The Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette

Smoking Cessation Clinical Trial

Official title:

A Randomized Controlled Trial to Determine the Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05205811
• Other study ID #: BuZonE 2
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: Rose Research Center, LLC
• Contact: Derek Mercedes
• Phone: 704-350-2999
• Email: derek.mercedes[@]roseresearchcenter.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: June 30, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Has signed the ICF and is able to read and understand the information provided in the ICF.

2. Is 21 to 65 years of age (inclusive) at screening.

3. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.

4. Has an expired air CO reading of at least 10 ppm at screening.

5. Is interested in switching to an electronic cigarette.

6. Is willing and able to comply with the requirements of the study.

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

Exclusion Criteria:

1. 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).

2. 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.

3. Has plans to use an FDA-approved smoking cessation product during the study.

4. Has high blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening.

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

6. 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.

7. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.

8. Is taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.

9. Has used any of these products in the past 30 days:

1. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);

2. Experimental (investigational) drugs that are unknown to participant;

3. Chronic opiate use.

10. 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.

11. Has a plan to use an FDA-approved quit-smoking treatment in the next 30 days.

12. Is pregnant or nursing (by self-report) or has a positive pregnancy test.

13. Enrollment requirements met.

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

Drug:
• Bupropion
Extended-release bupropion dosing (150 mg each morning days 1-3, then 300 mg/daily) for the remainder of the 7 weeks.
• Zonisamide
Zonisamide (100 mg/daily) for 7 weeks.
• Placebo bupropion
Placebo bupropion for 7 weeks.
• Placebo zonisamide
Placebo zonisamide for 7 weeks.

Other:
• E-cigarette
e-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks.

Locations

Country	Name	City	State
United States	Rose Research Center	Charlotte	North Carolina
United States	Rose Research Center	Raleigh	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Rose Research Center, LLC	Foundation for a Smoke Free World INC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tolerability of study drugs as measured by frequency of drug termination or drug non-adherence	The frequency of drug termination or non-adherence prior to Week 8 will be tabulated for each condition. Adverse effects will also be tabulated for each condition, including the following adverse effects of special interest (AESIs): insomnia, agitation, dry mouth, somnolence, headache, nausea, constipation, diarrhea, dizziness or loss of appetite.	Baseline, Week 1, Week 2, Week 4, Week 8
Other	Seven-day point abstinence at 6 months post-switch	Seven-day point abstinence at 6 months post-switch will be assessed by self-report and confirmed by exhaled carbon monoxide (CO) < 5 ppm.	6 Months post Switch Day
Primary	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	After 8 weeks
Primary	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)	Baseline, Week 8, Week 12
Primary	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	Daily from Week 2 to Week 12
Secondary	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.	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Secondary	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.	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12