Zonisamide + Bupropion for Smoking Cessation

Not currently recruiting at 1 trial location

Overseen By Jed E Rose, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rose Research Center, LLC

Must not be taking: Antidepressants, Antipsychotics, Benzodiazepines, others

Disqualifiers: Coronary heart disease, High blood pressure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining zonisamide and bupropion (an antidepressant) can help people switch from regular cigarettes to e-cigarettes more effectively. Participants will be divided into three groups: one receiving both drugs, another receiving bupropion and a placebo, and the last receiving only placebos. The trial seeks adults who smoke at least 10 cigarettes a day and are interested in trying e-cigarettes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications to join the trial?

Yes, you must stop taking antidepressants, psychoactive medications, or medications that prolong QTc to participate in the trial.

Will I have to stop taking my current medications?

Yes, you will need to stop taking antidepressants, psychoactive medications, or medications that prolong QTc to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bupropion is a well-known medication used to help people quit smoking. The FDA has approved it for this purpose, and it is generally considered safe at the recommended dose of 300 mg per day. This dosage helps lower the risk of seizures, which can occur with higher doses.

Studies have indicated that zonisamide might help reduce nicotine withdrawal symptoms. However, reports of side effects like seizures, especially when taken with other medications, suggest its safety may be more complex compared to bupropion.

Caution is advised when using zonisamide and bupropion together. Limited information exists on their combined use. However, testing this combination in a late-stage trial suggests some confidence in its safety at this point.

In summary, bupropion generally has a good safety record, supported by FDA approval. Zonisamide's safety is less clear, especially when combined with other drugs, so monitoring for side effects is important for those considering participation in trials involving this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of zonisamide and bupropion for smoking cessation because it offers a novel approach compared to the standard treatments like nicotine replacement therapies, varenicline, and bupropion alone. Zonisamide, typically used for epilepsy and weight loss, introduces a new mechanism of action by potentially influencing neurotransmitter pathways not targeted by existing smoking cessation aids. When combined with bupropion, which is already known to help reduce nicotine cravings and withdrawal symptoms, this duo could enhance the effectiveness of quitting smoking. Additionally, the use of e-cigarettes in this approach may help manage nicotine addiction more flexibly, potentially increasing success rates for individuals trying to quit smoking.

What evidence suggests that this trial's treatments could be effective for smoking cessation?

Studies have shown that bupropion can help people quit smoking. In earlier trials, participants taking bupropion had higher success rates compared to those taking a placebo. Specifically, 27% of participants quit smoking with bupropion, while only 11% quit with a placebo after 26 weeks. Research also shows that combining bupropion with nicotine replacement therapy, such as patches, can further increase quit rates. In this trial, some participants will receive bupropion with an e-cigarette, while others will receive a combination of zonisamide and bupropion with an e-cigarette. Zonisamide has been found to reduce withdrawal symptoms and cravings, but it might not help people quit smoking on its own. This trial studies the combination of zonisamide and bupropion to see if it can improve the chances of quitting by better managing cravings and withdrawal symptoms. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for smokers aged 21-65 who smoke at least 10 cigarettes daily for the past year, want to switch to e-cigarettes, and can use a smartphone with text and data. Excluded are those with certain health issues like high blood pressure or heart disease, depression risks (PHQ-9 score >9), using other smoking cessation methods or psychoactive drugs, pregnant/nursing women, or anyone deemed unfit by medical staff.

Inclusion Criteria

You want to start using an electronic cigarette.

I have been smoking at least 10 cigarettes daily for the past year.

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

Exclusion Criteria

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.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Data Collection

Data collection period of at least five days to obtain baseline information on the use of combustible cigarettes

1 week

1 visit (in-person)

Treatment

Participants receive JUUL e-cigarette and are given bupropion with either zonisamide or placebo for 7 weeks

7 weeks

Weekly visits (in-person)

Extended E-cigarette Use

Continued use of e-cigarette for an additional 4 weeks after drug treatment

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion
• Zonisamide

Trial Overview The study tests if combining Zonisamide and Bupropion helps people switch from regular cigarettes to e-cigarettes. Participants will first use an e-cigarette alone then take either both drugs, one drug plus placebo, or double placebo alongside continued e-cigarette use over seven weeks in this three-group randomized double-blind trial.

How Is the Trial Designed?

Group I: Combination zonisamide and bupropion with e-cigarette Experimental Treatment 3 Interventions

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 II: Bupropion with e-cigarette Experimental Treatment 3 Interventions

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 III: Placebo with e-cigarette Placebo Group 3 Interventions

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).

Who Is Running the Clinical Trial?

Rose Research Center, LLC

Lead Sponsor

Trials

17

Recruited

1,600+

Foundation for a Smoke-Free World

Collaborator

Trials

10

Recruited

1,100+

Foundation for a Smoke Free World INC

Collaborator

Trials

15

Recruited

2,100+

Published Research Related to This Trial

Varenicline is the most effective first-line pharmacotherapy for smoking cessation, showing a significant effect compared to placebo with an odds ratio of 2.27, followed by bupropion (1.69) and nicotine replacement therapy (1.60).

Despite some safety concerns, regulatory agencies deem bupropion and varenicline to have a favorable benefit/risk profile, but healthcare providers should monitor patients for potential neuropsychiatric symptoms, especially in those with psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. Aubin, HJ., Luquiens, A., Berlin, I.[2022]

Bupropion hydrochloride (Zyban) is an effective non-nicotine medication for smoking cessation, showing positive outcomes across various populations, including those with depression and chronic diseases, based on a review of over 4,000 subjects.

While bupropion is generally safe with rare serious side effects, the main concern is a low risk of seizures (about 0.1%), making it unsuitable for individuals with a history of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of bupropion for smoking cessation. Richmond, R., Zwar, N.[2013]

A post-marketing study involving 11,735 patients found that bupropion (Zyban) has a generally safe profile for smoking cessation, with minimal side effects reported, including insomnia, nausea, and dizziness as the most common adverse reactions.

The study indicated no significant increase in all-cause mortality among bupropion users compared to a control group, suggesting that bupropion is a safe option for smoking cessation in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of bupropion (Zyban) for smoking cessation from experience gained in general practice use in England in 2000. Boshier, A., Wilton, LV., Shakir, SA.[2023]

In a study involving 78 veterans participating in a smoking cessation program, only 22% were deemed appropriate candidates for bupropion SR (Zyban) treatment, indicating limited applicability in this population.

The findings suggest that while bupropion SR is effective for smoking cessation, its use may be restricted by conservative prescribing guidelines, raising concerns about its broader applicability without complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suitability of bupropion SR for nicotine-dependent smokers: problems in a practice setting. Kohlenberg, BS., Antonuccio, DO., Hayes, SC., et al.[2017]

Bupropion, an atypical antidepressant used for smoking cessation, can induce psychotic episodes in some patients, typically occurring after about 10 days of treatment at a dose of 300 mg/day, with 85% of cases reporting hallucinations.

Most patients experiencing bupropion-induced psychosis had no prior psychiatric history, suggesting that the drug may cause dopaminergic hyper-reactivity, and discontinuation usually leads to remission within 10 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute psychotic disorders related to bupropion: review of the literature]. Javelot, T., Javelot, H., Baratta, A., et al.[2013]

Bupropion, an anti-smoking drug, is considered effective and safe when used according to guidelines, but reports of 41 deaths linked to its use highlight the importance of adhering to safety protocols, especially in patients at risk for seizures.

The majority of adverse reactions involved patients combining bupropion with other medications that increase seizure risk, indicating that proper prescribing practices are crucial for minimizing risks and ensuring the drug's efficacy in smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Uneasiness about the safety of bupropion as an aid to smoking cessation unjustified ]. Wagena, EJ., de Graaf, L., Chavannes, NH., et al.[2017]

A study in Denmark involving nearly 60,000 varenicline users and about 18,000 bupropion users found that varenicline was associated with a lower risk of psychiatric adverse events compared to bupropion, with a hazard ratio of 0.69 in unmatched analyses.

In matched analyses, varenicline did not show a significant increase in psychiatric adverse events compared to bupropion, indicating that varenicline is a safe option for smoking cessation without a higher risk of psychiatric issues, even among those with a history of psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of varenicline versus bupropion and risk of psychiatric adverse events. Pasternak, B., Svanström, H., Hviid, A.[2022]

Varenicline is associated with a significantly higher risk of suicidal and self-injurious behavior, with 90% of reported cases linked to this medication, compared to only 7% for bupropion and 3% for nicotine replacement products.

Due to the substantial safety concerns regarding varenicline, it is deemed unsuitable for first-line treatment in smoking cessation, especially when considering its adverse effects compared to bupropion and nicotine replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicidal behavior and depression in smoking cessation treatments. Moore, TJ., Furberg, CD., Glenmullen, J., et al.[2022]

A review of 7,348 bupropion-only exposures revealed that while most unintentional exposures resulted in minimal toxicity, 15% of intentional overdoses led to seizures, highlighting the risks associated with misuse.

The data indicated that Wellbutrin SR was the most commonly involved product, and serious clinical effects were more prevalent in intentional overdoses, particularly among teenagers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion exposures: clinical manifestations and medical outcome. Belson, MG., Kelley, TR.[2019]

In a 10-week study involving 58 smokers with schizophrenia, the combination of sustained-release bupropion and a transdermal nicotine patch significantly increased the likelihood of achieving continuous smoking abstinence compared to a placebo plus nicotine patch, with 27.6% of participants in the treatment group abstaining versus only 3.4% in the placebo group.

The combination therapy was well-tolerated and did not significantly affect the positive or negative symptoms of schizophrenia, indicating it may be a safe option for smoking cessation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. George, TP., Vessicchio, JC., Sacco, KA., et al.[2022]

In a study of 868 smokers participating in a cognitive-behavioral program, the combination of nortriptyline and nicotine replacement therapy (NRT) was found to significantly increase smoking abstinence rates, with 36.5% abstinent at 6 months and 33.6% at 1 year.

Factors such as male gender, older age, and a longer time since the last cigarette were associated with lower abstinence rates, while neuropsychiatric comorbidities and smoking patterns in the morning were linked to treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-life study of the effectiveness of different pharmacological approaches to the treatment of smoking cessation: re-discussing the predictors of success. Prado, GF., Lombardi, EM., Bussacos, MA., et al.[2022]

In a study involving 1071 smokers, bupropion and nicotine replacement therapy (NRT) showed similar effectiveness for smoking cessation, with abstinence rates of 27.9% for bupropion and 24.2% for NRT, indicating no significant difference between the two treatments.

Bupropion may be particularly beneficial for smokers with a history of depression, as those individuals had a higher abstinence rate (29.8%) compared to those using NRT (18.5%), suggesting that treatment choice may be tailored based on mental health history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of nicotine replacement therapy (NRT), bupropion and NRT plus bupropion for smoking cessation: effectiveness in clinical practice. Stapleton, J., West, R., Hajek, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2528204/

The use of bupropion SR in cigarette smoking cessation In patients with established CVD, bupropion has similar success rates compared with healthy smokers (27% bupropion vs 11% placebo at 26 weeks, 22% vs 9% at 52 ...

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/217331

Bupropion for Smoking Cessation: A Randomized Trial One of these clinical studies reported an absolute 20% increase in 1-year quit rates among participants receiving combined bupropion plus NRT compared with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4282128/

Randomized trial of nicotine replacement therapy (NRT ... Bupropion was introduced for smoking cessation following a pivotal trial showing that it gave improved efficacy over the nicotine patch and also suggesting ...

4. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000031.pub5/full

Antidepressants for smoking cessation - Howes, S - 2020 Using the antidepressant, bupropion, makes it 52% to 77% more likely that a person will successfully stop smoking, which is equal to five to ...

5. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/216228

Effectiveness of Bupropion Sustained Release for Smoking ... Conclusions In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/020711s052lbl.pdf

Zyban - accessdata.fda.gov The risk of seizure can be reduced if the dose of ZYBAN for smoking cessation does not exceed. 300 mg per day, given as 150 mg twice daily, and titration ...

7. cdc.gov cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-bupropion-sr.html

How to Use Bupropion SR | Quit Smoking There are seven medicines approved by the Food and Drug Administration (FDA) to help you quit. They work in different ways. All have been shown to be safe ...

8. my.clevelandclinic.org my.clevelandclinic.org/health/drugs/20035-bupropion-sustained-release-tablets-smoking-cessation

Zyban (Bupropion): Uses & Side Effects BUPROPION (byoo PROE pee on) helps you quit smoking. It reduces cravings for nicotine, the addictive substance found in tobacco. It may also help reduce ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470212/

Bupropion - StatPearls - NCBI Bookshelf - NIH Bupropion is generally avoided due to limited safety data. ... Tolerability and safety of sustained-release bupropion in the management of smoking cessation.

10. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/z/zybantab.pdf

ZYBAN bupropion hydrochloride 150 mg modified release ... Limited clinical trial data suggest that higher smoking cessation rates may be achieved by the combination use of ZYBAN together with Nicotine Transdermal.