Smoking Cessation Study In Healthy Adolescent Smokers

A Twelve-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study With Follow-up Evaluating The Safety And Efficacy Of Varenicline For Smoking Cessation In Healthy Adolescent Smokers

The study is designed to see if varenicline combined with age appropriate (adolescent) smoking cessation counseling will help teens quit smoking.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Varenicline 1mg BID; Drug: Varenicline 0.5mg BID; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1Z 0M1
      • Kids Clinic
    • New Market, Ontario, Canada, L3Y 5G8
      • SKDS Research Inc.
    • Newmarket, Ontario, Canada, L3Y 5G8
      • Private Practice of Robert J. Camargo
• Georgia
  • Rustavi, Georgia, 3700
    • LTD" Rustavi Psychological Health Center"
• Korea, Republic of
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Hospital
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, Korea, Republic of, 14068
      • Hallym University Sacred Heart Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 442 723
      • The Catholic University Of Korea St. Vincent Hospital
• Russian Federation
  • Moscow, Russian Federation, 119331
    • GBUZ City childrens out-patient clinic # 10 of Moscow
  • Murmansk, Russian Federation, 183036
    • GOBUZ Murmansk Regional Narcology Dispensary
  • Novosibirsk, Russian Federation, 630091
    • LLC City Neurological Center "Sibneuromed"
  • Saint-Petersburg, Russian Federation, 190068
    • LLC " Alliance Biomedical - Russian Group"
  • Saint-Petersburg, Russian Federation, 191025
    • LLC Medical Technologies
  • Saint-Petersburg, Russian Federation, 192019
    • FSBI V.M.Bekhterev National Research Medical Center for Psychiatry and Neurology of RF MoH
  • Saint-Petersburg, Russian Federation, 192148
    • LLC Medical Technologies
  • Saint-Petersburg, Russian Federation, 197022
    • First St. Petersburg State Medical University
  • Samara, Russian Federation, 443031
    • GBUZ Samara Regional Childrens Health camp Yunost
  • Leningrad Region
    • Village Novoe Devyatkino, Leningrad Region, Russian Federation, 188661
      • Leningrad Regional Dispensary of Narcology
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital
  • Taichung city, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • Alabama
    • Ozark, Alabama, United States, 36360
      • IICR, Inc. (DBA: International Institute of Clinical Research)
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Dedicated Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Psychiatric Clinic Clinical Research Trials, P.A.
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • La Habra, California, United States, 90631
      • Omega Clinical Trials, LLC
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • Oakland, California, United States, 94607
      • Pacific Research Partners, LLC
    • Oceanside, California, United States, 92054
      • North County Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers
    • Denver, Colorado, United States, 80209
      • Western Affiliated Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • New Haven, Connecticut, United States, 06511
      • Connecticut Mental Health Center
    • New Haven, Connecticut, United States, 06511
      • Yale University, SATU
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Kissimmee, Florida, United States, 34741
      • Hope Clinical Research
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic, Inc.
    • Miami, Florida, United States, 33144
      • L & L Research Choices
    • North Bay Village, Florida, United States, 33141
      • Bravo Health Care Center
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Saint Petersburg, Florida, United States, 33716
      • Comprehensive Clinical Development Inc.
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
    • Meridian, Idaho, United States, 83646
      • Barney Greenspan, Ph.D
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Midwest Behavioral Health
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research, LLC
    • Newburgh, Indiana, United States, 47630
      • Pedia Research, LLC
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/Adult Research
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research, LLC
    • Owensboro, Kentucky, United States, 42303
      • Research Integrity, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical Trials, LLC
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, P.C.
    • O'Fallon, Missouri, United States, 63368
      • Psychiatric Care & Research Center
    • Saint Louis, Missouri, United States, 63109
      • Mid-America Clinical Research, LLC
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute, LLC
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clinical Research, Inc.
    • Toledo, Ohio, United States, 43623
      • Neurology & Neuroscience Center Of Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, L.P.
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research, LLC
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78230
      • Thomas Murray DeMoor, MD
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Clinical Research Partners, LLC
  • Washington
    • Kirkland, Washington, United States, 98033
      • Eastside Therapeutic Resource
    • Richland, Washington, United States, 99352
      • Zain Research, LLC
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation for Health Research and Education

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects between the ages of 12 and 19, inclusive.
• Subjects smoking at least an average of 5 cigarettes per day, motivated to stop smoking,
• Subjects must have at least one prior failed attempt to quit smoking.

Exclusion Criteria:

• Subjects with history, current diagnosis, or treatment of major depression disorder, anxiety disorders, panic disorder, hostility or aggression disorder, perceptual/thinking disturbances, mania, psychosis, bipolar disorder, personality disorder, eating disorder or severe emotional problems (in the past year).
• Subjects with a prior suicide attempt: subjects hospitalized within the past 12 months due to suicidal ideation or suicidal behavior; subjects considered to have serious suicidal ideation or suicidal behavior in the past 12 months; active suicidal ideation or behavior identified at the screening or baseline visit.
• Evidence of alcohol and substance abuse/dependence (other than nicotine) within 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Varenicline 1mg BID; Oral Varenicline 1mg BID, or 1/2 that dose (0.5mg BID) for those subjects that weigh less than or equal to 55kg at baseline, for twelve weeks, follow-up through Week 52	Drug: Varenicline 1mg BID; Oral Varenicline 1mg BID, or 1/2 that dose (0.5mg BID) for those subjects that weigh less than or equal to 55kg at baseline, for twelve weeks, follow-up through Week 52
Experimental: Varenicline 0.5mg BID; Oral Varenicline 0.5mg BID, or 1/2 that dose (0.5 QD) for those subjects that weigh less than or equal to 55kg at baseline, for twelve weeks, follow-up through Week 52	Drug: Varenicline 0.5mg BID; Oral Varenicline 0.5mg BID, or 1/2 that dose (0.5 QD) for those subjects that weigh less than or equal to 55kg at baseline, for twelve weeks, follow-up through Week 52
Placebo Comparator: Placebo; Oral placebo for twelve weeks,follow-up through Week 52	Drug: Placebo; Oral placebo for twelve weeks,follow-up through Week 52

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
4-Week Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 12	The percentage of participants who, at each visit from Week 9 through Week 12, reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory) and at each of these visits were confirmed to have quit based on urine cotinine less than 200 nanograms/milliliter (ng/mL).	Week 9 through Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With 7-Day Point Prevalence of Smoking Abstinence at Weeks 12, 24 and 52	The percentage of participants who reported no smoking and no use of other nicotine-containing products (treatment phase) or tobacco products (non-treatment phase) on the Nicotine Use Inventory in the 7 days prior to the study visits or telephone contacts at Week 12,24 and 52.	Weeks 12, 24 and 52
Daily Number of Cigarettes Smoked at Baseline	The average number of cigarettes smoked per day in the past 7 days reported at the baseline visit.	Baseline
Change From Baseline in Daily Number of Cigarettes Smoked at Weeks 12, 24, and 52	The reduction in the number of the cigarettes smoked was calculated by subtracting the reported average number of cigarettes smoked per day in the past 7 days at Weeks 12, 24 and 52 from the average number of cigarettes smoked per day in the past 7 days reported at the baseline visit.	Baseline, Weeks 12, 24, and 52
Continuous Abstinence Rate: Percentage of Participants Who Remained Abstinent From Week 9 Through Week 24 and Week 52	The percentage of participants who, at each visit from Week 9 to 52 (inclusive), reported no smoking and no use of other nicotine-containing products (Weeks 9-12) or tobacco products (Weeks 13-52) since the last study visit/last contact (on the Nicotine Use Inventory) and at any of the study visits were confirmed to have quit based on urine cotinine less than 200 ng/mL.	Week 9 through Week 24; Week 9 through Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious AEs and SAEs.	First dose up to last dose (up-to Week 12) plus 30 days
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug Varenicline was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious AEs and SAEs.	First dose up to last dose (up-to Week 12) plus 30 days
Number of Participants With Treatment-Emergent Neuropsychiatric Adverse Event Elicited by Neuropsychiatric Adverse Event Interview (NAEI)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE: AE causing: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Solicited AEs collected by semi-structured NAEI inquiring about AEs: depression, anxiety, delusions, hallucinations, paranoia, psychosis, mania, panic, agitation, dissociative states, feeling abnormal, hostility, aggression and homicidal ideation. If a participant had a positive response to any item on the NAEI, investigator determined if it met criteria AE criteria.	First dose up to last dose (up-to Week 12) plus 30 days
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories);was an interview-based instrument to systematically assess suicidal ideation and suicidal behavior.C-SSRS assessed whether participant experienced any of the following:completed suicide;suicide attempt(response of "Yes" on "actual attempt");preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior","aborted attempt" or "interrupted attempt"),suicidal ideation ("Yes" on "wish to be dead","non-specific active suicidal thoughts","active suicidal ideation with methods without intent to act or some intent to act,without specific plan or with specific plan and intent,any self-injurious behavior with no suicidal intent ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").Here,number of participants with positive response (response of "yes") to suicidal behavior or/and Ideation,any non-suicidal self-injurious behavior were reported.	Screening, Baseline, Week 1 up to Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (last follow-up [FU])
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A) Total Scores at Specified Time-points	The HADS is a self-administered questionnaire measuring anxiety. Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) consisted of 7 items that were assessed on a scale of 0 = no anxiety to 3 = severe feeling of anxiety. Total HADS-A subscale score range from 0 = no anxiety to 21 = severe anxiety; higher scores indicated more severe anxiety.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 28, 36, 44, and 52
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores - Depression Total Score at Specified Time-Points	Hospital Anxiety and Depression Scale Depression subscale (HADS-D) consists of 7 items that were assessed on a scale of 0 = no depression to 3 = severe feeling of depression. Total HADS-D subscale score range from 0 = no depression to 21 = severe feeling of depression; higher scores indicated a greater intensity of depression.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 28, 36, 44, and 52
Number of Participants With Laboratory Abnormalities	Criteria for laboratory abnormalities: Lymphocytes Absolute (Abs), Lymphocytes percentage (%), Total Neutrophils (Abs), Neutrophils %: <0.8*LLN or >1.2*ULN; Basophils (Abs), Basophils %Eosinophils (Abs), Eosinophils %, Monocytes (Abs), Monocytes %:> 1.2*ULN; Total Bilirubin milligram per deciliter (mg/dl) >1.5*ULN; alanine aminotransferase: >3.0*ULN; Blood urea nitrogen, Creatinine: >1.3*ULN; Uric acid :> 1.2*ULN.	Baseline up to Week 12
Change From Baseline in Blood Pressure (BP) at Week 12	Measurement of BP included supine and sitting systolic BP, standing systolic BP, supine and sitting diastolic BP and standing diastolic BP. Blood pressure was taken after participants rested in a sitting position for 5 minutes. BP was recorded after participants had been supine for approximately 5 minutes, and then orthostatic blood pressure was recorded immediately when the participant stood.	Baseline, Week 12
Change From Baseline in Pulse Rate at Week 12	Measurement of pulse rate included supine, sitting and standing pulse rate. Pulse rate was taken after participants rested in a sitting position for 5 minutes. Pulse rate was recorded after participants had been supine for approximately 5 minutes and then immediately upon standing.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Fediuk DJ, Sweeney K, Sahasrabudhe V, McRae T, Byon W. Population pharmacokinetics and exposure-response analyses of varenicline in adolescent smokers. CPT Pharmacometrics Syst Pharmacol. 2021 Jul;10(7):769-781. doi: 10.1002/psp4.12645. Epub 2021 Jun 17.
• Gray KM, Rubinstein ML, Prochaska JJ, DuBrava SJ, Holstein AR, Samuels L, McRae TD. High-dose and low-dose varenicline for smoking cessation in adolescents: a randomised, placebo-controlled trial. Lancet Child Adolesc Health. 2020 Nov;4(11):837-845. doi: 10.1016/S2352-4642(20)30243-1. Epub 2020 Sep 25.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: March 9, 2011
• First Submitted That Met QC Criteria: March 9, 2011
• First Posted (Estimate): March 11, 2011

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: smoking cessation in adolescents
• 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: A3051073; CHANTIX (Other Identifier: Alias Study Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No