Changes in Biomarker of Exposure in Adults Who Smoke Cigarettes Switching From Cigarettes to Heated Tobacco Products

NCT06179290 | Completed Results

• 1 other identifier: ALCS-REG-23-07-HT
• Study Type: interventional
• Target: 921
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of the study is to evaluate changes in biomarkers of exposure (BoE) to harmful and potentially harmful constituents (HPHCs) in adult smokers who completely switch to Ploom heated tobacco products (HTPs) compared to those who continue to smoke usual brand combustible cigarettes (UBCC).

Conditions

Tobacco Use

Keywords

Tobacco; Smoking; Heated tobacco

Outcome Measures

Primary Outcomes (14)

• Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)

  Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• Total N-nitrosonornicotine (NNN)

  Total N-nitrosonornicotine (NNN) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• 2-hydroxybutenylmercapturic Acid (2-MHBMA)

  2-hydroxybutenylmercapturic acid (2-MHBMA) in urine adjusted for urine creatinine (ng/mg creatinine)

  Baseline through Day 5

• 3-hydroxypropylmercapturic Acid (3-HPMA)

  3-hydroxypropylmercapturic acid (3-HPMA) in urine adjusted for urine creatinine (ng/mg creatinine)

  Baseline through Day 5

• S-phenyl Mercapturic Acid (SPMA)

  S-phenyl mercapturic acid (SPMA) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• 2-Hydroxyethyl Mercapturic Acid (HEMA)

  2-Hydroxyethyl mercapturic acid (HEMA) in urine adjusted for urine creatinine (ng/mg creatinine)

  Baseline through Day 5

• 1-aminonaphthalene (1-AN)

  1-aminonaphthalene (1-AN) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• 2-aminonaphthalene (2-AN)

  2-aminonaphthalene (2-AN) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• 2-cyanoethyl-mercapturic Acid (CEMA)

  2-cyanoethyl-mercapturic acid (CEMA) in urine adjusted for urine creatinine (ng/mg creatinine)

  Baseline to Day 5

• 3-hydroxybenzo[a]Pyrene (3-OH-B[a]P)

  3-hydroxybenzo\[a\]pyrene (3-OH-B\[a\]P) in urine adjusted for urine creatinine (fg/mg creatinine)

  Baseline through Day 5

• 3-hydroxy-1-methylpropylmercapturic Acid (HMPMA)

  3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in urine adjusted for urine creatinine (ng/mg creatinine)

  Baseline through Day 5

• 4-Aminobiphenyl (4-ABP)

  4-Aminobiphenyl (4-ABP) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• S-benzyl Mercapturic Acid (SBMA)

  S-benzyl mercapturic acid (SBMA) in urine adjusted for urine creatinine (pg/mg creatinine)

  Baseline through Day 5

• Carboxyhemoglobin (COHb)

  COHb, or carboxyhemoglobin, is the percent of hemoglobin that is bound to carbon monoxide instead of oxygen

  Baseline to Day 5

Study Arms (6)

Study Product A: Ploom HTP Menthol HTS; MX3 (681)

EXPERIMENTAL

Subjects in A arm (Group 1 Menthol) will be required to smoke Ploom HTP Menthol HTS; MX3 (681) study product at least 5 times per day ad libitum from 07:00 through 23:00. There will be 60 subjects assigned to this arm with a randomization ratio of 2.

Other: Ploom HTP Menthol HTS; MX3 (681)

Study Product B: Continue Smoking (menthol)

NO INTERVENTION

Subjects in B arm (Group 1 Menthol) will continue to smoke their menthol UBCC ad libitum from 07:00 through 23:00. There will be 60 subjects assigned to this arm with a randomization ratio of 2.

Study Product C: Smoking Abstinence (menthol)

ACTIVE COMPARATOR

Subjects in C arm (Group 1 Menthol) will remain abstinent from cigarette smoking for the duration of the study during both the confinement and ambulatory phases. There will be 30 subjects assigned to this arm with a randomization ratio of 1.

Other: Smoking Abstinence (menthol)

Study Product D: Ploom HTP Tobacco HTS; R8 (120)

EXPERIMENTAL

Subjects in D arm (Group 2 Non-menthol) will be required to smoke Ploom HTP Tobacco HTS; R8 (120) study product at least 5 times per day ad libitum from 07:00 through 23:00. There will be 60 subjects assigned to this arm with a randomization ratio of 2.

Other: Ploom HTP Tobacco HTS; R8 (120)

Study Product E: Continue Smoking (non-menthol)

NO INTERVENTION

Subjects in E arm (Group 2 Non-menthol) will continue to smoke their non-menthol UBCC ad libitum from 07:00 through 23:00. There will be 60 subjects assigned to this arm with a randomization ratio of 2.

Study Product F: Smoking Abstinence (non-menthol)

ACTIVE COMPARATOR

Subjects in F arm (Group 2 Non-menthol) will remain abstinent from cigarette smoking for the duration of the study during both the confinement and ambulatory phases. There will be 30 subjects assigned to this arm with a randomization ratio of 1.

Other: Smoking Abstinence (non-menthol)

Interventions

Ploom HTP Menthol HTS; MX3 (681) OTHER

Menthol heated tobacco product

Study Product A: Ploom HTP Menthol HTS; MX3 (681)

Ploom HTP Tobacco HTS; R8 (120) OTHER

Non-menthol heated tobacco product

Study Product D: Ploom HTP Tobacco HTS; R8 (120)

Smoking Abstinence (menthol) OTHER

No smoking or other tobacco product use for duration of the study, menthol group comparator

Study Product C: Smoking Abstinence (menthol)

Smoking Abstinence (non-menthol) OTHER

No smoking or other tobacco product use for duration of the study, non-menthol group comparator

Study Product F: Smoking Abstinence (non-menthol)

Eligibility Criteria

• Age: 22 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary consent to participate in this study documented on the signed ICF.
• Score 5 or higher (moderate dependence or higher) on the FTCD.
• Healthy adult males and females ≥ 22 and ≤ 65 years of age, inclusive, at Screening.
• Smoking history (self-reported at screening) of an average of at least 10 but no more than 30 factory-manufactured combustible cigarettes (either menthol or non-menthol) daily for at least 12 months prior to screening. Brief periods (ie, up to 7 consecutive days) of non-smoking during the 3 months prior to screening (eg, due to illness or participation in a study where smoking was prohibited) will be permitted.
• Screening and first check-in blood pressure ≤ 150/90 mmHg measured after being seated for at least 10 minutes. Two rechecks may be performed at the Principal Investigator's discretion.
• Positive urine cotinine (≥ 500 ng/mL) at screening.
• Exhaled carbon monoxide (eCO) ≥ 10 ppm at screening.
• Post-bronchodilator forced expired volume in 1 second (FEV1) : forced vital capacity (FVC) ratio \> 0.7 and FEV1 \> 80% of predicted at screening.
• Negative pregnancy test at Screening and first check-in (Day -2) for all female subjects.
• Female subjects who are heterosexually active and of childbearing potential (eg, neither surgically sterile at least 6 months prior to first check-in nor postmenopausal with amenorrhea for at least 12 months prior to first check-in with follicle-stimulating hormone \[FSH\] levels consistent with postmenopausal status) must have been using one of the following forms of contraception for the time period indicated and agree to continue using it through completion of the study:
• hormonal (eg, oral, vaginal ring, transdermal patch, implant, injection) consistently for at least 3 months prior to first check-in, when used in combination with male condoms with spermicide (use of NuvaRing® is at the Principal Investigator's discretion)
• double barrier (eg, condom with spermicide or diaphragm with spermicide) consistently for at least 2 weeks prior to first check-in
• intrauterine device or system (utilize Principal Investigator discretion regarding use of hormonal or nonhormonal devices) for at least 3 months prior to first check-in
• exclusive partner who is clinically sterile (ie, documented infertility or surgical sterilization; see below for additional information on sterility) or has been vasectomized for at least 6 months (inclusive) prior to first check-in Note: Sexual abstinence, defined as refraining from intercourse, is allowed when this is in line with the preferred and usual lifestyle of the subject. Female subjects of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.
• Female subjects who are of nonchildbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to first check-in:

You may not qualify if:

• Use of any type of tobacco- or nicotine-containing products other than manufactured cigarettes (eg, e-vapor products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) in the 7 days prior to first check-in.
• Self-reported puffers (ie, adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale).
• Planning to quit smoking in the next three months (at screening).
• History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, existing respiratory diseases, immunologic, psychiatric, lymphatic, or cardiovascular disease, or any other condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• Clinically significant abnormal findings on the vital signs, physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Principal Investigator.
• Positive test for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at screening.
• History or presence of any type of malignant tumors.
• Current evidence or any history of congestive heart failure.
• Diabetes mellitus (fasting glucose ≥126 mg/L \[7 mmol/L\]) that is not controlled by diet/exercise alone, in the opinion of the Principal Investigator.
• An acute illness (eg, upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to first check-in.
• Any planned surgery from the time of screening through EOS.
• History of drug or alcohol abuse within 24 months prior to first check-in.
• Fever (ie, body temperature \>100.5°F) at screening or first check-in. One re-check may be performed at the Principal Investigator's discretion.
• Body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at screening.
• Systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 90 mmHg at screening or first check-in, measured after being seated for at least 10 minutes. Two re-checks may be performed at the Principal Investigator's discretion.

Sponsors & Collaborators

• Altria Client Services LLC: lead
• Celerion: collaborator

Study Sites (8)

Pillar Clinical Research

Bentonville, Arkansas, 72712, United States

Location

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

Location

Dr. Vince Clinical Research, LLC

Overland Park, Kansas, 66212, United States

Location

Alliance for Multispecialty Research, LLC

Lexington, Kentucky, 40509, United States

Location

QPS Bio-Kinetic

Springfield, Missouri, 65802, United States

Location

Celerion Lincoln

Lincoln, Nebraska, 68502, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37920, United States

Location

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Conditions

Tobacco Use; Smoking

Interventions

Menthol

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Cyclohexane Monoterpenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Monoterpenes; Terpenes; Lipids

Results Point of Contact

• Title: Jeffery Edmiston
• Organization: Altria

Jeffery.S.Edmiston@altria.com

8043352366

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-site, open-label, two-group (menthol and non-menthol), six-arm (HTP, Continue Smoking, and Smoking Abstinence arms within each group) randomized, clinical study to evaluate changes in BoEs in adult smokers who remain smoking, switch to the Ploom HTP, or abstain from smoking, for 60 days (5 days in clinic followed by 55-day ambulatory phase). This study follows the recommendations of the FDA's final Premarket Tobacco Product Application guidance (FDA, 2023).

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: December 21, 2023
• Study Start: October 2, 2023
• Primary Completion: May 15, 2024
• Study Completion: March 24, 2025
• Last Updated: May 27, 2026
• Results First Posted: May 27, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)