Extended Bupropion Treatment for Smoking Cessation

((KISV) Trial)

Overseen By Tricia Snow, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Kansas Medical Center

Must not be taking: Psychoactive, Opiates, Cocaine, Stimulants

Disqualifiers: Substance abuse, Seizures, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 7 weeks for standard treatment, 24 weeks for extended treatment

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a longer bupropion treatment in helping African American daily smokers quit compared to the usual treatment duration. Participants will receive either the standard 7-week bupropion treatment or an extended 24-week treatment, both with smoking cessation counseling. The trial aims to determine if a longer bupropion regimen enhances smoking cessation success. Individuals who have smoked daily for over a year and wish to quit may be suitable for this study. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to the potential approval of a more effective smoking cessation treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, especially psychoactive medications and specific drugs metabolized by the liver enzyme CYP2D6, like metoprolol and tamoxifen. You also need to avoid using stop smoking medications in the 30 days before joining the study.

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

Research has shown that bupropion is generally safe for helping people quit smoking. Studies have found it effective and well-tolerated for this purpose. To minimize the risk of seizures, it is important not to exceed 300 mg per day. The FDA reviewed large studies and concluded that a strong warning about mental health risks is no longer necessary, indicating confidence in bupropion's safety. While nicotine replacement therapy (NRT) is more common, bupropion remains a safe and cost-effective option. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for smoking cessation?

Most treatments for smoking cessation involve nicotine replacement therapy, varenicline, or short-term use of medications like bupropion. However, this study is exploring an extended use of bupropion SR that spans 24 weeks instead of the standard 7 weeks. Researchers are excited because this longer treatment duration with bupropion may enhance the ability to quit smoking by providing sustained support, potentially leading to higher long-term success rates. Additionally, both treatment groups receive comprehensive counseling, which is consistent with clinical guidelines and could further boost the effectiveness of the medication in helping individuals quit smoking.

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

Research shows that bupropion can help people quit smoking. In this trial, participants will join one of two treatment arms. The standard treatment arm will receive 7 weeks of bupropion SR, while the extended treatment arm will receive 24 weeks of bupropion SR. One study found that a higher dose of bupropion led to more people not smoking after three months. Another study showed that combining bupropion with nicotine patches or gum increased quit rates by 20% after one year. However, some studies found that using bupropion for longer than usual did not significantly improve long-term success. Overall, bupropion is considered a safe and effective option for adults who want to stop smoking. ^{4 5 6 7 8}

Who Is on the Research Team?

Lisa Sanderson Cox, PhD

Principal Investigator

University of Kanas Medical Center

Are You a Good Fit for This Trial?

This trial is for African American adults who smoke daily, want to quit, and are willing to commit to a 6-month treatment plan. Participants must not be using any stop smoking medications recently, be pregnant or breastfeeding, have had a recent heart attack, or take certain drugs metabolized by the liver enzyme CYP2D6.

Inclusion Criteria

African American

Smoked on >25 days in the past month

I want to quit smoking.

Exclusion Criteria

Other smoker in household enrolled in the study

Reported use of opiates, cocaine, or stimulants

Breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bupropion treatment with culturally-relevant smoking cessation counseling

7 weeks for standard treatment, 24 weeks for extended treatment

8 counseling sessions

Follow-up

Participants are monitored for smoking abstinence and medication adherence

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion

Trial Overview

The study compares two durations of bupropion treatment for quitting smoking: an extended course of 6 months versus the standard duration of 7 weeks. It aims to determine which is more effective in helping African American smokers achieve abstinence.

How Is the Trial Designed?

Group I: Standard Treatment Active Control 1 Intervention

250 participants will be randomly assigned to the standard treatment arm and receive 7 weeks of bupropion SR following standard dosing guidelines(150 mg once daily for 3 days, then 150mg twice daily for 7 weeks). Participants in this arm will also receive 8 smoking cessation counseling sessions consistent with the Clinical Practice Guidelines.

Group II: Extended Treatment Active Control 1 Intervention

250 participants will be randomly assigned to the extended treatment arm and receive 24 weeks of bupropion SR following standard dosing guidelines(150 mg once daily for 3 days, then 150mg twice daily for 24 weeks). Participants in this arm will also receive 8 smoking cessation counseling sessions consistent with the Clinical Practice Guidelines.

Bupropion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in Canada as Zyban for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

In a study involving 707 smokers, bupropion sustained release (SR) combined with counseling significantly increased smoking cessation rates, with a continuous abstinence rate of 46% compared to 23% for placebo during weeks 4 to 7.

At the 12-month mark, the continuous abstinence rate was 21% for the bupropion SR group versus 11% for placebo, indicating long-term effectiveness, although some participants experienced higher rates of side effects like insomnia and dry mouth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation. Tønnesen, P., Tonstad, S., Hjalmarson, A., et al.[2019]

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 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]

In a study involving 687 physicians and nurses, bupropion SR was found to be more effective than placebo for smoking cessation, with a 50% success rate compared to 40% for the placebo group after 4 weeks.

Although bupropion SR was effective during treatment, the high placebo response in this population meant that the differences in success rates did not persist after treatment ended, highlighting the need for additional relapse prevention strategies for long-term abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion SR vs placebo for smoking cessation in health care professionals. Zellweger, JP., Boelcskei, PL., Carrozzi, L., et al.[2019]

A study involving 406 smokers evaluated the effectiveness of extended treatment with sustained-release bupropion and cognitive-behavioral therapy (CBT) over 40 weeks, showing that all extended treatments were more effective than standard treatment.

CBT, when combined with treatment, significantly improved long-term smoking abstinence rates at weeks 64 and 104, suggesting that brief provider contact and CBT can enhance long-term success in quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using extended cognitive behavioral treatment and medication to treat dependent smokers. Hall, SM., Humfleet, GL., Muñoz, RF., et al.[2021]

In a study involving 1524 adult smokers, bupropion SR (300 mg) combined with behavioral counseling showed a significantly higher rate of nonsmoking at 3 months compared to the lower dose (150 mg), indicating that higher doses may enhance smoking cessation efforts.

At 12 months, participants receiving moderate intensity counseling had a significantly higher rate of nonsmoking, suggesting that the intensity of behavioral support plays a crucial role in the effectiveness of smoking cessation interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial. Swan, GE., McAfee, T., Curry, SJ., et al.[2023]

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]

Following the FDA's black box warning in 2009, the use of varenicline among smokers significantly declined from 22.1% in 2007 to 9.23% in 2014, indicating concerns over neuropsychiatric side effects influenced prescribing practices.

In contrast, the use of bupropion remained stable before and after the warning, suggesting that the BBW had a more pronounced impact on varenicline than on bupropion usage among smokers advised to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in utilization of smoking cessation agents before and after the passage of FDA boxed warning in the United States. Shah, D., Shah, A., Tan, X., et al.[2018]

In a 52-week study involving 746 participants, varenicline was found to be significantly more effective than transdermal nicotine replacement therapy (NRT) for smoking cessation, with a continuous abstinence rate of 55.9% compared to 43.2% for NRT during the last 4 weeks of treatment.

Varenicline also led to significantly lower levels of craving, withdrawal symptoms, and smoking satisfaction compared to NRT, although it had a higher incidence of nausea as a side effect (37.2% for varenicline vs. 9.7% for NRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Aubin, HJ., Bobak, A., Britton, JR., et al.[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 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]

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]

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pmc.ncbi.nlm.nih.gov

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

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jamanetwork.com

jamanetwork.com/journals/jamainternalmedicine/fullarticle/217331

Bupropion for Smoking Cessation: A Randomized Trial

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pmc.ncbi.nlm.nih.gov/articles/PMC10858725/

A Review of Smoking Cessation Interventions - PubMed Central

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cdc.gov

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How to Use Bupropion SR | Quit Smoking

All have been shown to be safe and effective for adults who smoke cigarettes. These quit-smoking medicines include nicotine replacement medicines (the nicotine ...

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jamanetwork.com

jamanetwork.com/journals/jamainternalmedicine/fullarticle/216228

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Results At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate ...

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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.

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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 ...

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smoking medicines Chantix (varenicline) and Zyban ( ...

As a result of our review of the large clinical trial, we are removing the Boxed Warning,. FDA's most prominent warning, for serious mental ...