Comparison of Cigarette Smoking to Dual Use of Cigarettes ... · Study Design 6 Week 1 Week 2 Week 3 Week 4 Screening & Enrollment Visit1% % ad libitum smoking reduce CPD 25% reduce

Comparison of Cigarette Smoking to Dual Use of Cigarettes with Camel Strips®, Camel Sticks®, or Camel SNUS®

Elaine K. Round, Leanne C. Lee, Sheri A. Bowman, Kelly M. Harger, Tracy M. Hefner, Misty M. Mathews, Paul R. Nelson, Angela M. Slater, Mitchell F. Stiles, Michael F. Borgerding R.J. Reynolds Tobacco Company Winston Salem, NC

66th TSRC 9-11 September 2012 Concord, NC

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Outline •  Objective of Studies •  Design of Studies •  Results •  Conclusions

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Objective

•  Evaluate dual use of cigarettes with either Camel Strips, Camel Sticks, or Camel SNUS by adult smokers

–  Product Use –  Mouth Level Exposure (MLE) –  Biomarkers of Exposure –  Subjective Ratings

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Main Inclusion/Exclusion Criteria

•  Males and females age 21-55, inclusive •  Primary tobacco use is cigarette smoking •  Generally healthy as determined by physician •  No active oral lesions •  No history of major health conditions •  Smoke ≥ 7 cigarettes per day (CPD)

for at least 1 year •  Not delaying a decision to quit tobacco use to

participate in study

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Study Overview

•  Each study approved by the RJRT Human Research Review Committee

•  Ambulatory •  Screening Visit

–  Informed consent –  Evaluation of Inclusion/Exclusion Criteria –  Product sampling

•  Four Weekly Test Visits –  Study procedures –  Adverse event monitoring

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Study Design

6

Week 1 Week 2 Week 3 Week 4 Screening & Enrollment

Visit 1

reduce CPD 25% reduce CPD 50% reduce CPD 75% ad libitum smoking

include use of Strips, Sticks, or Camel SNUS

Product Use Log

Snus Pouch Collection

24h Urine Collection

Cigarette Filter Collection

Questionnaire Completion

Visit 4

Visit 3

Visit 2

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Study Products

•  Usual brand (UB) cigarette (provided by subject)

•  One of three smokeless products

–  Camel Strips: Unbranded

Predominantly milled tobacco

~ 0.54 mg nicotine per Strip

–  Camel Sticks: Unbranded

Predominantly milled tobacco

~ 2.56 mg nicotine per Stick –  Camel SNUS: Market tins

~ 600 mg tobacco per pouch

~ 7.33 mg nicotine per pouch

Mean MLE = 1.6 mg per pouch

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Product Use and Ratings

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Reported Product Use By Study

9 *p < 0.05, pairwise comparison with Week 1

*p < 0.05, pairwise comparison with Week 2

0

5

10

15

20

25

30

35

Week 1 Week 2 Week 3 Week 4

Cigare1es Per Day

Cigare1es

0

5

10

15

20

25

30

35

Week 1 Week 2 Week 3 Week 4

Smok

eless P

rodu

cts P

er Day

Smokeless Products

Strips Study S>cks Study Snus Study n=28 n=28 n=32

↓22-‐24%

↓41-‐42%

↓59-‐60% * * *

* * *

* * *

*

* *

*

*

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Product Ratings

10 * p < 0.05, Kendall’s τ test for trend

Strips S>cks Snus n=28 n=28 n=32

0

10

20

30

40

50

60

70

80

90

100

Visit 1 Visit 2 Visit 3 Visit 4

Ra>n

g

Smokeless Product

0

10

20

30

40

50

60

70

80

90

100


Ra>n

g UB Cigare1e

Very Best/ Perfect

Excellent

Very Good

Quite Good

Fairly Good

Very Worst/ Can’t Use At All

Indifferent

Not Very Good Not Good At All

Terrible

Poor

* * * * *

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Mouth Level Exposure

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MLE Per Cigarette

12 *p < 0.05, pairwise comparison with Visit 1

0

0.5

1

1.5

2

2.5


mg/cigare1e

Nico>ne

0

5

10

15

20

25

30


mg/cigare1e

“Tar” *

*


*

*

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Daily MLE from Cigarette Smoking

13 *p < 0.05, pairwise comparison with Visit 1

0

5

10

15

20

25

30

35

40

45


mg/da

y

Nico>ne

0

100

200

300

400

500

600


mg/da

y

“Tar”

* * *

* *

*


*

* * *

* *

* *

* *

*

*

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Total Daily MLE from Dual Use

14 *p < 0.05, pairwise comparison of Visit 1 and Visit 4

0

5

10

15

20

25

30

35

40

45

Visit 1 Visit 4 Visit 1 Visit 4 Visit 1 Visit 4

mg/da

y

Nico>ne

0

500

1000

1500

2000

2500

3000

3500

4000

Visit 1 Visit 4 Visit 1 Visit 4 Visit 1 Visit 4

ng/day

NNK



↓ 12%

↓ 30%

↓ 41%

↓ 56%

↓ 24%

↓ 64%

*

*

*

*

*

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Urinary Biomarkers of Exposure

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All Studies:

•  Nicotine Equivalents

•  NNAL-T

•  3-HPMA Vapor Phase, Cigarette Specific

Particulate Phase, All Products

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-‐40.00% -‐30.00% -‐20.00% -‐10.00% 0.00% 10.00% 20.00% 30.00% 40.00%

Median % Change from Week 1 to Week 4

Strips n=27

S>cks n=24

Snus n=30

* p < 0.05, Week 1 vs. Week 4 (Wilcoxon Signed Rank Test) * 0.05 < p < 0.1, Week 1 vs. Week 4 (Wilcoxon Signed Rank Test)

*

*

*

*

*

3-HPMA

NicEq-T

NNAL-T

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Camel SNUS Study only:

•  NNN-T •  1-OH-Naphthalene

•  NAT-T •  2-OH-Naphthalene

•  NAB-T •  2-OH-Fluorene

•  TSNA-T •  1-OH-Phenanthrene

•  3-Aminobiphenyl •  2-OH-Phenanthrene

•  4-Aminobiphenyl •  3-OH-Phenanthrene

•  2-Aminonaphthalene •  4-OH-Phenanthrene

•  o-Toluidine •  9-OH-Phenanthrene

•  AAMA •  1-OH-Pyrene

•  GAMA

•  S-PMA •  Thiocyanate

•  HMPMA •  CEMA

•  MHBMA •  HEMA

Vapor Phase, Cigarette Specific


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-‐40.00% -‐30.00% -‐20.00% -‐10.00% 0.00% 10.00% 20.00% 30.00% 40.00%

o-‐Toluidine 2-‐OH-‐Naphthalene

GAMA NAB-‐T AAMA

2-‐OH-‐Fluorene 2-‐AN

1-‐OH-‐Naphthalene 3-‐ABP

HMPMA CEMA

3-‐HPMA HEMA SPMA

MHBMA Thiocyanate

Median % Change from W1 to W4 by Sta>s>cal Significance

Additional Urinary Biomarkers – Camel SNUS Study

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p < 0.05

Vapor Phase, Cigarette Specific


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-‐40.00% -‐30.00% -‐20.00% -‐10.00% 0.00% 10.00% 20.00% 30.00% 40.00%

3-‐OH-‐Phenanthrene

NNN-‐T


1-‐OH-‐Pyrene



NNAL-‐T

NicEq-‐T


NAT-‐T

TSNA-‐T

4-‐ABP

Median % Change from W1 to W4 by Sta>s>cal Significance

Additional Urinary Biomarkers – Camel SNUS Study

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0.05 < p < 0.1

p > 0.1


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Conclusions •  Subjects reported a reduction in CPD and switched

to dual use with a smokeless product during study.

•  Statistically significant decreases in ratings of UB cigarettes occurred during dual use with Strips, Sticks, and Camel SNUS.

•  Daily mouth level exposure from cigarettes decreased during dual use.

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Conclusions •  Biomarkers of exposure did not statistically

significantly increase during dual use.

•  In the Camel SNUS study: –  Urinary biomarkers generally decreased during dual use.

–  Biomarkers of all vapor phase constituents statistically significantly decreased.

•  Self-reported product use data are a limitation of ambulatory studies.

•  Studies in which subjects are confined during dual use would allow direct observation of product use and contribute to the understanding of these results.

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Acknowledgements •  Clinical Services

–  Piedmont Medical Research, Winston-Salem, NC –  Bellomy Research Inc., Winston-Salem, NC

•  Cigarette MLE Analyses –  Strips and Snus Studies: Arista Laboratories, Richmond, VA –  Sticks Study: Labstat International ULC, Kitchener, ON –  NNK calibration curve data: Joy Bodnar, RJRT

•  Snus MLE Analyses –  Labstat International ULC, Kitchener, ON

•  Urinary Biomarker Analyses –  ABF Analytisch-Biologisches Forschunglabor GmbH, Munich, Germany

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Thank You

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Documents

Comparison of Cigarette Smoking to Dual Use of Cigarettes ... · Study Design 6 Week 1 Week 2 Week 3 Week 4 Screening & Enrollment Visit1% % ad libitum smoking reduce CPD 25% reduce