The Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette

NCT05205811 | Completed Phase 3 FDA Drug

• 1 other identifier: BuZonE 2
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

This three-group randomized double-blind placebo-controlled trial (N=180) will evaluate the impact of combination zonisamide and bupropion on the process of switching from combustible cigarettes (CCs) to an e-cigarette. There will be a data collection period of at least five days to obtain baseline information on the use of combustible cigarettes. All participants enrolled in the study will receive a JUUL e-cigarette at Visit 2 for ad libitum use. After the first week of e-cigarette use (at Visit 3), participants will be given bupropion (150 mg each morning for days 1-3, then 300 mg daily) with either zonisamide (100 mg daily) or placebo (group 1 and group 2 respectively), or placebo for both medications (group 3) in addition to continued use of the e-cigarette. At each visit, participants will receive enough study drugs (or placebos) and e-cigarettes to last until their next study visit. The combination of zonisamide and bupropion use will continue until Visit 6 (7 weeks of treatment), and e-cigarette use will continue until the end of treatment (Visit 7).

Conditions

Smoking Cessation

Keywords

e-cigarette; zonisamide; bupropion; combustible cigarettes

Outcome Measures

Primary Outcomes (3)

• Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by Exhaled carbon monoxide (CO)

  Exhaled carbon monoxide (CO) \< 5 ppm at the end of drug treatment

  After 8 weeks

• Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by change in Total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)

  Total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)

  Baseline, Week 8, Week 12

• Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by change in self-report of daily cigarette and e-cigarette use

  Self-report of daily cigarette and e-cigarette use

  Daily from Week 2 to Week 12

Secondary Outcomes (2)

• Change in Smoking withdrawal symptoms

  Baseline, Week 1, Week 2, Week 4, Week 8, Week 12

• Change in Rewarding and aversive effects of smoking and e-cigarette use

  Baseline, Week 1, Week 2, Week 4, Week 8, Week 12

Other Outcomes (2)

• Tolerability of study drugs as measured by frequency of drug termination or drug non-adherence

  Baseline, Week 1, Week 2, Week 4, Week 8

• Seven-day point abstinence at 6 months post-switch

  6 Months post Switch Day

Study Arms (3)

Combination zonisamide and bupropion with e-cigarette

EXPERIMENTAL

After the first week of e-cigarette use (JUUL), participants will be given bupropion (150 mg each morning for days 1-3, then 300 mg daily) with zonisamide (100 mg daily). The combination of zonisamide and bupropion use will continue for 7 weeks of treatment, and e-cigarette use will continue until the end of the study (an additional 4 weeks).

Drug: Bupropion; Drug: Zonisamide; Other: E-cigarette

Bupropion with e-cigarette

EXPERIMENTAL

After the first week of e-cigarette use (JUUL), participants will be given bupropion (150 mg each morning for days 1-3, then 300 mg daily) with placebo zonisamide. The combination of placebo and bupropion use will continue for 7 weeks of treatment, and e-cigarette use will continue until the end of the study (an additional 4 weeks).

Drug: Bupropion; Drug: Placebo zonisamide; Other: E-cigarette

Placebo with e-cigarette

PLACEBO COMPARATOR

After the first week of e-cigarette use (JUUL), participants will be given placebo bupropion with placebo zonisamide. The combination of these placebos will continue for 7 weeks of treatment, and e-cigarette use will continue until the end of the study (an additional 4 weeks).

Drug: Placebo bupropion; Drug: Placebo zonisamide; Other: E-cigarette

Interventions

Bupropion DRUG

Extended-release bupropion dosing (150 mg each morning days 1-3, then 300 mg/daily) for the remainder of the 7 weeks.

Also known as: Wellbutrin, Zyban

Bupropion with e-cigarette; Combination zonisamide and bupropion with e-cigarette

Zonisamide DRUG

Zonisamide (100 mg/daily) for 7 weeks.

Also known as: zonegran

Combination zonisamide and bupropion with e-cigarette

Placebo bupropion DRUG

Placebo bupropion for 7 weeks.

Placebo with e-cigarette

Placebo zonisamide DRUG

Placebo zonisamide for 7 weeks.

Bupropion with e-cigarette; Placebo with e-cigarette

E-cigarette OTHER

e-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks.

Also known as: JUUL

Bupropion with e-cigarette; Combination zonisamide and bupropion with e-cigarette; Placebo with e-cigarette

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has signed the ICF and is able to read and understand the information provided in the ICF.
• Is 21 to 65 years of age (inclusive) at screening.
• Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.
• Has an expired air CO reading of at least 10 ppm at screening.
• Is interested in switching to an electronic cigarette.
• Is willing and able to comply with the requirements of the study.
• Owns a smartphone with text message and data capabilities compatible with necessary surveys.

You may not qualify if:

• Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history).
• Has a PHQ-9 score greater than 9, or a score greater than 0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") at screening.
• Has plans to use an FDA-approved smoking cessation product during the study.
• Has high blood pressure (systolic \> 150 mmHg or diastolic \>95 mmHg) at screening.
• Has body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
• Has coronary heart disease, structural cardiac disease (including, but not limited to valvular heart disease or cardiac murmurs), cardiac dysrhythmias, syncope, cardiac chest pain, or history of heart attack or heart failure.
• Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
• Is taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.
• Has used any of these products in the past 30 days:
• Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);
• Experimental (investigational) drugs that are unknown to participant;
• Chronic opiate use.
• Has used smokeless tobacco (chewing tobacco, snuff), cigars (except for "Black \& Mild" cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of screening.
• Has a plan to use an FDA-approved quit-smoking treatment in the next 30 days.
• Is pregnant or nursing (by self-report) or has a positive pregnancy test.

Sponsors & Collaborators

• Rose Research Center, LLC: lead
• Foundation for a Smoke Free World INC: collaborator

Study Sites (2)

Rose Research Center

Charlotte, North Carolina, 28262, United States

Location

Rose Research Center

Raleigh, North Carolina, 27617, United States

Location

Related Publications (1)

• Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 10.1002/14651858.CD000031.pub6.

  PMID: 37230961 DERIVED

MeSH Terms

Conditions

Smoking Cessation; Vaping

Interventions

Bupropion; Zonisamide; Electronic Nicotine Delivery Systems

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Smoking

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: January 25, 2022
• Study Start: December 14, 2021
• Primary Completion: June 19, 2025
• Study Completion: October 13, 2025
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)