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

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy of extended bupropion(6 months) versus standard bupropion treatment (7 weeks) among African American daily smokers.

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.

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

Research shows that Bupropion helps people quit smoking better than nicotine patches and increases success rates in quitting smoking. It has been effective in various studies, including those involving healthcare professionals. ^{1 2 3 4 5}

Is bupropion safe for smoking cessation?

Bupropion, used for smoking cessation, has been associated with minimal side effects in trials, but there are reports of adverse reactions and a warning about potential suicidal behavior and depression. Most exposures to bupropion were unintentional, with some serious effects noted, especially in cases of overdose. ^{5 6 7 8 9}

How is the drug bupropion unique for smoking cessation?

Bupropion is unique for smoking cessation because it is one of the first non-nicotine medications used for this purpose, and it works by affecting brain chemicals related to addiction. It is often used in combination with cognitive-behavioral therapy (CBT) to improve success rates, and it has been shown to have minimal side effects compared to other treatments. ^{2 5 10 11 12}

Research Team

Lisa Sanderson Cox, PhD

Principal Investigator

University of Kanas Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

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]

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 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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation. [2019]

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

Bupropion SR vs placebo for smoking cessation in health care professionals. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

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

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. Ireland 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. [2018]

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

Using extended cognitive behavioral treatment and medication to treat dependent smokers. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. [2022]

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

Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial. [2023]