PMID- 17692720
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20221207
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 29
IP  - 6
DP  - 2007 Jun
TI  - Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine 
      receptor partial agonist, in a 12-week, randomized, placebo-controlled, 
      dose-response study with 40-week follow-up for smoking cessation in Japanese 
      smokers.
PG  - 1040-56
AB  - BACKGROUND: Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor 
      partial agonist, has been developed specifically for smoking cessation. In Japan, 
      39.3% of men smoke and this is a major public health concern. OBJECTIVE: The 
      primary objective of this study was to evaluate the efficacy and dose-response 
      relationship of varenicline in Japanese smokers. METHODS: In this double-blind, 
      placebo-controlled, randomized, parallel-group study, subjects were randomized to 
      receive varenicline at 0.25 mg BID, 0.5 mg BID, 1 mg BID, or placebo for 12 weeks 
      followed by a 40-week, nontreatment follow-up phase. The primary efficacy 
      variable was the continuous abstinence rate (CAR), defined as no reported smoking 
      (not even a puff) or other nicotine use and confirmed by end-expiratory carbon 
      monoxide level <or=10 ppm, during the last 4 weeks of treatment (weeks 9-12). 
      Secondary end points included CARs for weeks 9-24 and 9-52. Craving, withdrawal, 
      and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal 
      Scale, the Brief Questionnaire on Smoking Urges, and the modified Cigarette 
      Evaluation Questionnaire. The tolerability of varenicline was also evaluated. 
      RESULTS: Of 618 subjects who received treatment, 515 (83.3%) were classified as 
      nicotine dependent (scoring >or=5 on the Tobacco Dependence Screener), and 
      constituted the primary analysis group. Of these, 385 (74.8%) subjects were male, 
      and the mean age was within the range of 39.0 to 40.2 years. Across treatment 
      groups, subjects claimed to have smoked a mean of 23.1 to 24.9 cigarettes per day 
      in the preceding 30 days, and the mean score on the Fagerstrom Test for Nicotine 
      Dependence was within the range from 5.4 to 5.7. The CAR for weeks 9-12 was 
      significantly higher for all doses of varenicline compared with placebo (39.5% 
      [51/129]). The highest CAR of 65.4% (85/130) was achieved with varenicline 1 mg 
      BID (odds ratio [OR] [95% CI] = 2.98 [1.78-4.99]; P < 0.001). The CAR for weeks 
      9-52 was significantly greater for varenicline 1 mg BID than placebo (34.6% 
      [45/130] vs 23.3% [30/129]; OR [95% CI] = 1.81 [1.04-3.17]; P = 0.036). The CARs 
      for weeks 9-24 at 0.25, 0.5, and 1 mg BID were 33.6% (43/128), 35.2% (45/128), 
      37.7% (49/130), and for weeks 9-52 at 0.25 and 0.5 mg BID were 27.3% (35/128) and 
      28.9% (37/128) but failed to reach significance versus the placebo (29.5% 
      [38/129] for weeks 9-24 and 23.3% [30/129] for weeks 9-52). Treatment-emergent 
      adverse events (AEs) were more prevalent among varenicline-treated subjects 
      (79.1% [121/153] at 0.25 mg BID, 80.6% [125/155] at 0.5 mg BID, and 80.1% 
      [125/156] at 1 mg BID) than placebo subjects (71.4% [110/154]). The 3 most 
      prevalent AEs at varenicline 1 mg BID were nasopharyngitis (35.9% [56/156]), 
      nausea (24.4% [38/156]), and headache (10.3% [16/156]), all of which were of mild 
      or moderate intensity. Nausea was the only AE that appeared dose related (7.2% 
      [11/153] at 0.25 mg BID, 9.7% [15/155] at 0.5 mg BID, and 24.4% [38/156] at 1 mg 
      BID) versus placebo (7.8% [12/154]). CONCLUSIONS: Varenicline was associated with 
      dose-dependent improvement in smoking abstinence rates during the last 4 weeks of 
      treatment and in the longer term over 40 weeks of nontreatment follow-up. The 
      dose associated with the highest efficacy was varenicline 1 mg BID.
FAU - Nakamura, Masakazu
AU  - Nakamura M
AD  - Department of Health Promotion and Education, Osaka Medical Center for Health 
      Science and Promotion, Osaka, Japan. nakamura@kenkoukagaku.jp
FAU - Oshima, Akira
AU  - Oshima A
FAU - Fujimoto, Yoko
AU  - Fujimoto Y
FAU - Maruyama, Nami
AU  - Maruyama N
FAU - Ishibashi, Taro
AU  - Ishibashi T
FAU - Reeves, Karen R
AU  - Reeves KR
LA  - eng
SI  - ClinicalTrials.gov/NCT00139750
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Benzazepines)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic receptor alpha4beta2)
RN  - W6HS99O8ZO (Varenicline)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Asian People
MH  - Benzazepines/adverse effects/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Nicotinic Agonists/adverse effects/*therapeutic use
MH  - Quinoxalines/adverse effects/*therapeutic use
MH  - Receptors, Nicotinic/*drug effects
MH  - Smoking Cessation/*methods
MH  - Treatment Outcome
MH  - Varenicline
EDAT- 2007/08/19 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/04/26 00:00 [accepted]
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - S0149-2918(07)00171-3 [pii]
AID - 10.1016/j.clinthera.2007.06.012 [doi]
PST - ppublish
SO  - Clin Ther. 2007 Jun;29(6):1040-56. doi: 10.1016/j.clinthera.2007.06.012.