A Study to Evaluate Nicotine Uptake and Biomarkers in Adult Smokers Using mybluTM Electronic Cigarettes

An Open-Label, Randomized, Crossover Study to Assess Nicotine Uptake, Tobacco-Related Biomarkers of Exposure, Biomarkers of Potential Harm, and Puff Topography With Use of mybluTM Electronic Cigarettes in Adult Smokers

This study evaluates the overall performance of the currently-marketed MybluTM e-cigarette device and pods, as assessed by nicotine uptake, exposure to smoke constituents, safety and consumer satisfaction, over 8 days. The study is designed as an open-label, randomized study in adult smokers.

Subjects are invited to participate to a second part of the study, for 5 additional days, to compare the use of MybluTM to the use of subject's usual brand combustible cigarettes.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Other: Myblu flavor A_2.4; Other: Myblu flavor B_2.4; Other: Myblu flavor C_2.4; Other: Myblu flavor D_2.4; Other: Myblu flavor E_1.2; Other: Myblu flavor F_1.2; Other: Myblu flavor G_2.4; Other: Myblu flavor H_2.4

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• smoking an average of at least 10 manufactured combustible cigarettes per day for at least 12 months prior to Screening
• tested positive for urine cotinine (≥ 200 ng/mL) at Screening
• exhaled carbon monoxide > 10 ppm (parts per million) at Screening

Exclusion Criteria:

• relevant illness history
• relevant medication use
• body mass index (BMI) > 40 kg/m2 or < 18 kg/m2 at Screening
• allergy to propylene glycol or glycerin
• use of nicotine-containing products other than manufactured combustible cigarettes within 14 days prior to Check-in
• use of any prescription smoking cessation treatments within 3 months prior to Check-in
• smokers who draw smoke from the cigarette into the mouth and throat but do not inhale
• planning to quit smoking during the study
• female subjects who are pregnant, lactating, or intend to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Product use sequence ABDC; Subjects use MybluTM e-cigarette product variant A (2.4% nicotine) ad libitum for 2 days, then switch to use variant B (2.4% nicotine) for 2 days, then D (2.4% nicotine) for 2 days and then C (2.4% nicotine) for 2 days. A washout period of 12 hours product abstinence is observed between product variants. For each product variant, in the morning of the second product use day, a controlled product use session is performed (10 puffs taken at 30-second intervals, with puffs 3 seconds in duration).	Other: Myblu flavor A_2.4; Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine; Other: Myblu flavor B_2.4; Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine; Other: Myblu flavor C_2.4; Use of Myblu e-cigarette with flavor C at 2.4% nicotine; Other: Myblu flavor D_2.4; Use of Myblu e-cigarette with flavor D at 2.4% nicotine
Experimental: Product use sequence BCAD; Same as previous arm, but in a different randomization order.	Other: Myblu flavor A_2.4; Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine; Other: Myblu flavor B_2.4; Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine; Other: Myblu flavor C_2.4; Use of Myblu e-cigarette with flavor C at 2.4% nicotine; Other: Myblu flavor D_2.4; Use of Myblu e-cigarette with flavor D at 2.4% nicotine
Experimental: Product use sequence CDBA; Same as previous arm, but in a different randomization order.	Other: Myblu flavor A_2.4; Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine; Other: Myblu flavor C_2.4; Use of Myblu e-cigarette with flavor C at 2.4% nicotine; Other: Myblu flavor D_2.4; Use of Myblu e-cigarette with flavor D at 2.4% nicotine
Experimental: Product use sequence DACB; Same as previous arm, but in a different randomization order.	Other: Myblu flavor A_2.4; Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine; Other: Myblu flavor B_2.4; Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine; Other: Myblu flavor C_2.4; Use of Myblu e-cigarette with flavor C at 2.4% nicotine; Other: Myblu flavor D_2.4; Use of Myblu e-cigarette with flavor D at 2.4% nicotine
Experimental: Product use sequence EFHG; Subjects use MybluTM e-cigarette product variant E (1.2% nicotine) ad libitum for 2 days, then switch to use variant F (1.2% nicotine) for 2 days, then H (2.4% nicotine) for 2 days and then G (2.4% nicotine) for 2 days. A washout period of 12 hours product abstinence is observed between product variants. For each product variant, in the morning of the second product use day, a controlled product use session is performed (10 puffs taken at 30-second intervals, with puffs 3 seconds in duration).	Other: Myblu flavor E_1.2; Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine; Other: Myblu flavor F_1.2; Fse of Myblu e-cigarette with flavor F at 1.2% nicotine; Other: Myblu flavor G_2.4; Use of Myblu e-cigarette with flavor G at 2.4% nicotine; Other: Myblu flavor H_2.4; Use of Myblu e-cigarette with flavor H at 2.4% nicotine
Experimental: Product use sequence FGEH; Same as previous arm, but in a different randomization order.	Other: Myblu flavor E_1.2; Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine; Other: Myblu flavor F_1.2; Fse of Myblu e-cigarette with flavor F at 1.2% nicotine; Other: Myblu flavor G_2.4; Use of Myblu e-cigarette with flavor G at 2.4% nicotine; Other: Myblu flavor H_2.4; Use of Myblu e-cigarette with flavor H at 2.4% nicotine
Experimental: Product use sequence GHFE; Same as previous arm, but in a different randomization order.	Other: Myblu flavor E_1.2; Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine; Other: Myblu flavor F_1.2; Fse of Myblu e-cigarette with flavor F at 1.2% nicotine; Other: Myblu flavor G_2.4; Use of Myblu e-cigarette with flavor G at 2.4% nicotine; Other: Myblu flavor H_2.4; Use of Myblu e-cigarette with flavor H at 2.4% nicotine
Experimental: Product use sequence HEGF; Same as previous arm, but in a different randomization order.	Other: Myblu flavor E_1.2; Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine; Other: Myblu flavor F_1.2; Fse of Myblu e-cigarette with flavor F at 1.2% nicotine; Other: Myblu flavor G_2.4; Use of Myblu e-cigarette with flavor G at 2.4% nicotine; Other: Myblu flavor H_2.4; Use of Myblu e-cigarette with flavor H at 2.4% nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Nicotine Concentration in Blood	Maximum nicotine concentration in blood (Cmax)	180 minutes following the start of the controlled product use session on Day 2 (12 measurements over the period)
Concentration of Carboxyhemoglobin in Blood	Change from baseline in the concentration of carboxyhemoglobin (COHb) in whole blood.	Baseline and 8 days
Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours	Change from baseline in the amount of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a biomarker of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), excreted in urine during 24 hours (creatinine adjusted).	Baseline and 8 days
Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours	Change from baseline in the amount of 3-hydroxypropylmercapturic acid (3-HPMA), a biomarker of exposure to acrolein, excreted in urine during 24 hours (creatinine adjusted).	Baseline and 8 days
Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours	Change from baseline in the amount of S-phenyl mercapturic acid (S-PMA), a biomarker of exposure to benzene, excreted in urine during 24 hours (creatinine adjusted).	Baseline and 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of White Blood Cells	The change from baseline in the level of white blood cells, a biomarker of potential harm.	Baseline and 8 days
Spirometry: Forced Expiratory Volume in 1 Second	The percent-predicted forced expiratory volume in 1 second (FEV1) measurement conducted in accordance with the 2005 American Thoracic Society / European Respiratory Society Joint Task Force on the standardization of spirometry, with subject in a sitting position following at least 15 minutes of rest and at least 1 hour from the last product use.	Baseline and 8 days
Spirometry: Forced Vital Capacity	The percent-predicted forced vital capacity (FVC) measurement conducted in accordance with the 2005 American Thoracic Society / European Respiratory Society Joint Task Force on the standardization of spirometry, with subject in a sitting position following at least 15 minutes of rest and at least 1 hour from the last product use.	Baseline and 8 days
Subjective Measure: Urge to Smoke	Urge to smoke score: Subjects answer the following question "How strong is your urge to smoke right now?" using a visual analogue scale. The scale ranges from "Not at all", given a score of 0, to "Extremely", given a score of 100, after ad libitum use of the product.	8 days

Collaborators and Investigators

• Sponsor: Fontem US LLC
• Collaborators: Fontem Ventures BV

Publications and helpful links

General Publications

• Morris P, McDermott S, Chapman F, Verron T, Cahours X, Stevenson M, Thompson J, Chaudhary N, O'Connell G. Reductions in biomarkers of exposure to selected harmful and potentially harmful constituents following exclusive and partial switching from combustible cigarettes to myblu electronic nicotine delivery systems (ENDS). Intern Emerg Med. 2022 Mar;17(2):397-410. doi: 10.1007/s11739-021-02813-w. Epub 2021 Aug 26.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: CA22736

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No