Smoking Cessation
Conditions
Keywords
Smoking Cessation, Quit Smoking, Ganaxolone, Nicotine Patch
Brief summary
The purpose of this research study is to evaluate whether the investigational drug ganaxolone can help smokers quit smoking. Ganaxolone is a drug that has been investigated (in other research studies) for the treatment of seizures and migraines. This drug is considered investigational in the US.
Detailed description
The purpose of this proof-of-concept study is to evaluate whether expired air carbon monoxide (CO) will be reduced and smoking cessation success rates enhanced for smokers who receive the neurosteroid analog ganaxolone. The trial will be seeking preliminary indications of efficacy and tolerability in the smoking population and allow us to estimate effect sizes for future controlled trials.
Interventions
DRUGGanaxolone
Pre-Quit Period: Beginning at Session P1, subjects will receive ganaxolone at a dose of 400mg total daily (200mg bid) for the first three days, 800mg total daily (400mg bid) for the next three days and 1200mg total daily (600mg bid) for the remainder of the first four weeks. Post-Quit Period: Following the quit-day, subjects will receive ganaxolone at a dose of (1200mg total daily) for the next week. Down-titration of ganaxolone will begin at post-quit week two. Subjects will receive ganaxolone at a dose of 800mg total daily (400mg bid) to take for three days and 400mg total daily (200mg bid) to take for three.
DRUGNicotine Patch
Pre-Quit Period: Beginning at Session P2, subjects will receive active 21mg/24h nicotine patches to apply daily for the next two weeks. Post-Quit Period: Following the quit-day, subjects will continue to apply active nicotine patches daily for the remainder of the study (21mg/24h for four weeks, 14mg/24h for one week, and 7mg/24h for one week).
Sponsors
National Institute on Drug Abuse (NIDA)
Jed E. Rose
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have no known serious medical conditions; * Are 18-65 years old; * Smoke an average of at least 10 cigarettes per day; * Have smoked at least one cumulative year; * Have an expired air CO reading of at least 10ppm; * Able to read and understand English; * Express a desire to quit smoking in the next thirty days. Potential subjects must agree to use acceptable contraception during their participation in this study. Potential subjects must agree to avoid the following during their participation in this study: * participation in any other nicotine-related modification strategy outside of this protocol; * use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco; * use of experimental (investigational) drugs or devices; * use of illegal drugs; * use of opiate medications; * consumption of grapefruit or grapefruit juice for the first six weeks of study participation; * use of melatonin; * use of sedating antihistamines for the first six weeks of study participation; * use of alcohol during the first six weeks of study participation. * use of benzodiazepines
Exclusion criteria
* Inability to attend all required experimental sessions; * Inability to take oral drugs or adhere to medication regimens; * Hypertension (systolic \>140 mm Hg, diastolic \>90 mm Hg); * Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg). * Coronary heart disease; * Lifetime history of heart attack; * Clinically significant cardiac rhythm disorder (irregular heart rhythm); * Chest pains; * Cardiac (heart) disorder; * Extensive active skin disorder; * Liver or kidney disorder; * Gastrointestinal disease other than gastroesophageal reflux or heartburn; * Active ulcers in the past 30 days; * Currently symptomatic lung disorder/disease; * Brain abnormality; * Migraine headaches that occur more frequently than once per week; * History of seizures; * Recent, unexplained fainting spells; * Problems giving blood samples; * Diabetes (unless treated with diet and exercise alone); * Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer); * Other major medical condition; * Current symptomatic psychiatric disease; * Current depression; * Current suicidal ideation or history of suicide attempt (in the past 5 years); * Pregnant or nursing mothers; * Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive), * Experimental (investigational) drugs; * Psychiatric medications including antidepressants, antipsychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Corticosteroids; * Cytochrome P450 341 (CYP3A4) inhibitors and inducers; * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes; * Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine replacement therapy or any other smoking cessation aid. * Use (within the past 14 days) of: * dehydroepiandrosterone (DHEA), Pregnenolone or ganaxolone; * Opiate medications for pain or sleep; * Benzodiazepines or other drugs with significant sedating or anticholinergic activity; * Use of more than one cigar a month; * Regular alcohol use; * Significant adverse reaction to nicotine patches in the past. * Significant past adverse reaction to ganaxolone in the past. * Current participation or recent participation (in the past 30 days) in another smoking study at our center or another research facility. * Current participation in another research study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 2 | Baseline and 2 Weeks | To evaluate the effects of ganaxolone on ad lib smoking by looking at the percent change in expired air CO at the end of week two (relative to baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 4 | Baseline and 4 Weeks | To evaluate the effects of ganaxolone as an augmentation treatment in conjunction with nicotine patch by looking at the percent change in expired air CO at the end of week four (relative to baseline). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Completing Continuous 2-week Abstinence From Smoking | 2 Weeks post quit | Continuous two week abstinence from smoking at the first post-quit visit (approximately 2 weeks post quit date), based on self-reported abstinence confirmed by expired air CO. |
| Number of Participants Completing Point Abstinence From Smoking Two Weeks After Quitting | 7 day point abstinence from smoking at 2 weeks post quit | Point abstinence from smoking two weeks post quit, based on self-reported abstinence during last seven days confirmed by expired air CO at first post-quit visit. |
| Number of Participants Completing Continuous 6-week Abstinence From Smoking | 6 Weeks post quit | Continuous six week abstinence from smoking at final study visit (approximately 6 weeks post quit date), based on self-reported abstinence confirmed by expired air CO |
| Number of Participants Completing Abstinence From Smoking During the Last Four Weeks of Treatment | 4 Week abstinence from smoking at 6 weeks post quit | End of treatment abstinence from smoking during the last four weeks of treatment, based on self-reported abstinence during last four weeks confirmed by expired air CO |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ganaxolone -- Nicotine Patch Pre-Quit Period:
Ganaxolone -- 400mg daily for the first 3 days, 800mg daily for the next 3 days and 1200mg daily for the remainder of the first 2 wks.
Nicotine Patches -- 21mg/24h nicotine patches applied daily during wks. 3 and 4.
Post-Quit Period:
Ganaxolone -- 1200mg daily for wk. 5, 800mg daily for 3 days, and 400mg daily for 3 days.
Nicotine Patches -- 21mg/24h for 4 wks., 14mg/24h for 1 wk., and 7mg/24h for 1 wk. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Ganaxolone -- Nicotine Patch |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 47.44 years STANDARD_DEVIATION 9.94 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 2
To evaluate the effects of ganaxolone on ad lib smoking by looking at the percent change in expired air CO at the end of week two (relative to baseline).
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ganaxolone -- Nicotine Patch | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 2 | -0.52 percentage change | Standard Error 7.38 |
Secondary
Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 4
To evaluate the effects of ganaxolone as an augmentation treatment in conjunction with nicotine patch by looking at the percent change in expired air CO at the end of week four (relative to baseline).
Time frame: Baseline and 4 Weeks
Population: Three of the original 16 subjects dropped out prior to week 4, so only 13 subjects had a week 4 CO reading and could be included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ganaxolone -- Nicotine Patch | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 4 | -39.40 percentage change | Standard Error 8.96 |
Other Pre-specified
Number of Participants Completing Abstinence From Smoking During the Last Four Weeks of Treatment
End of treatment abstinence from smoking during the last four weeks of treatment, based on self-reported abstinence during last four weeks confirmed by expired air CO
Time frame: 4 Week abstinence from smoking at 6 weeks post quit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganaxolone -- Nicotine Patch | Number of Participants Completing Abstinence From Smoking During the Last Four Weeks of Treatment | 5 participants |
Other Pre-specified
Number of Participants Completing Continuous 2-week Abstinence From Smoking
Continuous two week abstinence from smoking at the first post-quit visit (approximately 2 weeks post quit date), based on self-reported abstinence confirmed by expired air CO.
Time frame: 2 Weeks post quit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganaxolone -- Nicotine Patch | Number of Participants Completing Continuous 2-week Abstinence From Smoking | 3 participants |
Other Pre-specified
Number of Participants Completing Continuous 6-week Abstinence From Smoking
Continuous six week abstinence from smoking at final study visit (approximately 6 weeks post quit date), based on self-reported abstinence confirmed by expired air CO
Time frame: 6 Weeks post quit
Population: Because 6-week abstinence is counted backward from the final study visit, one additional subject (n=4) qualified as abstinent than at 2-weeks post-quit (n=3) due to the fact that the day(s) that one of the subjects smoked did not fall into the range evaluated at 6 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganaxolone -- Nicotine Patch | Number of Participants Completing Continuous 6-week Abstinence From Smoking | 4 participants |
Other Pre-specified
Number of Participants Completing Point Abstinence From Smoking Two Weeks After Quitting
Point abstinence from smoking two weeks post quit, based on self-reported abstinence during last seven days confirmed by expired air CO at first post-quit visit.
Time frame: 7 day point abstinence from smoking at 2 weeks post quit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganaxolone -- Nicotine Patch | Number of Participants Completing Point Abstinence From Smoking Two Weeks After Quitting | 4 participants |