A Study To Evaluate The Efficacy And Safety Of Varenicline Compared To Placebo For Smoking Cessation Through Reduction

A Phase 4, Multi-National, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of Varenicline Compared To Placebo For Smoking Cessation Through Reduction

This study will determine whether varenicline is safe and helps people to quit smoking through reduction when they are not willing/able to make an abrupt quit attempt.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Varenicline Tartrate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1510
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Maroubra, New South Wales, Australia, 2035
      • Australian Clinical Research Network
  • Queensland
    • Carina Heights, Queensland, Australia, 4152
      • Brisbane South Clinical Research Centre
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Malvern, Victoria, Australia, 3145
      • Emeritus Research
• Canada
  • Quebec, Canada, G1V 4M6
    • Clinique des Maladies Lipidiques de Quebec (CMLQ)
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 1T4
      • Office of Dr. Ronald Collette
    • Vancouver, British Columbia, Canada, V5K 1K3
      • James K. Lai, MD., Inc.
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
      • White Hills Medical Clinic
  • Ontario
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research
    • Toronto, Ontario, Canada, M3H 5S4
      • Canadian Phase Onward Inc.
• Czech Republic
  • Brno, Czech Republic, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Brno, Czech Republic, 602 00
    • SurGal Clinic s.r.o.
  • Liberec 1, Czech Republic, 460 01
    • Krajska nemocnice Liberec a.s., Plicni oddeleni
  • Ostrava 1, Czech Republic, 728 80
    • Mestska nemocnice Ostrava, Plicni oddeleni
  • Praha 2, Czech Republic, 120 00
    • Vseobecna fakultni nemocnice v Praze
  • Praha 2, Czech Republic, 120 00
    • Vseobecna fakultni nemocnice v Praze, III. interni klinika
  • Praha 6, Czech Republic, 169 02
    • Ústřední Vojenská Nemocnice Praha
• Egypt
  • Alexandria, Egypt
    • Alexandria University
  • Cairo, Egypt
    • Ain Shams University Hospital
  • El Fayoum, Egypt
    • El Fayoum university hospital
• Germany
  • Berlin, Germany, 13125
    • Klinische Forschung Berlin-Buch GmbH
  • Berlin, Germany, 10787
    • Klinische Forschung Berlin
  • Goettingen, Germany, 37075
    • Universitaetsklinikum Goettingen Zentrum Innere Medizin Abteilung Kardiologie und Pneumologie
  • Goettingen, Germany, 37075
    • Universitaetsklinikum Goettingen, Zentrum Innere Medizin, Abteilung Kardiologie und Pneumologie
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg GmbH
  • Leipzig, Germany, 04109
    • Medamed- Studienambulanz
  • Neuss, Germany, 41460
    • FOCUS Clinical Drug Development GmbH
• Japan
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Kubo Clinic
    • Yokohama, Kanagawa, Japan
      • Nagatsuta family clinic
    • Yokohama, Kanagawa, Japan
      • Sakakibara Clinic, Wakaumekai Medical Corporation
  • Saitama
    • Tokorozawa, Saitama, Japan
      • Saino Clinic
  • Tokyo
    • Edogawa-ku, Tokyo, Japan
      • Tajima Clinic
    • Hachiouji, Tokyo, Japan
      • Hachiouji Junkanki clinic
• Mexico
  • D.f.
    • Mexico, D.f., Mexico, 14050
      • Centro Respiratorio de Mexico S.C.
    • Mexico, D.f., Mexico, 06700
      • Arke Estudios Clinicos S.A.
  • Michoacan
    • Morelia, Michoacan, Mexico, 58249
      • Clinica de Enfermedades Cronicas y de Procedimientos Especiales S.C.
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64620
      • Centro de Estudios Clinicos y Especialidades Medicas SC
• Taiwan
  • Kaohsiung, Taiwan, 813
    • Kaohsiung Veterans General Hosptial
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital, Department of Family Medicine
  • Taoyuan County
    • Kweishan Town, Taoyuan County, Taiwan, 333
      • Chang Gung Medical Foundation-Linkou Branch
• United Kingdom
  • London, United Kingdom, SE23 1HU
    • The Jenner Practice
  • Cornwall
    • Fowey, Cornwall, United Kingdom, PL23 1DT
      • Enchord Limited
    • Penzance, Cornwall, United Kingdom, TR18 4JH
      • The Alverton Practice
  • Devon
    • Plymouth, Devon, United Kingdom, PL5 3JB
      • Knowle House Surgery
  • Glasgow
    • Castlemilk, Glasgow, United Kingdom, G45 9EW
      • Castlemilk Health Centre
  • Llanelli
    • Dafen, Llanelli, United Kingdom, SA14 8QF
      • Prince Philip Hospital
  • Wilts
    • Chippenham, Wilts, United Kingdom, SN14 8GT
      • Hathaway Medical Centre
• United States
  • California
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, P.C.
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5910
      • University of Nebraska Medical Center
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • CRI Worldwide, LLC
    • Willingboro, New Jersey, United States, 08046
      • Clinical Research Integrity(CRI) Worldwide, LLC
  • New York
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials, L.P.
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
    • Fort Worth, Texas, United States, 76135
      • HealthFirst Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female cigarette smokers over the age of 18 years who are not willing/able to quit smoking within the next month but who are willing to attempt to reduce their smoking to work toward a quit attempt within the next 3 months.
• Subjects must have smoked an average of at least 10 cigarettes per day during the past year and during the month prior to the screening visit, with no continuous period of abstinence greater than 3 months in the past year and who have an exhaled carbon monoxide (CO) >10 ppm at screening.
• Subjects with mild to moderate depression or anxiety may be included if their condition is stable.

Exclusion Criteria:

• Subjects with a history of a suicide attempt or any suicidal behavior in the past two years.
• Subjects with severe depression or anxiety.
• Subjects with psychosis, panic disorder, bipolar disorder, post traumatic stress disorder (PTSD), or schizophrenia.
• Subjects with alcohol or substance abuse or dependence (except nicotine) unless in full remission for at least 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo 2 oral tablets twice a day for 24 weeks (first week titration)
Active Comparator: Varenicline Tartrate	Drug: Varenicline Tartrate; Varenicline Tartrate oral tablets 2 (0.5mg) tablets twice a day for 24 weeks (first week titration)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Carbon Monoxide (CO) Confirmed 10-Week Continuous Abstinence (CA) From Smoking	Percentage of participants who remained abstinent from Week 15 to Week 24, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the Nicotine Use Inventory (NUI) and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 15 through 24, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).	Week 15 - 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With CO Confirmed 4-Week CA From Smoking	Percentage of participants who remained abstinent from Week 21 to Week 24, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the NUI and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 21 through 24, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).	Week 21 - 24
Percentage of Participants With CO Confirmed Long Term CA From Smoking	Percentage of participants who remained abstinent from Week 21 to Week 52, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the NUI and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 21 through 52, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).	Weeks 21 - 52
Percentage of Participants With 7-Day Point Prevalence of Smoking Cessation	The 7-day point prevalence of abstinence was defined as being abstinent from smoking and using tobacco products during the last 7 days at Week 12, 24, and 52. The participant's smoking status and other nicotine use was evaluated based on the "last 7 days" questions on the NUI and confirmed by CO expiration. Responders were defined as those, who answered "no" to both questions ("Has the subject smoked any cigarettes (even a puff) in the last 7 days?"; and "Has the subject used any nicotine products and/or other tobacco.... in the last 7 days?") and whose expired CO < 10 ppm. Missing CO was imputed as negative (CO ≤ 10 ppm).	Week 12, 24, and 52
Percentage of Participants With 4-Week Point Prevalence of Smoking Cessation	The 4-week point prevalence of abstinence was defined as being abstinent from smoking and using tobacco products during the last 4 weeks of the study. The participant's smoking status and other nicotine use was evaluated based on the "last 4 weeks" questions on the NUI and confirmed by CO expiration. Responders were defined as those, who answered "no" to both questions ("Has the subject smoked any cigarettes (even a puff) in the last 4 weeks?"; and "Has the subject used any nicotine products and/or other tobacco.... in the last 4 weeks?") and whose expired CO < 10 ppm. Missing CO was imputed as negative (CO ≤ 10 ppm).	Week 52

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.
• Nakamura M, Abe M, Ohkura M, Treadow J, Yu CR, Park PW. Efficacy of Varenicline for Cigarette Reduction Before Quitting in Japanese Smokers: A Subpopulation Analysis of the Reduce to Quit Trial. Clin Ther. 2017 Apr;39(4):863-872. doi: 10.1016/j.clinthera.2017.03.007. Epub 2017 Mar 30.
• Ebbert JO, Hughes JR, West RJ, Rennard SI, Russ C, McRae TD, Treadow J, Yu CR, Dutro MP, Park PW. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015 Feb 17;313(7):687-94. doi: 10.1001/jama.2015.280.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 9, 2011

Study Record Updates

• Last Update Posted (Estimate): September 1, 2014
• Last Update Submitted That Met QC Criteria: August 29, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: smoking cessation; smoking reduction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: A3051075; REDUCE TO QUIT