Clinical trial NCT03692078: A Study to Evaluate Changes in Smokers Using Oral Tobacco-derived Nicotine Products.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Use
Lead sponsor: Altria Client Services LLC
Sponsor class: INDUSTRY
First posted: 2018-10-02
Enrollment: 231
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Summary of Urine Total NNAL Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of Urine Total NNAL Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
Secondary outcomes:
measure: Summary of NNN Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of NNN Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of Nicotine Equivalents Amount Excreted and Absolute Change From Baseline (mg/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of Nicotine Equivalents Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 2-AN Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 2-AN Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 4-ABP Amount Excreted and Absolute Change From Baseline (ng/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 4-ABP Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of HEMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of HEMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of CEMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of CEMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of S-PMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of S-PMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 3-HMPMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 3-HMPMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 3-HPMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 3-HPMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 2-HPMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 2-HPMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of AAMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of AAMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of GAMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of GAMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 2-MHBMA Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 2-MHBMA Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 2-OHFLe Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 2-OHFLe Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 2-Naphthol Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 2-Naphthol Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 1-OHPhe Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 1-OHPhe Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of 1-OHP Amount Excreted and Absolute Change From Baseline (ug/24 Hour) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of 1-OHP Amount Excreted Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of Urine Mutagenicity and Absolute Change From Baseline (Revertants/24 Hours) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of Urine Mutagenicity Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Summary of Whole Blood COHb and Absolute Change From Baseline (% Saturation) by Study Group and Study Day (mITT Population)
timeFrame: Baseline (Day -1), Day 5 and Day 7
measure: Summary of Whole Blood COHb Percent Change From Baseline (%) by Study Group and Study Day (mITT Population)
timeFrame: Day 5 and Day 7
measure: Cigarette Consumption by Study Group and Study Day (mITT Population)
timeFrame: Day -1 and Day -2 (Baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
measure: Summary of VERVE® Product Usage by Study Group and Study Day (mITT Population)
timeFrame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
measure: Summary of VERVE® Product Use Duration by Study Group and Study Day (mITT Population)
timeFrame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
measure: Summary of Total Duration (Min) of VERVE® Product Per Day by Study Group and Study Day (mITT Population)
timeFrame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7
measure: Summary of Response for Willingness to Use Cigarettes Again Bipolar VAS Scores for Cigarettes by Category, Study Group and Study Product (mITT Population)
timeFrame: Data collected on Day 7 at 21:30 (±30 minutes) during the product use period
measure: 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)
timeFrame: Data collected on Day 7 at 21:30 (±30 minutes) during the product use period
Other outcomes:
Locations:
city: Springfield
country: United States
facility: QPS Bio-Kinetic Clinical Applications, LLC
state: Missouri
city: Neptune
country: United States
facility: Inflamax - Hill Top Research
state: New Jersey
Study officials:
affiliation: Altria Client Services LLC
name: Georgios D Karles, PhD
role: STUDY_DIRECTOR
References: