Current Smoking Cessation Treatment

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Current Smoking Cessation Treatment

• ? ? ?
• ?????????????
• ??????????????

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• 2007?????????,???????500??????,??6.5??????????ht
  tp//www.who.int/tobacco/communications/events/wnt
  d/2007/en/index.html

• ???,?????????????,?????????????????Annual
  smoking-attributable mortality, years of
  potential life lost, and productivity
  losses--United States, 1997-2001. MMWR Morb
  Mortal Wkly Rep 2005 54625
• ????,????????????????????? Center for Disease
  Control and Prevention Cigarette smoking among
  adults 2004

3

• ???????????????300???????????????8.5?,?????????
  ?????(???????,2002)
• 1994??????8,161????1,216?????????,????????????13.9
  ?3.3,????????????????Liaw KM, Chen CJ .
  Mortality attributable to cigarette smoking in
  Taiwana 12-year follow up study. Tob Control
  19987 141-8.
• ?????????18,800???????????(????,2005)

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Tobacco Use

• Global epidemic (WHO)
• 1.3 billion smokers worldwide
• 5 million tobacco-related deaths annually
• Main lethal outcomeslung cancer, CHD, chronic
  lung disease, stroke

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METHODS FOR CESSATION

• Pharmacologic
• Nonparmacologic
• Combined nonpharmacologic and pharmacologic
  therapy

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Nonpharmacologic Treatment for Smoking Cessation

• Physician counseling Simple physician
  advice to quit can increase rates of smoking
  cessation in a general population. Advice
  combined with a personalized health message
  further improves rates of quitting. In addition,
  patients informed of an abnormal pulmonary
  function test have increased likelihood of
  quitting.

• Silagy, C, Lancaster, T, Stead, L, et al.
  Nicotine replacement therapy for smoking
  cessation. Cochrane Database Syst Rev 2004
  CD000146

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????
????????
??????? ??????? (Ask)
????
???
????
???? (Advice)
??/?? ?????? (Primary prevention)
?????? (Relapse prevention)
??????? (Assess)
????
??? ????(Assist)
????(5Rs)
?????????? ???????????? ????????????? ?????????? ?
????
?? ??????????? ?????? ?????? ?????????? ?????????
????(Arrange follow up) ????????????
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ABC guideline(NZ)

• A- Ask
• B- Brief advise
• C- Cessation support

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Pharmacotherapy for Smoking Cessation

• Nicotine replacement therapy1
• Recommended first line therapy
• Long acting
• Patch
• Short acting
• Gum
• Inhaler
• Nasal spray
• Sublingual tablets/lozenges
• Bupropion1
• Recommended first-line therapy (WHO, US, Europe,
  UK)2
• Nortriptyline1
• Recommended second-line therapy (WHO, US)2

WHO World Health Organization.1. Henningfield
JE et al. CA Cancer J Clin. 200555281-299. 2.
Hughes JR et al. Nicotine Tob Res.
20057491499.
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Efficacy of Nicotine Replacement Therapy (NRT)1,2
Comparison N Trials N Participants Pooled OR (95 CI)
Gum 52 17,783 1.66 (1.521.81)
Patch 37 16,691 1.81 (1.632.02)
Nasal spray 4 887 2.35 (1.633.38)
Inhaler 4 976 2.14 (1.443.18)
Tablets/lozenges 4 2739 2.05 (1.622.59)
Combination vs single 7 3202 1.42 (1.141.76)
Any NRT vs control 103 39,503 1.77 (1.661.88)
1. Silagy c et al. Cochrane Database Syst Rev.
2004(3)CD000146. 2. Stead L, Lancaster T. Int J
Epidemiol. 20053410011003.
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Antidepressants for Smoking Cessation
Comparison N Trials N Participants Pooled OR (95 CI)
Bupropion alone vs placebo 19 6443 2.06 (1.772.40)
Bupropion plus nicotine patch vs placebo 2 728 1.60 (1.092.34)
All bupropion vs placebo 21 7171 1.99 (1.732.30)
Nortriptyline alone vs placebo 4 703 2.79 (1.704.59)
Nortriptyline plus nicotine patch vs placebo 2 318 1.53 (0.902.61)
All nortriptyline vs placebo 6 1021 2.14 (1.493.06)

• Limited or no evidence of long-term benefit with
  other antidepressants, including fluoxetine,
  sertraline, paroxetine, moclobemide, and
  venlafaxine,

Hughes JR et al. Cochrane Database Syst Rev.
2004(4)CD000031.
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Long-Term Quit Rates Highest With Combination
Pharmacotherapyand Behavioral Support
Behavior Therapy Brief Advice No Therapy
Medication 30 20 10
No Medication or placebo 15 10 5
Hughes JR. CA Cancer J Clin. 200050143-151.
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????????????6?????????????
??? ??????? ?????
???? 18,415 8.06 28.42
???? 189,714 83.01 21.52
??? 12,537 5.49 20.33
??? 4,355 1.91 20.00
??? 3,528 1.54 34.81
?? 228,549 100 22.42
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New Pharmacotherapy

• Varenicline (Champix)
• Approved for use in treating nicotine dependence
  by FDA in May 2006
• Rimonabant (Acomplia)
• For treating obesity and tobacco addiction,
  approved in UK
• Nicotine vaccine
• Phase II/III trials

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Varenicline (???)

• ?????? Partial Agonist
• ????????,?????????????????????

Varenicline
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Varenicline (???)

• Champix?????????????????????????,?Champix?????????
  ????????????????,???????????????,??????????????.
• Champix???????????,??Champix???????????????,??????
  ?????????,????????.

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Varenicline (???)

• Champix?????????????????????????
• Champix???????24??,varenicline???????,?92????????
  ?,????????,??,??,?????????.
• ???Champix?????????????,??Bupropion????????

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Studies I II Adverse Events
Most Frequent AEs (Varenicline)
Study I Study I Study I Study I Study I Study I Study II Study II Study II Study II Study II Study II
V N349 V N349 Z N329 Z N329 P N344 P N344 V N343 V N343 Z N340 Z N340 P N340 P N340
n () n () n () n () n () n ()
NAUSEA Mild Moderate Severe 98 70 26 2 (28.1) (71.4) (26.5) (2.0) 41 27 12 2 (12.5) (65.9) (29.3) (4.9) 29 22 5 2 (8.4) (75.9) (17.2) (6.9) 101 72 25 5 (29.4) (71.3) (23.8) (5.0) 25 14 10 1 (7.4) (56.0) (40.0) (4.0) 33 30 3 0 (9.7) (90.9) (9.1) (0)
HEADACHE 54 (15.5) 47 (14.3) 42 (12.2) 44 (12.8) 27 (7.9) 43 (12.6)
ABNORMAL DREAMS 36 (10.3) 18 (5.5) 19 (5.5) 45 (13.1) 20 (5.9) 12 (3.5)
FLATULENCE 20 (5.7) 14 (4.3) 10 (2.9) 20 (5.8) 7 (2.1) 8 (2.4)
CONSTIPATION 19 (5.4) 23 (7.0) 13 (3.8) 31 (9.0) 22 (6.5) 5 (1.5)
Values may not total 100 due to rounding
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Varenicline Phase 3 Program Conclusions

• Odds of quitting with varenicline
• Quadrupled compared with placebo
• Doubled compared with Zyban

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Presentation for A3051045
A 12-WEEK, DOUBLE-BLIND, PLACEBO-CONTROLLED,
MULTICENTER STUDY WITH FOLLOW-UP EVALUATING THE
SAFETY AND EFFICACY OF VARENICLINE TARTRATE 1 MG
BID FOR SMOKING CESSATION
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A3051045 Study Design

• 13 Clinic visits- treatment BL, wks 1(TQD),
  2, 3, 4, 6, 8, 10, 12
• follow-up wks
  13, 16, 20, 24

• DURING THE NON-TREATMENT PHASE
• There is no need to capture an AE unless it is
  thought to be due to study drug by investigator
• Document only new medications begin utilized by
  the subject (Self initiated post smoking
  cessation) as aids to smoking cessation

Pfizer Confidential
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Trial Objectives

• Primary Objective
• Compare 12 weeks of treatment with
  varenicline 1mg bid to placebo for smoking
  cessation.
• Primary Endpoint will be the 4 week
  CQR(continuous quit rate) for Weeks 9-12
• Secondary Objectives
• Compare 12 weeks of treatment with varenicline to
  placebo for smoking cessation efficacy at Week 24
• Compare varenicline to placebo for effects on
  craving, withdrawal, and reward
• Summarize safety data for 12 weeks of treatment
  with either varenicline or placebo

Pfizer Confidential
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Demography and Baseline Characteristics
Varenicline N126 Placebo N124
Male N () Female N () 107 (84.9) 19 (15.1) 115 (92.7) 9 (7.3)
Age, Years, Mean (SD) Range 39.7 (9.3) 21 - 62 40.9 (11.1) 23 - 73
Cigarettes per day (in past month) Range 23.4 10 - 60 22.7 10 - 60
No. Years Smoked Range 20.2 3 - 45 22.1 3 - 52
Previous Quit Attempts None N () One N () 2 or More N () 61 (48.4) 42 (33.3) 23 (18.3) 67 (54.0) 27 (21.8) 30 (24.2)
FTND Mean (SD) 5.21 (2.35) 5.00 (2.26)
Pfizer Confidential
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Demography and Baseline CharacteristicsTaiwan
Varenicline N63 Placebo N62
Male N () Female N () 50 (79.4) 13 (20.6) 59 (90.3) 6 (9.7)
Age, Years, Mean (SD) Range 38.7 (9.9) 21 - 62 40.0 (11.1) 23 - 64
Cigarettes per day (in past month) Range 24.6 10 - 60 22.3 10 - 60
No. Years Smoked, Mean Range 19.3 3 - 41 21.6 4 - 50
Previous Quit Attempts None N () One N () 2 or More N () 38 (60.3) 18 (28.6) 7 (11.1) 40 (64.5) 16 (25.8) 6 (9.6)
FTND Mean (SD) 5.83 (2.39) 5.02 (2.23)
Pfizer Confidential
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Total, Taiwan Korea 9-12weeks
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Total, Taiwan Korea 9-24weeks
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Varenicline ?????????
QSU-Brief Total Craving Score Repeated
Measures Analysis Effect size -0.29 P-value vs.
placebo 0.0005
MNWS Urge to Smoke Repeated Measures Analysis
Effect size -0.42 P-value vs. placebo lt0.0001
MNWS (Minnesota Nicotine Withdrawal Scale )
QSU-Brief Brief Questionnaire of Smoking Urges )
Pfizer Confidential
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?????????
?? Study A3051045 Study A3051045 Taiwan All Causality Taiwan All Causality
?? Varenicline N126 Placebo N124 Varenicline N63 Placebo N62
???? ?? 43.7 11.3 36.5 8.1
???? ?? 7.1 2.4 9.5 0.0
???? ?? 4.8 4.0 3.2 0.0
???? ???? 4.8 0.0 3.2 0.0
???? ?? 4.0 3.2 4.8 3.2
???? ?? 15.1 13.7 14.3 22.6
???? ?? 5.6 2.4 7.9 3.2
???? ?? 5.6 0.8 5.6 2.4
???? ???? 4.8 2.5 9.5 3.2
???? ???? 7.9 6.5 14.3 9.7
???? ???? 4.8 1.6 6.3 0.0
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????????
?? Study A3051045 Study A3051045 Taiwan Taiwan
?? Varenicline N126 ??? N124 Varenicline N63 ??? N62
???? ?? 42.9 11.3 34.9 8.1
???? ?? 4.8 1.6 4.8 0.0
???? ???? 4.8 0.0 3.2 0.0
???? ?? 9.5 7.3 9.5 11.3
???? ?? 5.6 0.8 - -
???? ???? 4.0 2.4 7.9 3.2
Pfizer Confidential
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Change in Body Weight Baseline to Week 12
Varenicline Placebo All Subjects n117 n119 Mea
n Change Kg (SE) 1.17 (0.20) 0.66
(0.16) Cessators n71 n40 Mean Change Kg
(SE) 1.29 (0.28) 1.59 (0.27)
Cessators subjects who did not smoke in Weeks
9-12
Pfizer Confidential
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????(2007.1011) case78
?????????????
?? 42? 53.8
?? 36? 46.2
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36? 46.2
?? 42? 53.8
25? 32.1
12? 15.4
5? 6.4
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????(2007.1011) case78
P0.79
?? 68? 87.2 ?? 31? 45.6
?? 10? 12.8 ?? 5 ? 50
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????????(2007.1011) case78
18
15
15
17
12
10
9
4
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??????VGHKS case78
??/?? p
?? 1 1.3 1 / 0
???? 0 0 -
?????? 0 0 -
????/?(??) 0 0 -
???? 0 0 -
???? 13 16.7 12 / 1 0.001
????? 4 5.1 2 / 2
?? 1 1.3 1 / 0
?? 15 19.2 12 / 3 0.01
?? 2 2.6 0 / 2 0.16
???? 7 9.0 5 / 2 0.43
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Independent T test p?????
????????? ?? ?? ???
??? ?? 42 27.9 ?
?? 36 26.7?
?? ?? 42 22.0 ?
?? 36 23.6?
?????FTND ?? 42 6.8?
?? 36 6.9 ?
champix???? ?? 42 4.1 ?
?? 36 4.1 ?
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• The pooled odds ratio (OR) for continuous
  abstinence at 12 months for varenicline versus
  placebo was 3.22 (95 CI 2.43 to 4.27).
• The pooled OR for varenicline versus bupropion
  was 1.66 (95 CI 1.28 to 2.16).
• The main adverse effect of varenicline was
  nausea, which was mostly at mild to moderate
  levels and usually subsided over time.

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• There is a need for independent trials of
  varenicline versus placebo, to test the early
  findings.
• There is also a need for direct comparisons with
  nicotine replacement therapy, and for further
  trials with bupropion, to establish the relative
  efficacy of the treatments

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Varenicline (Chmapix, Chantix)

• The drug has been prescribed to 4 million people
  in the United States since approval in 2006
• Pfizer reported third-quarter (2007) sales of
  241 million for Chantix, up from 33 million a
  year earlier.

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FDA issued an early warning

• In November 2007, the FDA issued an early warning
  after receiving reports of suicidal thoughts and
  behavior, and at least one death, potentially
  linked to the medication.
• Typically only a fraction of adverse events are
  reported to the FDA.
• New York-based Pfizer said no causal relationship
  has been established between the drug and the
  behaviors, but in some cases, an association
  could not be ruled out.

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EU Wants New Warnings on Champix

• LONDON (Reuters) Dec 14 - The European Medicines
  Agency said on Friday that linked to Pfizer Inc's
  new smoking cessation pill.
• Pfizer has been asked to submit changes to the
  marketing information for the product -- sold as
  Champix in Europe and Chantix in the United
  States -- before December 19.

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Pfizer Anti-Smoking Drug Behavior Warning Pushed
Up

• WASHINGTON (Reuters) Jan 18 - An anti-smoking
  drug sold by Pfizer Inc will including
  agitation, depression and suicidal behavior
• Serious neuropsychiatric symptoms including
  changes in behavior, agitation, depressed mood,
  suicidal ideation and suicidal behavior

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Thanks for your attention