |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From Day -1 (baseline) to Day 4 |
|
Adverse events were collected over the entire study duration of up to 36 days, with individual subject participation of between 15 to 36 days from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period.
The safety was assessed in the safety population, consisting of all randomized subjects who gave informed consent and had exposure to at least one of the investigational products, including product test, as part of the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | P4M3-1.7% Product Test | On Admission Day (day -2) all subjects were invited to test the P4M3 product for 10 minutes. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christelle Haziza | Philip Morris Products S.A. | +41 58 242 11 11 | ClinicalTrials.PMI@pmi.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 10, 2017 | Aug 29, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 10, 2017 | Aug 29, 2019 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000072137 | Vaping |
| ID | Term |
|---|---|
| D012907 | Smoking |
| D001519 | Behavior |
Not provided
Not provided
| ID | Term |
|---|---|
| D066300 | Electronic Nicotine Delivery Systems |
| ID | Term |
|---|---|
| D000074602 | Smoking Devices |
| D008420 | Manufactured Materials |
| D013676 | Technology, Industry, and Agriculture |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
| P4M3-1.7% | Other | P4M3 e-liquid concentration of 1.7% nicotine without lactic acid |
|
| P4M3-1.7%LA | Other | P4M3 e-liquid concentration of 1.7% nicotine with lactic acid |
|
| P4M3-3%LA | Other | P4M3 e-liquid concentration of 3% nicotine with lactic acid |
|
| P4M3-4%LA | Other | P4M3 e-liquid concentration of 4% nicotine with lactic acid |
|
To measure the background-corrected maximum plasma concentration [cCmax] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. |
| From Day -1 (baseline) to Day 4 |
| Time to the Maximum Concentration [Tmax] | To measure the time to the maximum concentration [tmax] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. | From Day -1 (baseline) to Day 4 |
| Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | 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. | From Day -1 (baseline) to Day 4 |
| Subjective Effects of P4M3 Use | 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). | From Day -1 (baseline) to Day 4 |
| Area Under the Curve of Craving for an Electronic Cigarette | 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. | From Day -1 (baseline) to Day 4 |
| Sensory Parameters (Fixed Puffing Regimen) | 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). | From Day 1 to Day 4 |
| Sensory Parameters (ad Libitum Use) | 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). | From Day 1 to Day 4 |
| Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | 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. | From Day -1 (baseline) to Day 4 |
| BG001 | Product Exposure Sequence 2 | Subjects will be randomized to follow a sequence of product exposure comprised of : E-cigarette; P4M3-1.7%LA; P4M3-1.7%; P4M3-3%LA; and P4M3-4%LA E-cigarette: Subject's own e-cigarette P4M3-1.7%: P4M3 e-liquid concentration of 1.7% nicotine without lactic acid P4M3-1.7%LA: P4M3 e-liquid concentration of 1.7% nicotine with lactic acid P4M3-3%LA: P4M3 e-liquid concentration of 3% nicotine with lactic acid P4M3-4%LA: P4M3 e-liquid concentration of 4% nicotine with lactic acid |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Weight (kg) | Mean | Full Range | kg |
|
| Height (cm) | Mean | Full Range | cm |
|
| BMI (kg/m^2) | Mean | Full Range | kg/m^2 |
|
P4M3 with e-liquid concentrations of 1.7% nicotine with lactic acid
| OG003 | P4M3-3%LA | P4M3 with e-liquid concentrations of 3% nicotine with lactic acid |
| OG004 | P4M3-4%LA | P4M3 with e-liquid concentrations of 4% nicotine with lactic acid |
|
|
| Primary | Peak Plasma Nicotine Concentration [cCpeak] | To measure background-corrected peak plasma nicotine concentration [cCpeak] from 60 minutes of ad libitum use. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From Day -1 (baseline) to Day 4 |
|
|
|
| Primary | Time to Peak Plasma Nicotine Concentration [Tpeak] | To measure the time to peak plasma nicotine concentration [tpeak] from 60 minutes of ad libitum use. | Posted | Median | Full Range | minutes | From Day -1 (baseline) to Day 4 |
|
|
|
| Primary | Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | To measure background-corrected trough plasma nicotine concentration [cCtrough] from 60 minutes of ad libitum use. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From Day -1 (baseline) to Day 4 |
|
|
|
| Primary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Background-corrected Maximum Plasma Concentration [cCmax] | To measure the background-corrected maximum plasma concentration [cCmax] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Time to the Maximum Concentration [Tmax] | To measure the time to the maximum concentration [tmax] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. | Posted | Mean | Full Range | minutes | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | 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. | Values below the Lower Limit of Quantification were set to missing. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Subjective Effects of P4M3 Use | 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). | Posted | Mean | Standard Deviation | score on a scale | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Area Under the Curve of Craving for an Electronic Cigarette | 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. | Posted | Mean | Standard Deviation | score*hr | From Day -1 (baseline) to Day 4 |
|
|
|
| Secondary | Sensory Parameters (Fixed Puffing Regimen) | 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). | Posted | Mean | Standard Deviation | score on a scale | From Day 1 to Day 4 |
|
|
|
| Secondary | Sensory Parameters (ad Libitum Use) | 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). | Posted | Mean | Standard Deviation | score on a scale | From Day 1 to Day 4 |
|
|
|
| Secondary | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | 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. | HPT raw data were reviewed for recording errors by personnel independent from the study and accepted or rejected prior to analysis. HPT data with the 'Rejected' status were excluded from the analysis. Consequently, the number of subjects analyzed differ from the overall number of subjects analyzed. | Posted | Geometric Mean | 90% Confidence Interval | mL (Total Puff Volume) | From Day -1 (baseline) to Day 4 |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 1 |
| 15 |
| EG001 | Subject's Own E-cigarette | Subject's own e-cigarette with e-liquid | 0 | 15 | 0 | 15 | 1 | 15 |
| EG002 | P4M3-1.7% | P4M3 with e-liquid concentrations of 1.7% nicotine without lactic acid | 0 | 15 | 0 | 15 | 2 | 15 |
| EG003 | P4M3-1.7%LA | P4M3 with e-liquid concentrations of 1.7% nicotine with 1.1% lactic acid | 0 | 15 | 0 | 15 | 0 | 15 |
| EG004 | P4M3-3%LA | P4M3 with e-liquid concentrations of 3% nicotine with 1.1% lactic acid | 0 | 15 | 0 | 15 | 4 | 15 |
| EG005 | P4M3-4%LA | P4M3 with e-liquid concentrations of 4% nicotine with 2% lactic acid | 0 | 15 | 0 | 15 | 2 | 15 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Diarrohea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Catheter site hypoaesthesia | General disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Catheter site inflammation | General disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA 20.0 | Non-systematic Assessment |
|
We confirm we have the contractual provisions in place which specify that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements.
The Intellectual Property rights and research results from the present study belong to the Sponsor.
| 4 mins |
|
| 7 mins |
|
| 10 mins |
|
| 15 mins |
|
| 30 mins |
|
| 60 mins |
|
| 120 mins |
|
| 240 mins |
|
|
| Ad libitum |
|
|
| Psychological Reward |
|
| Aversion |
|
| Enjoyment of Respiratory Tract Sensations |
|
| Craving Reduction |
|
| Ad Libitum |
|
| How harsh were the puffs you took? |
|
| How similar to your own brand were the puffs? |
|
| Strength of puffs on tongue? |
|
| Strength of puffs in nose? |
|
| Strength of puffs in back of mouth & throat? |
|
| Strength of puffs in windpipe? |
|
| Strength puffs in chest? |
|
| How harsh were the puffs you took? |
|
| How similar to your own brand were the puffs? |
|
| Strength of puffs on tongue? |
|
| Strength of puffs in nose? |
|
| Strength of puffs in back of mouth & throat? |
|
| Strength of puffs in windpipe? |
|
| Strength puffs in chest? |
|
|
| Ad Libitum |
|
|