Nicotine Dependence
Conditions
Brief summary
This is a placebo-controlled smoking cessation treatment study for adolescents ages 14-21. After assessment and inclusion into the study, participants will be randomized to receive a 12-week double blind course of varenicline or placebo.
Detailed description
The objective of this protocol is to examine the efficacy and safety of varenicline for smoking cessation in adolescents. The guiding design philosophy was to model the adult smoking cessation literature (allowing for indirect comparisons of efficacy in different populations) while fine-tuning some elements specifically geared for adolescents. After assessment and inclusion into the study, participants will be randomized to receive a 12-week double blind course of varenicline or placebo. Participants will provide smoking self-report (cigarettes per day) throughout the study. Biological confirmation with carbon monoxide breathalyzer will occur at all visits, and urine cotinine measurement will occur at key time points (baseline, end of treatment and final post-treatment follow-up). Psychiatric/medical visits will occur weekly throughout active treatment to systematically monitor safety and tolerability. After the 12-week treatment course, participants will return for 3 post-treatment follow-up visits (Week 13, Week 18, and Week 26).
Interventions
DRUGVarenicline
participants \>55 kg will take varenicline/placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily thereafter. Participants ≤55 kg will take varenicline/placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily thereafter.
DRUGplacebo
participants \>55 kg will take varenicline/placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily thereafter. Participants ≤55 kg will take varenicline/placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily thereafter.
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Age 14-21 * Daily smoker for ≥6 months * Desire to quit smoking, with at least one prior failed quit attempt and willingness to participate in a treatment study * If under age 18, parent(s) or guardian(s) able to participate in informed consent and initial assessment (unless the participant provides evidence of emancipated status) * If female, agreement to use birth control (any form of hormonal contraception such as Depo-Provera, daily oral contraception, transdermal patch, or Nuva-ring; intrauterine device; sterilization; or double barrier contraception, which is a combination of any two of the following methods: condoms, spermicide, diaphragm) to avoid pregnancy
Exclusion criteria
* Lifetime history of any DSM-IV-TR mood or psychotic disorder (e.g., major depressive disorder, bipolar disorder, schizophrenia) * Lifetime history of suicidality, homicidality, or clinically significant hostility/aggression * Current substance dependence, other than nicotine * Current unstable major medical disorder * Current pregnancy or breastfeeding * Current use of medications with smoking cessation efficacy * Known hypersensitivity to varenicline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cotinine-confirmed 7-day Point Prevalence Abstinence at the End of Treatment | 7 days at end of treatment | Self-reported 7-day cigarette abstinence, confirmed by urine corinne ≤50 ng/mL at the end-of-treatment (week 12) visit |
| Number of Participants Experiencing Treatment-emergent Adverse Events | 26 weeks (12 weeks of treatment plus full post-treatment follow-up) | Clinician-collected adverse events (regardless of relatedness to medication) occurring at any point after randomization and initiation of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Visits With Abstinence During Treatment | 12 weeks (all of active treatment) | Self-reported between-visit abstinence at weekly visits during treatment (reported as percentage of total possible visits across all participants at which participants self-reported abstinence). Missing data were imputed to non-abstinence. |
| Percentage of Post-treatment Visits With Abstinence | One week abstinence at the Week 16 and Week 26 post-treatment follow-up visits | Self-reported abstinence at post-treatment follow-up visits (reported as percentage of total possible post-treatment follow-up visits at which abstinence in the prior week was self-reported). Missing data were imputed to non-abstinence. |
| Number of Participants Achieving 7+ Days Abstinence at Any Point During Treatment | 12 weeks of active treatment | Number of participants achieving 7+ days of self-reported abstinence at any point during active treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Participants \>55 kg will take varenicline 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily for 11 weeks. Participants ≤55 kg will take varenicline 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily for 11 weeks.
Varenicline: participants \>55 kg will take varenicline/placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily thereafter. Participants ≤55 kg will take varenicline/placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily thereafter. | 77 |
| Placebo Participants \>55 kg will take placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily for 11 weeks. Participants ≤55 kg will take placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily for 11 weeks.
placebo: participants \>55 kg will take varenicline/placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily thereafter. Participants ≤55 kg will take varenicline/placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily thereafter. | 80 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 24 | 14 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 24 |
Baseline characteristics
| Characteristic | Varenicline | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 19.1 years STANDARD_DEVIATION 1.5 | 19.1 years STANDARD_DEVIATION 1.5 | 19.1 years STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 153 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 22 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 11 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 120 Participants | 66 Participants |
| Region of Enrollment United States | 77 participants | 157 participants | 80 participants |
| Sex: Female, Male Female | 28 Participants | 63 Participants | 35 Participants |
| Sex: Female, Male Male | 49 Participants | 94 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 80 |
| other Total, other adverse events | 55 / 77 | 60 / 80 |
| serious Total, serious adverse events | 0 / 77 | 0 / 80 |
Outcome results
Primary
Number of Participants Experiencing Treatment-emergent Adverse Events
Clinician-collected adverse events (regardless of relatedness to medication) occurring at any point after randomization and initiation of treatment.
Time frame: 26 weeks (12 weeks of treatment plus full post-treatment follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline | Number of Participants Experiencing Treatment-emergent Adverse Events | 55 Participants |
| Placebo | Number of Participants Experiencing Treatment-emergent Adverse Events | 60 Participants |
Primary
Number of Participants With Cotinine-confirmed 7-day Point Prevalence Abstinence at the End of Treatment
Self-reported 7-day cigarette abstinence, confirmed by urine corinne ≤50 ng/mL at the end-of-treatment (week 12) visit
Time frame: 7 days at end of treatment
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline | Number of Participants With Cotinine-confirmed 7-day Point Prevalence Abstinence at the End of Treatment | 4 Participants |
| Placebo | Number of Participants With Cotinine-confirmed 7-day Point Prevalence Abstinence at the End of Treatment | 4 Participants |
Secondary
Number of Participants Achieving 7+ Days Abstinence at Any Point During Treatment
Number of participants achieving 7+ days of self-reported abstinence at any point during active treatment
Time frame: 12 weeks of active treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline | Number of Participants Achieving 7+ Days Abstinence at Any Point During Treatment | 31 Participants |
| Placebo | Number of Participants Achieving 7+ Days Abstinence at Any Point During Treatment | 24 Participants |
Secondary
Percentage of Post-treatment Visits With Abstinence
Self-reported abstinence at post-treatment follow-up visits (reported as percentage of total possible post-treatment follow-up visits at which abstinence in the prior week was self-reported). Missing data were imputed to non-abstinence.
Time frame: One week abstinence at the Week 16 and Week 26 post-treatment follow-up visits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Percentage of Post-treatment Visits With Abstinence | 20.8 percentage of visits with abstinence |
| Placebo | Percentage of Post-treatment Visits With Abstinence | 10.6 percentage of visits with abstinence |
Secondary
Percentage of Visits With Abstinence During Treatment
Self-reported between-visit abstinence at weekly visits during treatment (reported as percentage of total possible visits across all participants at which participants self-reported abstinence). Missing data were imputed to non-abstinence.
Time frame: 12 weeks (all of active treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Percentage of Visits With Abstinence During Treatment | 14.2 percentage of visits with abstinence |
| Placebo | Percentage of Visits With Abstinence During Treatment | 7.3 percentage of visits with abstinence |