A Study to Evaluate Changes in Smokers Using Oral Tobacco-derived Nicotine Products.

A Randomized, Controlled, Study to Evaluate Changes in Exposure to Harmful and Potentially Harmful Constituents in Adult Smokers Who Partially or Completely Switch to Oral Tobacco-derived Nicotine Products in a Clinical Setting.

The purpose of this study is to evaluate changes in exposure to selected harmful and potentially harmful constituents (HPHC) by measuring biomarkers in adult smokers who partially or completely switch from smoking cigarettes to oral tobacco-derived nicotine (OTDN) products compared to those who continue exclusive smoking cigarettes or stop using all tobacco products.

Study Overview

• Status: Completed
• Conditions: Tobacco Use
• Intervention / Treatment: Other: OTDN product 1; Other: OTDN product 2; Other: Tobacco Cessation

Detailed Description

This is an open label, randomized, 6 parallel-group clinical study evaluating changes in exposure to selected HPHCs, subjective effects, and product use behavior in adult smokers relative to continued smoking who are randomly assigned to continue smoking, partially or completely switch to oral tobacco-derived nicotine products, or stop using any tobacco products for 7 days.

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Springfield, Missouri, United States, 65802
      • QPS Bio-Kinetic Clinical Applications, LLC
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Inflamax - Hill Top Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary consent to participate in this study documented on the signed informed consent form (ICF).
2. Healthy adult males and females 21 to 65 years of age, inclusive, at Screening
3. Smoking history of an average of at least 10 but no more than 30 factory manufactured combustible cigarettes daily for at least 1 year prior to Screening. Brief periods (i.e., up to 7 consecutive days) of non-smoking during the 3 months prior to Screening (e.g., due to illness or participation in a study where smoking was prohibited) will be permitted.
4. Positive urine cotinine (≥ 500 ng/mL) at Screening.
5. Willing to comply with the requirements of the study.
6. Willing to use all test products after product trial at Check in.
7. Willing and able to abstain from cigarettes from Day 1 through the End of the study.

Exclusion Criteria:

1. Use of any type of tobacco or nicotine containing products other than manufactured cigarettes (e.g., 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 Check in
2. Self-reported puffers (i.e., adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale).
3. Planning to quit smoking in the next 30 days (from Screening visit).
4. 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 Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
5. Clinically significant abnormal findings on the vital signs, physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: GROUP 1: Continue Smoking; Subjects will be asked to continue smoking their own brand (OB) cigarettes ad libitum for 7 days.
Experimental: GROUP 2: OTDN product 1; Subjects will reduce their normal daily cigarette consumption by at least 50% of their baseline cigarettes per day (CPD) and use at least 3 oral tobacco-derived nicotine (OTDN) product units per day for 7 days.	Other: OTDN product 1; Oral tobacco-derived nicotine product
Experimental: GROUP 3: OTDN product 2; Subjects will reduce their normal daily cigarette consumption by at least 50% of their baseline CPD and use at least 3 oral tobacco-derived nicotine (OTDN) product units per day for 7 days.	Other: OTDN product 2; Oral tobacco-derived nicotine product
Experimental: GROUP 4: OTDN product 1; Subjects will completely switch to exclusive use of an oral tobacco-derived nicotine (OTDN) product, using at least 3 OTDN product units per day for 7 days.	Other: OTDN product 1; Oral tobacco-derived nicotine product
Experimental: GROUP 5: OTDN product 2; Subjects will completely switch to exclusive use of an oral tobacco-derived nicotine (OTDN) product, using at least 3 OTDN product units per day for 7 days.	Other: OTDN product 2; Oral tobacco-derived nicotine product
Experimental: GROUP 6: Tobacco Cessation; Subjects will completely stop all tobacco product usage for 7 days.	Other: Tobacco Cessation; Tobacco Cessation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Urine Total NNAL Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)	Summary of urine total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) amount excreted (ng/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the lower limit of quantitation (LLOQ) (2.00 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of Urine Total NNAL Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of urine total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (2.00 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of NNN Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)	Summary of N-nitrosonornicotine (NNN) amount excreted (ng/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.500 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of NNN Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of N-nitrosonornicotine (NNN) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.500 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of Nicotine Equivalents Amount Excreted and Absolute Change From Baseline (mg/24 Hour) by Study Group and Study Day (mITT Population)	Summary of nicotine equivalents amount excreted (mg/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) for each metabolite were set to one-half of the LLOQ for the calculation of nicotine equivalents. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Nicotine equivalents (mg/g creatinine) = nicotine equivalents (μg/mL) x 100 / creatinine (mg/dL) Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of Nicotine Equivalents Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of nicotine equivalents amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) for each metabolite were set to one-half of the LLOQ for the calculation of nicotine equivalents. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Nicotine equivalents (mg/g creatinine) = nicotine equivalents (μg/mL) x 100 / creatinine (mg/dL) % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 2-AN Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-aminonaphthalene (2-AN) amount excreted (ng/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (1.7 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 2-AN Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-aminonaphthalene (2-AN) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (1.7 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 4-ABP Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 4-aminobiphenyl (4-ABP) amount excreted (ng/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (1.5 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 4-ABP Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 4-aminobiphenyl (4-ABP) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (1.5 pg/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of HEMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-hydroxyethyl mercapturic acid (HEMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.2 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of HEMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-hydroxyethyl mercapturic acid (HEMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.2 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of CEMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-cyanoethylmercapturic acid (CEMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.25 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of CEMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-cyanoethylmercapturic acid (CEMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.25 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of S-PMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of S-phenyl mercapturic acid (S-PMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.02 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of S-PMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of S-phenyl mercapturic acid (S-PMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.02 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 3-HMPMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 3-hydroxy-1-methylpropylmercapturic acid (3-HMPMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (5 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 3-HMPMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 3-hydroxy-1-methylpropylmercapturic acid (3-HMPMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (5 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 3-HPMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 3-hydroxypropylmercapturic acid (3-HPMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (25 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 3-HPMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 3-hydroxypropylmercapturic acid (3-HPMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (25 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 2-HPMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-hydroxypropyl-mercapturic acid (2-HPMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (2.5 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 2-HPMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-hydroxypropyl-mercapturic acid (2-HPMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (2.5 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of AAMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (10 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of AAMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original Values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (10 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of GAMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (1 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of GAMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (1 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 2-MHBMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-hydroxybutenyl-mercapturic acid (2-MHBMA) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.129 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 2-MHBMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-hydroxybutenyl-mercapturic acid (2-MHBMA) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.129 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 2-OHFLe Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-OH-Fluorene (2-OHFLe) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.1 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 2-OHFLe Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-OH-Fluorene (2-OHFLe) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.1 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 2-Naphthol Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 2-Naphthol amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.10 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 2-Naphthol Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 2-Naphthol amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.10 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 1-OHPhe Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 1-OH-Phenanthrene (1-OHPhe) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.005 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 1-OHPhe Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 1-OH-Phenanthrene (1-OHPhe) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.005 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of 1-OHP Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)	Summary of 1-hydroxypyrene (1-OHP) amount excreted (ug/24 hour) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.01 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of 1-OHP Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of 1-hydroxypyrene (1-OHP) amount excreted percent change from Baseline (%) is presented. Subjects with valid sample results are included. Original values reported as below the limit of quantitation (BLQ) were set to one-half of the LLOQ (0.01 ng/mL) for summarization and statistical analysis. Baseline = Day -1. 24-hour urine collections occurred on Days -1, 5, and 7 beginning after the first morning void and any void prior to 07:00, and finished the following morning with the last void collected at approximately 07:00 (including first morning void). % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of Urine Mutagenicity and Absolute Change From Baseline (Revertants/24 Hours) by Study Group and Study Day (mITT Population)	Summary of urine mutagenicity (revertants/24 hours) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Baseline = Day -1. 250 mL urine sample will be concentrated to 1 mL and used for urine mutagenicity testing. The measurement results will be reported as revertants/μL. The urine mutagenicity count in the 24 hour urine will be calculated as: Urine mutagenicity (revertants/24 hour) = Urine mutagenicity (revertants/250 mL) x urine volume/ urine sample volume in mL Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of Urine Mutagenicity Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of urine mutagenicity percent change from Baseline (%) by study group and study day is presented. Baseline = Day -1. 250 mL urine sample will be concentrated to 1 mL and used for urine mutagenicity testing. The measurement results will be reported as revertants/μL. The urine mutagenicity count in the 24 hour urine will be calculated as: Urine mutagenicity (revertants/24 hour) = Urine mutagenicity (revertants/250 mL) x urine volume/ urine sample volume in mL % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Summary of Whole Blood COHb and Absolute Change From Baseline (% Saturation) by Study Group and Study Day (mITT Population)	Summary of whole blood carboxyhemoglobin [COHb] (% saturation) by study group on Days -1, 5 and 7, and absolute change from Baseline on Days 5 and 7 are presented. Subjects with valid sample results are included. Baseline = Day -1. The blood sample for COHb was collected approximately 21:30 on Days -1, 5, and 7 after subjects abstained from product use, as appropriate, for at least 15 minutes prior to blood draw for COHb. Absolute change from baseline was calculated as: Post Randomization Value - Baseline Value	Baseline (Day -1), Day 5 and Day 7
Summary of Whole Blood COHb Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)	Summary of whole blood carboxyhemoglobin (COHb) percent change from Baseline (%) is presented. Subjects with valid sample results are included. Baseline = Day -1. The blood sample for COHb was collected approximately 21:30 on Days -1, 5, and 7 after subjects abstained from product use, as appropriate, for at least 15 minutes prior to blood draw for COHb. % change from Baseline = (Post Randomization Value - Baseline Value) / Baseline Value x 100 %	Day 5 and Day 7
Cigarette Consumption by Study Group and Study Day (mITT Population)	Summary of cigarette consumption, as number of cigarettes smoked per day (CPD), by study group and study day is presented. Baseline = Average of Days -2 and -1.	Day -1 and Day -2 (Baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
Summary of VERVE® Product Usage by Study Group and Study Day (mITT Population)	Summary of VERVE® Product Used Per Day by Study Group and Study Day is presented. Only study groups that received the test product (VERVE® Discs or VERVE® Chews) are shown. Results are stratified by product flavor (Green Mint, Blue Mint and overall).	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
Summary of VERVE® Product Use Duration by Study Group and Study Day (mITT Population)	Summary of average VERVE® product use duration (minutes) by Study Group and Study Day is presented. Only study groups that received the test product (VERVE® Discs or VERVE® Chews) are shown. Results are stratified by product flavor (Green Mint, Blue Mint and overall).	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
Summary of Total Duration (Min) of VERVE® Product Per Day by Study Group and Study Day (mITT Population)	Summary of total duration (minutes) of VERVE® product per day by Study Group and Study Day. Only study groups that received the test product (VERVE® Discs or VERVE® Chews) are shown. Results are stratified by product flavor (Green Mint, Blue Mint and overall).	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
Summary of Response for Willingness to Use Cigarettes Again Bipolar VAS Scores for Cigarettes by Category, Study Group and Study Product (mITT Population)	Summary of subject responses to "Use the Product (Cigarette) Again" Bipolar Visual Analogue Scale (VAS) Scores for cigarettes is presented. The Use the Product Again Bipolar VAS is a 100 mm scale ranging from 0 mm ("Definitely Would Not") to 100 mm ("Definitely Would"). The bipolar score is calculated by subtracting 50 from the original VAS score, then categorizing into three categories: -50 to <0, 0, and >0 to 50. Higher scores are associated with greater willingness to use the cigarettes again. Mean and standard deviation of the bipolar VAS score per category is shown. The "Use the Product Again" VAS Score was given to subjects on Day 7 at 21:30 (±30 minutes) during the product use period. The data shown are the means calculated from only those participants with scores in the corresponding category ('-50 to <0', '0' and '>0 to 50').	Data collected on Day 7 at 21:30 (±30 minutes) during the product use period
Summary of Response for Willingness to Use the VERVE® Product Again Bipolar VAS Scores for Cigarettes by Category, Study Group and Study Product (mITT Population)	Summary of subject responses to "Use the Product (VERVE®) Again" Bipolar Visual Analogue Scale (VAS) Scores for the VERVE® test products are presented. The Use the Product Again Bipolar VAS is a 100 mm scale ranging from 0 mm ("Definitely Would Not") to 100 mm ("Definitely Would"). The bipolar score is calculated by subtracting 50 from the original VAS score, then categorizing into three categories: -50 to <0, 0, and >0 to 50. Higher scores are associated with greater willingness to use the VERVE® product again. Mean and standard deviation of the bipolar VAS score per category is shown. The "Use the Product Again" VAS Score was given to subjects on Day 7 at 21:30 (±30 minutes) during the product use period. The data shown are the means calculated from only those participants with scores in the corresponding category ('-50 to <0', '0' and '>0 to 50').	Data collected on Day 7 at 21:30 (±30 minutes) during the product use period

Collaborators and Investigators

• Sponsor: Altria Client Services LLC
• Investigators: Study Director: Georgios D Karles, PhD, Altria Client Services LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2018
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: September 21, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 2, 2018

Study Record Updates

• Last Update Posted (Actual): November 25, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ALCS-RDS-18-04-VRV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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