Smoking CessationPhase 3NCT05205811
The Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette
A Phase 3 study testing Bupropion, Zonisamide and E-cigarette in people with Smoking Cessation, run by Rose Research Center, LLC at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking Cessation
- What is being tested?
- Bupropion, Zonisamide and E-cigarette
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Dec 2021to 13 Oct 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Enrollment requirements met.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Rose Research Center
Charlotte, North Carolina, 28262
Rose Research Center
Raleigh, North Carolina, 27617
About this study
Official title: A Randomized Controlled Trial to Determine the Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette
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
- Being tested
- Bupropion, Zonisamide, Placebo bupropion, Placebo zonisamide, E-cigarette
- Keywords
- e-cigarette, zonisamide, bupropion, combustible cigarettes
- Medical subject headings
- Smoking Cessation, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BupropionDrug
Also called Wellbutrin, Zyban
Extended-release bupropion dosing (150 mg each morning days 1-3, then 300 mg/daily) for the remainder of the 7 weeks.
ZonisamideDrug
Also called zonegran
Zonisamide (100 mg/daily) for 7 weeks.
Placebo bupropionDrug
Placebo bupropion for 7 weeks.
Placebo zonisamideDrug
Placebo zonisamide for 7 weeks.
E-cigaretteOther
Also called JUUL
e-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: Drug: Placebo bupropion; Drug: Placebo zonisamide; Other: E-cigarette |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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
Measured: Daily from Week 2 to Week 12
Secondary outcomes (2)
Change in Smoking withdrawal symptoms
Smoking withdrawal symptoms will be collected using a questionnaire developed by Drs. Shiffman and Jarvik (1976), which assesses craving for cigarettes, negative mood, arousal, missing the habit of smoking, changes in appetite and somatic symptoms and a seven-point scale (from 1-Not at All to 7-Extremely). Higher scores indicate more withdrawal symptoms.
Measured: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Change in Rewarding and aversive effects of smoking and e-cigarette use
The mCEQ-E will be utilized to assess the degree to which participants experience the reinforcing of smoking, providing five subscale scores: smoking satisfaction (satisfying, tastes good,enjoy smoking), psychological rewards (calms down, more awake, less irritable, helps concentrate, reduces hunger), aversion (dizziness, nauseated), enjoyment of respiratory tract sensations (single-item assessment), craving reduction (single-item assessment). Participants will be asked to assess the 12 items of the questionnaire on a 7-point scale, ranging from "not at all" to "extremely". These 12 items will be asked for the "first cigarette smoked", "cigarette immediately after a meal", and "all other cigarettes." The e-cigarette version of this questionnaire (mECEQ-E) will also be used.
Measured: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2022
- Study start14 Dec 2021
- Primary completion19 Jun 2025
- Study completion13 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rose Research Center, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Foundation for a Smoke Free World INC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05205811
- Sponsor's protocol ID
- BuZonE 2
- Status last verified
- Feb 2026
- First submitted
- 27 Oct 2021
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37230961
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial to Determine the Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette
- ClinicalTrials.gov ID
- NCT05205811
- Acronym / sponsor ID
- BuZonE 2
- Conditions
- Smoking Cessation
- Keywords
- e-cigarette, zonisamide, bupropion, combustible cigarettes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Rose Research Center, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Foundation for a Smoke Free World INC
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- 19 Jun 2025 (actual)
- Study completion
- 13 Oct 2025 (actual)
- First posted
- 25 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Combination zonisamide and bupropion with e-cigarette | Experimental | Drug: Bupropion, Drug: Zonisamide, Other: E-cigaretteAfter 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). |
| Bupropion with e-cigarette | Experimental | Drug: Bupropion, Drug: Placebo zonisamide, Other: E-cigaretteAfter 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). |
| Placebo with e-cigarette | Placebo comparator | Drug: Placebo bupropion, Drug: Placebo zonisamide, Other: E-cigaretteAfter 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). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BupropionAlso: Wellbutrin, ZybanExtended-release bupropion dosing (150 mg each morning days 1-3, then 300 mg/daily) for the remainder of the 7 weeks. | Drug | Bupropion with e-cigarette, Combination zonisamide and bupropion with e-cigarette |
| ZonisamideAlso: zonegranZonisamide (100 mg/daily) for 7 weeks. | Drug | Combination zonisamide and bupropion with e-cigarette |
| Placebo bupropionPlacebo bupropion for 7 weeks. | Drug | Placebo with e-cigarette |
| Placebo zonisamidePlacebo zonisamide for 7 weeks. | Drug | Bupropion with e-cigarette, Placebo with e-cigarette |
| E-cigaretteAlso: JUULe-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks. | Other | Bupropion with e-cigarette, Combination zonisamide and bupropion with e-cigarette, Placebo with e-cigarette |
Primary outcome
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by Exhaled carbon monoxide (CO)
Time frame: After 8 weeks
Exhaled carbon monoxide (CO) < 5 ppm at the end of drug treatment
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by change in Total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
Time frame: Baseline, Week 8, Week 12
Total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by change in self-report of daily cigarette and e-cigarette use
Time frame: Daily from Week 2 to Week 12
Self-report of daily cigarette and e-cigarette use
2 secondary outcomes
Change in Smoking withdrawal symptoms
Time frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Change in Rewarding and aversive effects of smoking and e-cigarette use
Time frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Derived from this study: PubMed 37230961Hajizadeh 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bupropion, Zonisamide and E-cigarette in people with Smoking Cessation, run by Rose Research Center, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by Exhaled carbon monoxide (CO) (time frame: After 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05205811, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.