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NCT03571724

A Study to Assess Changes in Cigarette Consumption During a Switch to Very Low Nicotine Cigarettes

Completed NA Results posted Last updated 16 September 2020
What this trial tests

NA trial testing Non-Menthol Very Low Nicotine Cigarettes in Tobacco Use in 142 participants. Completed in 8 March 2019.

Timeline
28 June 2018
Primary endpoint
25 January 2019
8 March 2019

Quick facts

Lead sponsor22nd Century Group, Inc.
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposeother
Enrollment142
Start date28 June 2018
Primary completion25 January 2019
Estimated completion8 March 2019
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

22nd Century Group, Inc. — full company profile →

Who can join

Adults 26 to 65, any sex, with Tobacco Use. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cigarettes Per Day Primary · Assessed daily from Week -1 to Week 6; Week -1, Week 2, and Week 6 reported

Primary objective is to measure a change in cigarette consumption behavior before, during and after switching from usual brand to to VLN cigarettes. Subjects will record their cigarette consumption daily in an electronic diary. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).All 142 randomized subjects were included in the ITT population based on product use. Out of these, 71 subjects were included in the PP Population and 71 were excluded. All excluded subjects ha

Week -1
GroupValue95% CI
Very Low Nicotine Mentholated14.75± 6.198
Very Low Nicotine Non-Mentholated17.19± 4.727
Very Low Nicotine Combined15.76± 5.676
Usual Brand Mentholated16.29± 5.809
Usual Brand Non-Mentholated16.80± 4.015
Usual Brand Combined16.55± 4.895
Week 2
GroupValue95% CI
Very Low Nicotine Mentholated15.66± 7.860
Very Low Nicotine Non-Mentholated23.32± 9.717
Very Low Nicotine Combined18.90± 9.341
Usual Brand Mentholated15.47± 4.425
Usual Brand Non-Mentholated16.17± 4.475
Usual Brand Combined15.84± 4.411
Week 6
GroupValue95% CI
Very Low Nicotine Mentholated14.43± 9.435
Very Low Nicotine Non-Mentholated21.20± 8.219
Very Low Nicotine Combined17.98± 9.265
Usual Brand Mentholated14.69± 4.877
Usual Brand Non-Mentholated15.89± 5.356
Usual Brand Combined15.29± 5.092
Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) Secondary · -1 week, and at 2 and 6 weeks.

Total 24 hour urine will be collected to evaluate changes in NNAL (4-methylnitrosamino)-1-3-pyridyl)-1-butanone biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated582.855± 288.3650
VLN Mentholated423.752± 185.6953
VLN Combined502.500± 253.6974
UB Non-Mentholated614.06± 353.9198
UB Mentholated479.979± 203.2470
UB Combined548.658± 294.7134
Week 2
GroupValue95% CI
VLN Non-Mentholated313.911± 176.1390
VLN Mentholated214.139± 131.4077
VLN Combined266.766± 163.6124
UB Non-Mentholated581.039± 312.7864
UB Mentholated458.036± 203.4045
UB Combined521.037± 269.1556
Week 6
GroupValue95% CI
VLN Non-Mentholated377.057± 217.6683
VLN Mentholated240.970± 173.1282
VLN Combined309.833± 207.3562
UB Non-Mentholated614.717± 416.6105
UB Mentholated431.458± 173.9915
UB Combined517.997± 321.7481
Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) Secondary · -1 week, and at 2 and 6 weeks.

Total 24 hour urine will be collected to evaluate changes in NNN before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated20.070± 14.4934
VLN Mentholated12.370± 7.9412
VLN Combined16.181± 12.2224
UB Non-Mentholated22.614± 24.4627
UB Mentholated13.641± 11.1026
UB Combined18.237± 19.4522
Week 2
GroupValue95% CI
VLN Non-Mentholated14.246± 11.6548
VLN Mentholated9.052± 10.2762
VLN Combined11.792± 11.2701
UB Non-Mentholated20.809± 21.2301
UB Mentholated12.024± 9.0103
UB Combined16.523± 16.8430
Week 6
GroupValue95% CI
VLN Non-Mentholated14.803± 11.4754
VLN Mentholated6.382± 4.5544
VLN Combined10.643± 9.6904
UB Non-Mentholated22.095± 25.7769
UB Mentholated9.359± 6.0602
UB Combined15.373± 19.0844
Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) Secondary · -1 week, and at 2 and 6 weeks.

Total 24 hour urine will be collected to evaluate changes in S-PMA (benzene biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated7.144± 5.9255
VLN Mentholated6.561± 3.8833
VLN Combined6.850± 4.9823
UB Non-Mentholated7.935± 3.8120
UB Mentholated8.239± 7.3290
UB Combined8.083± 5.7274
Week 2
GroupValue95% CI
VLN Non-Mentholated8.160± 7.8142
VLN Mentholated6.734± 4.7617
VLN Combined7.486± 6.5560
UB Non-Mentholated7.561± 3.7582
UB Mentholated7.731± 5.9223
UB Combined7.644± 4.8713
Week 6
GroupValue95% CI
VLN Non-Mentholated7.282± 6.4350
VLN Mentholated5.589± 3.6334
VLN Combined6.446± 5.2792
UB Non-Mentholated7.261± 4.4329
UB Mentholated6.845± 5.2829
UB Combined7.042± 4.8353
Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) Secondary · -1 week, and at 2 and 6 weeks.

Total 24 hour urine will be collected to evaluate changes in 3-HPMA (acrolein biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated1795.719± 708.6089
VLN Mentholated1644.113± 500.1249
VLN Combined1719.151± 613.8453
UB Non-Mentholated1910.675± 772.7715
UB Mentholated1520.921± 605.2480
UB Combined1720.551± 715.1892
Week 2
GroupValue95% CI
VLN Non-Mentholated1706.862± 901.3990
VLN Mentholated1204.530± 543.2655
VLN Combined1469.496± 790.9739
UB Non-Mentholated1710.747± 732.7759
UB Mentholated1329.844± 319.7909
UB Combined1524.940± 595.1580
Week 6
GroupValue95% CI
VLN Non-Mentholated1481.693± 694.6765
VLN Mentholated1035.064± 475.3512
VLN Combined1261.069± 634.0203
UB Non-Mentholated1815.382± 828.3606
UB Mentholated1336.103± 297.2953
UB Combined1562.429± 673.6060
Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) Secondary · -1 week, and at 2 and 6 weeks.

Total 24 hour urine will be collected to evaluate changes in 1-OHP before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated334.920± 167.7463
VLN Mentholated315.203± 160.6678
VLN Combined324.962± 163.6689
UB Non-Mentholated314.736± 90.9545
UB Mentholated316.566± 140.5579
UB Combined315.629± 116.2823
Week 2
GroupValue95% CI
VLN Non-Mentholated262.756± 157.8692
VLN Mentholated214.010± 117.020
VLN Combined239.722± 141.4377
UB Non-Mentholated289.071± 97.7694
UB Mentholated263.305± 101.9363
UB Combined276.502± 99.4242
Week 6
GroupValue95% CI
VLN Non-Mentholated278.998± 178.6065
VLN Mentholated203.396± 122.0693
VLN Combined241.652± 157.0509
UB Non-Mentholated299.312± 118.7805
UB Mentholated274.171± 128.5495
UB Combined286.043± 122.9241
Biomarkers of Exposure - Total Nicotine Equivalents Secondary · -1 week, and at 2 and 6 weeks.

Total 24 hour urine will be collected to evaluate changes in total nicotine equivalents before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated17.511± 6.1103
VLN Mentholated15.885± 5.3291
VLN Combined16.690± 5.7580
UB Non-Mentholated17.732± 6.3013
UB Mentholated15.928± 5.9611
UB Combined16.852± 6.1291
Week 2
GroupValue95% CI
VLN Non-Mentholated5.404± 4.5528
VLN Mentholated3.616± 3.5530
VLN Combined4.559± 4.1858
UB Non-Mentholated16.962± 6.2675
UB Mentholated15.279± 4.7106
UB Combined16.141± 5.5594
Week 6
GroupValue95% CI
VLN Non-Mentholated9.150± 6.1240
VLN Mentholated6.800± 5.2118
VLN Combined7.989± 5.7792
UB Non-Mentholated17.530± 7.3994
UB Mentholated14.418± 5.5176
UB Combined15.888± 6.5703
Biomarkers of Exposure - Carboxyhemoglobin (COHb) Secondary · Week -1, and at 2 and 6 weeks.

Blood will be drawn to evaluate COHb before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).

Week -1
GroupValue95% CI
VLN Non-Mentholated6.20± 1.801
VLN Mentholated5.69± 1.526
VLN Combined5.95± 1.680
UB Non-Mentholated5.25± 1.294
UB Mentholated5.41± 1.322
UB Combined5.33± 1.294
Week 2
GroupValue95% CI
VLN Non-Mentholated7.10± 2.794
VLN Mentholated5.55± 2.167
VLN Combined6.36± 2.618
UB Non-Mentholated5.40± 1.206
UB Mentholated5.59± 2.060
UB Combined5.49± 1.659
Week 6
GroupValue95% CI
VLN Non-Mentholated5.97± 1.930
VLN Mentholated4.63± 1.898
VLN Combined5.31± 2.019
UB Non-Mentholated5.56± 1.323
UB Mentholated4.61± 1.259
UB Combined5.07± 1.361
Biomarkers of Exposure -Cotinine Secondary · Week -1, and at 2 and 6 weeks.

Blood will be drawn to evaluate cotinine levels before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.

Week -1
GroupValue95% CI
UB Mentholated242.0± 111.1681285
UB Non-Mentholated221.4± 85.32850957
Week 2
GroupValue95% CI
VLN Non-Mentholated58.8± 58.5318519
VLN Mentholated58.7± 60.58382526
UB Mentholated223.9± 100.5596713
UB Non-Mentholated195.8± 77.043868
Week 6
GroupValue95% CI
VLN Non-Mentholated102.0± 76.3105523
VLN Mentholated110.1± 102.5119239
UB Mentholated207.2± 81.7796209
UB Non-Mentholated187.7± 71.86818497
Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) Secondary · Week -1, and at 2 and 6 weeks.

Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of C-max at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.

Week -1
GroupValue95% CI
UB Non-Mentholated13.28± 5.9925
UB Mentholated12.98± 5.3932
Week 2
GroupValue95% CI
VLN Non-Mentholated0.3264± 0.15367
VLN Mentholated0.3561± 0.20204
Week 6
GroupValue95% CI
VLN Non-Mentholated0.4026± 0.15292
VLN Mentholated0.3259± 0.16294
Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) Secondary · Week -1, and at 2 and 6 weeks.

Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of T-Max at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.

Week -1
GroupValue95% CI
UB Mentholated13.60± 5.2610
UB Non-Mentholated0.1408± 0.041525
Week 2
GroupValue95% CI
VLN Non-Mentholated0.1154± 0.040675
VLN Mentholated0.1430± 0.063681
Week 6
GroupValue95% CI
VLN Non-Mentholated0.1446± 0.084195
VLN Mentholated0.2895± 0.43017
Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) Secondary · Week -1, and at 2 and 6 weeks.

Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of AUC at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.

Week -1
GroupValue95% CI
UB Mentholated13.60± 5.2610
UB Non-Mentholated13.18± 4.0648
Week 2
GroupValue95% CI
VLN Non-Mentholated0.2006± 0.19107
VLN Mentholated0.2264± 0.20588
Week 6
GroupValue95% CI
VLN Non-Mentholated0.2620± 0.15446
VLN Mentholated0.2348± 0.20330

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected after the start of Week 1 product use through follow-up call at Week 7.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Non-Menthol Very Low Nicotine Cigarettes
Serious: 1/50 (2%)
Deaths: 0/50
Menthol Very Low Nicotine Cigarettes
Serious: 0/50 (0%)
Deaths: 0/50
Usual Brand Non-Metholated
Serious: 0/22 (0%)
Deaths: 0/22
Usual Brand Metholated
Serious: 0/20 (0%)
Deaths: 0/20

Serious adverse events (1 terms)

ReactionSystemNon-Menthol Very Low Nicot…Menthol Very Low Nicotine …Usual Brand Non-MetholatedUsual Brand Metholated
Subarachnoid haemorrhageInjury, poisoning and procedural complications————
Other adverse events (2 terms — click to expand)

ReactionSystemNon-Menthol Very Low Nicot…Menthol Very Low Nicotine …Usual Brand Non-MetholatedUsual Brand Metholated
HeadacheNervous system disorders————
IrritabilityPsychiatric disorders————

Most-reported serious reactions: Subarachnoid haemorrhage.

Data from ClinicalTrials.gov NCT03571724 adverse events section.

Sponsor's own description

This study evaluates the impact of switching from usual brand cigarettes to very low nicotine cigarettes on cigarette consumption, smoking behavior, and biomarkers of exposure.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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