Zonisamide + Bupropion for Smoking Cessation

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

180 Participants Needed

Trial Summary

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.

What data supports the idea that Zonisamide + Bupropion for Smoking Cessation is an effective drug?

The available research shows that bupropion, one of the components of the treatment, is effective for smoking cessation. It has been shown to reduce cravings and withdrawal symptoms, making it easier for people to quit smoking. Studies have demonstrated that bupropion is more effective than nicotine replacement therapy alone and is particularly helpful for people with conditions like depression or chronic obstructive pulmonary disease. However, there is no specific data provided on the combination of Zonisamide and Bupropion for smoking cessation. ^{1 2 3 4 5}

What data supports the effectiveness of the drug bupropion for smoking cessation?

Research shows that bupropion helps people quit smoking by reducing cravings and withdrawal symptoms. It has been effective in various groups, including those with depression and chronic health issues, and is generally safe with rare serious side effects. ^{1 2 3 4 5}

What safety data is available for the use of Zonisamide and Bupropion in smoking cessation?

Bupropion, used for smoking cessation, has been evaluated for safety in various studies. Reports have linked it to adverse reactions, including seizures, especially when combined with other medications like antidepressants or in patients with seizure disorders. However, when used according to guidelines, it is considered safe and effective. Concerns about psychiatric adverse events, such as suicidal behavior and depression, have been noted, but these risks may be related to smoking cessation itself rather than the drug. A review of bupropion exposures showed that most cases were unintentional, with some serious effects in intentional overdoses. Overall, bupropion has been associated with minimal side effects in smoking cessation trials. ^{4 6 7 8 9}

Is the combination of Zonisamide and Bupropion safe for smoking cessation?

Bupropion, used for smoking cessation, is generally considered safe when used according to guidelines, though it carries warnings about potential psychiatric effects like depression and suicidal behavior. It has been associated with minimal side effects in trials, but there are reports of adverse reactions, especially when combined with other medications. No specific safety data for the combination with Zonisamide is provided. ^{4 6 7 8 9}

Is the drug Zonisamide + Bupropion a promising option for helping people quit smoking?

Yes, Bupropion is a promising drug for helping people quit smoking. It reduces cravings and withdrawal symptoms, making it easier for people to stop smoking. It has been shown to be effective in various studies and is especially helpful for people who have other health issues like depression or heart problems. ^{2 9 10 11 12}

How does the drug Zonisamide + Bupropion differ from other smoking cessation drugs?

The combination of Zonisamide and Bupropion for smoking cessation is unique because it combines Bupropion, a non-nicotine drug that reduces cravings by affecting brain chemicals, with Zonisamide, which is not typically used for smoking cessation. This combination may offer a novel approach by potentially enhancing the effects of Bupropion, although Zonisamide's specific role in smoking cessation is not well-established. ^{2 9 10 11 12}

What is the purpose of this trial?

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).

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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, 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]

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]

References

1. United States 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. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Review of bupropion for smoking cessation. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Randomized trial of nicotine replacement therapy (NRT), bupropion and NRT plus bupropion for smoking cessation: effectiveness in clinical practice. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Bupropion exposures: clinical manifestations and medical outcome. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

[Uneasiness about the safety of bupropion as an aid to smoking cessation unjustified ]. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Use of varenicline versus bupropion and risk of psychiatric adverse events. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Suicidal behavior and depression in smoking cessation treatments. [2022]

9. Germany 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. [2022]

11. France pubmed.ncbi.nlm.nih.gov

[Acute psychotic disorders related to bupropion: review of the literature]. [2013]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Suitability of bupropion SR for nicotine-dependent smokers: problems in a practice setting. [2017]