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

NCT ID: NCT05205811

Last Updated: 2026-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-14
• Study Completion Date: 2025-10-13

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo with e-cigarette

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).

Group Type: PLACEBO_COMPARATOR

Placebo bupropion

Intervention Type: DRUG

Placebo bupropion for 7 weeks.

Placebo zonisamide

Intervention Type: DRUG

Placebo zonisamide for 7 weeks.

E-cigarette

Intervention Type: OTHER

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

Combination zonisamide and bupropion with e-cigarette

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).

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

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

Zonisamide

Intervention Type: DRUG

Zonisamide (100 mg/daily) for 7 weeks.

E-cigarette

Intervention Type: OTHER

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

Bupropion with e-cigarette

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).

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

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

Placebo zonisamide

Intervention Type: DRUG

Placebo zonisamide for 7 weeks.

E-cigarette

Intervention Type: OTHER

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

Interventions

Bupropion

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

Intervention Type: DRUG

Zonisamide

Zonisamide (100 mg/daily) for 7 weeks.

Intervention Type: DRUG

Placebo bupropion

Placebo bupropion for 7 weeks.

Intervention Type: DRUG

Placebo zonisamide

Placebo zonisamide for 7 weeks.

Intervention Type: DRUG

E-cigarette

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

Intervention Type: OTHER

Other Intervention Names

Wellbutrin; Zyban; zonegran; JUUL

Eligibility Criteria

Inclusion Criteria

1. Has signed the ICF and is able to read and understand the information provided in the ICF.

2. Is 21 to 65 years of age (inclusive) at screening.

3. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.

4. Has an expired air CO reading of at least 10 ppm at screening.

5. Is interested in switching to an electronic cigarette.

6. Is willing and able to comply with the requirements of the study.

7. Owns a smartphone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria

1. 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).

2. 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.

3. Has plans to use an FDA-approved smoking cessation product during the study.

4. Has high blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening.

5. Has body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.

6. 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.

7. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.

8. Is taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.

9. Has used any of these products in the past 30 days:

1. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);

2. Experimental (investigational) drugs that are unknown to participant;

3. Chronic opiate use.

10. 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.

11. Has a plan to use an FDA-approved quit-smoking treatment in the next 30 days.

12. Is pregnant or nursing (by self-report) or has a positive pregnancy test.

13. Enrollment requirements met.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Foundation for a Smoke Free World INC

OTHER

Sponsor Role: collaborator

Rose Research Center, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Rose Research Center

Charlotte, North Carolina, United States

Rose Research Center

Raleigh, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37230961 (View on PubMed)

Other Identifiers

BuZonE 2

Identifier Type: -

Identifier Source: org_study_id