Impulse Control Disorders
Conditions
Keywords
SXC-2023, Cognitive Control, Impulsivity, Delay Aversion, Top Down Processing, Behavioral Addiction
Brief summary
The purpose of this study is to explore the safety, tolerability and activity of SXC-2023 or placebo when dosed for 5 days in adults with tobacco use disorder who voluntarily abstain from the use of cigarettes.
Detailed description
This study is a Phase 2A, randomized, double-blinded, placebo-controlled, two-period crossover study to evaluate the effect of two doses of SXC-2023 on measures of impulsivity and inhibitory control, urge for cigarettes, and mood in non-treatment seeking smokers who are abstaining from smoking. The study consists of a screening period of up to 30 days, a 5 day randomized double-blind treatment period, a 9 day washout period, followed by a second 5 day randomized double-blind treatment period, with a safety follow-up period 7 days after the last dose of study medication.
Interventions
DRUGSXC-2023
SXC-2023 oral capsules
DRUGPlacebos
Matching Placebo oral capsules
Sponsors
Celerion
Baylor College of Medicine
Promentis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Adult, female or male, 28-55 years of age, inclusive at screening. 2. BMI ≥ 16.0 and ≤ 35.0 kg/m2 at screening. 3. Has provided signed written informed consent and has willingness and ability to comply with all aspects of the protocol, including abstaining from the use of tobacco/nicotine products for two 5-day periods. 4. Non-treatment seeking smokers regularly using tobacco with a FTND score ≥4 at screening and self-reported use of ≥10 cigarettes/day at screening. 5. Has smoked for \>5 years at screening. 6. Meets Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for tobacco use disorder. 7. Must have a score ≥ 4 on the FTND and an expired-air CO level ≥10 ppm during initial screening and prior to first dose. 8. For a female of childbearing potential: either be sexually inactive (abstinent as a life style) for 28 days prior to the first dosing and throughout the study or be using one of the following acceptable birth control methods: * Oral contraceptives used for at least 3 months prior to the first dose. * Non-hormone releasing intrauterine device for at least 3 months prior to the first dose and with either a physical (e.g., condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the time of screening and throughout the study. * Double physical barrier method (e.g., condom and diaphragm) from 14 days prior to the first dose and throughout the study. 9. Female of non-childbearing potential: must have undergone one of the following sterilization procedures, at least 6 months prior to the first dose: 1. hysteroscopic sterilization; 2. bilateral tubal ligation or bilateral salpingectomy; 3. hysterectomy; 4. bilateral oophorectomy; Or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with serum follicle stimulating hormone levels consistent with postmenopausal status or have medically documented history of biological or congenital sterility. 10. Has not used Aricept 30 days prior to screening.
Exclusion criteria
1. Subject is mentally or legally incapacitated or has significant emotional problems or clinically significant abnormality at the time of the screening visit or expected during the conduct of the study. 2. Subject suffered a concussion 6 months or less prior to screening. 3. Females who are pregnant or breastfeeding. 4. Positive for active hepatitis, human immunodeficiency virus (HIV), coagulopathy, or hepatic illness. 5. Use of Selective Serotonin or Norepinephrine Reuptake Inhibitors for psychiatric illness (e.g. depression, anxiety, etc.), unless subject has been on a stable dose for at least 30 days prior to screening. 6. Use of antipsychotics or use of antiepileptics within 30 days prior to screening. 7. Use of NAC within 30 days prior to screening. 8. Use of Chantix or related smoking cessation medications (e.g., NicoDerm patch, Nicorette gum, etc) within 30 days prior to the first dose. 9. Use of sulfasalazine (Azulfidine®) within 30 days prior to the first dose. 10. DSM-5 criteria for alcohol/substance use disorder (except for tobacco use disorder). 11. History or presence of clinically significant psychiatric condition (except for tobacco use disorder) or disease in the opinion of the PI or designee. 12. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study. 13. History of seizures. 14. Any history of psychiatric hospitalization in the past year. 15. Currently participating in a clinical study. 16. Previously participated in any Phase 1 Promentis studies or dosed in this Phase 2A study. 17. FTND score \<4 and expelled CO levels \<10 ppm at screening and prior to first dose. 18. Any clinically significant laboratory, ECG and/or vital sign abnormalities at screening. 19. Unable to read/understand/speak English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Up to 5 days. | Outcome to be measured using two scores, the first ranging from 10-70, with a higher score indicating a stronger urge to smoke, and the second score ranging from 10-80, with a higher score indicating a more positive mood. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment. |
| Safety and Tolerability of SXC-2023. | Up to 5 days | Endpoint assessed using the frequency of serious adverse events, adverse events leading to discontinuation, and adverse events judged to be related to study medication. |
| Activity of SXC-2023 on Impulsivity, Measured Using Stop Signal Task. | 5 days | Stop Signal Reaction Time (SSRT) assesses the length of reaction time between a 'go' stimulus and a 'stop' stimulus at which the subject is able to inhibit their motor response 50% of the time. The scale is from 0-1500 milliseconds with a lower value showing reduced motor impulsivity. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment, and the change in subject scores was assessed. |
| Activity of SXC-2023 on Risk Taking Behavior, as Measured Using Cambridge Gamblers Task - Delay Aversion Total. | 5 days | Cambridge Gamblers Task measures risk taking behavior using a score from -1 to 1, with a higher value showing increased impulsivity. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment and change in score assessed. |
| Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | Up to 5 days. | Outcome to be measured using two scores ranging from 10-50, with a higher score indicating a more positive affect, and a lower score indicating a more negative affect. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment. |
| Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | Up to 5 days. | Outcome to be measured using a score ranging from 10-70, with a higher score indicating a higher urge for a cigarette. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment. |
| Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Up to 5 days. | Outcome to be measured using five scores ranging from 1-7 and corresponding to Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations and Craving Reduction. A higher score indicates a greater intensity of the associated sensation. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence. | Up to 5 days. | Levels total and/or reduced of GSH in whole blood will be collected at baseline (prior to dosing on Day 1) and after 5 days of tobacco abstinence (after dosing on Day 5). Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SXC-2023 200 mg Followed by Placebo SXC-2023 200mg dosed once daily for 5 days, followed by 9 day washout, then Placebo dosed once daily for 5 days.
SXC-2023: SXC-2023 oral capsules
Placebos: Matching Placebo oral capsules | 8 |
| Placebo Followed by SXC-2023 200 mg Placebo dosed once daily for 5 days, followed by 9 day washout, then SXC-2023 200mg dosed once daily for 5 days.
SXC-2023: SXC-2023 oral capsules
Placebos: Matching Placebo oral capsules | 9 |
| SXC-2023 800 mg Followed by Placebo SXC-2023 800mg dosed once daily for 5 days, followed by 9 day washout, then Placebo dosed once daily for 5 days.
SXC-2023: SXC-2023 oral capsules
Placebos: Matching Placebo oral capsules | 9 |
| Placebo Followed by SXC-2023 800 mg Placebo dosed once daily for 5 days, followed by 9 day washout, then SXC-2023 800mg dosed once daily for 5 days.
SXC-2023: SXC-2023 oral capsules
Placebos: Matching Placebo oral capsules | 8 |
| Total | 34 |
Baseline characteristics
| Characteristic | Total | Placebo Followed by SXC-2023 800 mg | SXC-2023 800 mg Followed by Placebo | Placebo Followed by SXC-2023 200 mg | SXC-2023 200 mg Followed by Placebo |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 8 Participants | 9 Participants | 9 Participants | 8 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 8.2 | 41 years STANDARD_DEVIATION 9.5 | 39 years STANDARD_DEVIATION 7.7 | 44 years STANDARD_DEVIATION 8.5 | 45 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 8 Participants | 9 Participants | 9 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United States | 34 participants | 8 participants | 9 participants | 9 participants | 8 participants |
| Sex: Female, Male Female | 18 Participants | 4 Participants | 5 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 16 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 31 |
| other Total, other adverse events | 5 / 16 | 3 / 16 | 13 / 31 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 31 |
Outcome results
Primary
Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule.
Outcome to be measured using two scores ranging from 10-50, with a higher score indicating a more positive affect, and a lower score indicating a more negative affect. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment.
Time frame: Up to 5 days.
Population: Subjects who did not complete treatment with both placebo and SXC-2023 were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | SXC-2023 Change in Positive Aspect | 3.5 score on a scale | Standard Deviation 8.2 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | Placebo Change in Positive Aspect | 2.0 score on a scale | Standard Deviation 7.43 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | SXC-2023 Change in Negative Aspect | -.9 score on a scale | Standard Deviation 5.01 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | Placebo Change in Negative Aspect | -.7 score on a scale | Standard Deviation 3.93 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | Placebo Change in Negative Aspect | .1 score on a scale | Standard Deviation 5.02 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | SXC-2023 Change in Positive Aspect | 2.1 score on a scale | Standard Deviation 7 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | SXC-2023 Change in Negative Aspect | -1.2 score on a scale | Standard Deviation 2.61 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule. | Placebo Change in Positive Aspect | 3.3 score on a scale | Standard Deviation 6.5 |
Primary
Activity of SXC-2023 on Impulsivity, Measured Using Stop Signal Task.
Stop Signal Reaction Time (SSRT) assesses the length of reaction time between a 'go' stimulus and a 'stop' stimulus at which the subject is able to inhibit their motor response 50% of the time. The scale is from 0-1500 milliseconds with a lower value showing reduced motor impulsivity. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment, and the change in subject scores was assessed.
Time frame: 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Impulsivity, Measured Using Stop Signal Task. | 4.6901 milliseconds | Standard Deviation 6.7368 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Impulsivity, Measured Using Stop Signal Task. | -1.757 milliseconds | Standard Deviation 6.8491 |
| During Placebo Treatment | Activity of SXC-2023 on Impulsivity, Measured Using Stop Signal Task. | 3.956 milliseconds | Standard Deviation 3.9661 |
Comparison: It was hypothesized that treatment with SXC-2023 would reduce impulsivity as measured by SSRT in chronic cigarette smokers abstaining from nicotine for 5 days.p-value: =0.009t-test, 1 sided
Primary
Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment.
Outcome to be measured using two scores, the first ranging from 10-70, with a higher score indicating a stronger urge to smoke, and the second score ranging from 10-80, with a higher score indicating a more positive mood. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment.
Time frame: Up to 5 days.
Population: Subjects who did not complete treatment with both placebo and SXC-2023 were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Neutral Urge | .353 units on a scale | Standard Deviation 1.7932 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Neutral Urge | -.142 units on a scale | Standard Deviation 1.5071 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Neutral Mood | 1.058 units on a scale | Standard Deviation 1.3775 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Neutral Mood | .602 units on a scale | Standard Deviation 1.7237 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Positive Urge | .5 units on a scale | Standard Deviation 1.922 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Positive Urge | -.12 units on a scale | Standard Deviation 1.543 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Positive Mood | 1.23 units on a scale | Standard Deviation 1.509 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Positive Mood | .73 units on a scale | Standard Deviation 1.666 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Smoking Urge | .39 units on a scale | Standard Deviation 2.105 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Smoking Urge | -.65 units on a scale | Standard Deviation 1.864 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Smoking Mood | .42 units on a scale | Standard Deviation 1.352 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Smoking Mood | .88 units on a scale | Standard Deviation 1.431 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Smoking Mood | 1.65 units on a scale | Standard Deviation 1.796 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Neutral Urge | -.052 units on a scale | Standard Deviation 1.8934 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Positive Mood | 1.35 units on a scale | Standard Deviation 2.065 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Neutral Urge | -.173 units on a scale | Standard Deviation 1.5458 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Smoking Urge | -.27 units on a scale | Standard Deviation 1.653 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Neutral Mood | 1.667 units on a scale | Standard Deviation 1.6004 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Positive Mood | 1.38 units on a scale | Standard Deviation 1.557 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Neutral Mood | 1.192 units on a scale | Standard Deviation 1.476 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Smoking Mood | 1 units on a scale | Standard Deviation 1.339 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Positive Urge | .12 units on a scale | Standard Deviation 1.793 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | SXC-2023 change in Smoking Urge | -.23 units on a scale | Standard Deviation 1.549 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment. | Placebo change in Positive Urge | -.04 units on a scale | Standard Deviation 1.547 |
Primary
Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire.
Outcome to be measured using five scores ranging from 1-7 and corresponding to Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations and Craving Reduction. A higher score indicates a greater intensity of the associated sensation. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment.
Time frame: Up to 5 days.
Population: Complications with application of scales prevented collection of data from the majority of subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Satisfaction | .1 units on a scale | Standard Deviation 1.28 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Satisfaction | .3 units on a scale | Standard Deviation 0.33 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Psychological reward | .16 units on a scale | Standard Deviation 1.315 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Psychological reward | .8 units on a scale | Standard Deviation 0.693 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Aversion | .7 units on a scale | Standard Deviation 1.396 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Aversion | 0 units on a scale | Standard Deviation 0 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Enjoyment of Sensation | 0 units on a scale | Standard Deviation 1.58 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Enjoyment of Sensation | 0 units on a scale | Standard Deviation 2 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Craving Reduction | -.4 units on a scale | Standard Deviation 1.14 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Craving Reduction | -.7 units on a scale | Standard Deviation 2.08 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Enjoyment of Sensation | .8 units on a scale | Standard Deviation 0.96 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Satisfaction | .4 units on a scale | Standard Deviation 0.51 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Aversion | .63 units on a scale | Standard Deviation 0.946 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Satisfaction | -.2 units on a scale | Standard Deviation 0.69 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Craving Reduction | 0 units on a scale | Standard Deviation 1.41 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Psychological reward | .33 units on a scale | Standard Deviation 0.808 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Enjoyment of Sensation | 1.3 units on a scale | Standard Deviation 1.53 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | Placebo change in Psychological reward | -.2 units on a scale | Standard Deviation 1.071 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Craving Reduction | .3 units on a scale | Standard Deviation 0.58 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire. | SXC-2023 change in Aversion | 0 units on a scale | Standard Deviation 0 |
Primary
Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges.
Outcome to be measured using a score ranging from 10-70, with a higher score indicating a higher urge for a cigarette. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment.
Time frame: Up to 5 days.
Population: Subjects who did not complete treatment with both placebo and SXC-2023 were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | SXC-2023 Change in Anticipation of Pleasure | -.3 units on a scale | Standard Deviation 1.155 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | Placebo change in Anticipation of Pleasure | -.04 units on a scale | Standard Deviation 1.1236 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | SXC-2023 change in Anticipation of Relief | .14 units on a scale | Standard Deviation 1.201 |
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | Placebo change in Anticipation of Relief | -.06 units on a scale | Standard Deviation 0.946 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | Placebo change in Anticipation of Relief | .46 units on a scale | Standard Deviation 0.794 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | SXC-2023 Change in Anticipation of Pleasure | .64 units on a scale | Standard Deviation 1.332 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | SXC-2023 change in Anticipation of Relief | .21 units on a scale | Standard Deviation 1.214 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges. | Placebo change in Anticipation of Pleasure | .17 units on a scale | Standard Deviation 0.848 |
Primary
Activity of SXC-2023 on Risk Taking Behavior, as Measured Using Cambridge Gamblers Task - Delay Aversion Total.
Cambridge Gamblers Task measures risk taking behavior using a score from -1 to 1, with a higher value showing increased impulsivity. Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment and change in score assessed.
Time frame: 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Activity of SXC-2023 on Risk Taking Behavior, as Measured Using Cambridge Gamblers Task - Delay Aversion Total. | .03236 units on a scale | Standard Deviation 0.02652 |
| During 800 mg SXC-2023 Treatment | Activity of SXC-2023 on Risk Taking Behavior, as Measured Using Cambridge Gamblers Task - Delay Aversion Total. | .01358 units on a scale | Standard Deviation 0.02655 |
| During Placebo Treatment | Activity of SXC-2023 on Risk Taking Behavior, as Measured Using Cambridge Gamblers Task - Delay Aversion Total. | .03931 units on a scale | Standard Deviation 0.01569 |
Comparison: It was hypothesized that 5 days of nicotine abstinence in chronic cigarette smokers would result in increased risk taking behavior as measured using DAVT in subjects receiving placebo as treatment.p-value: =0.015t-test, 1 sided
Comparison: It was hypothesized that 5 days of nicotine abstinence in chronic cigarette smokers would not result in increased risk taking behavior as measured using DAVT in subjects treated with SXC-2023.p-value: >0.1t-test, 1 sided
Primary
Safety and Tolerability of SXC-2023.
Endpoint assessed using the frequency of serious adverse events, adverse events leading to discontinuation, and adverse events judged to be related to study medication.
Time frame: Up to 5 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Safety and Tolerability of SXC-2023. | AEs leading to study discontinuation | 0 Events |
| During 200 mg SXC-2023 Treatment | Safety and Tolerability of SXC-2023. | SAEs | 0 Events |
| During 200 mg SXC-2023 Treatment | Safety and Tolerability of SXC-2023. | AEs judged to be related to study drug. | 3 Events |
| During 800 mg SXC-2023 Treatment | Safety and Tolerability of SXC-2023. | AEs leading to study discontinuation | 0 Events |
| During 800 mg SXC-2023 Treatment | Safety and Tolerability of SXC-2023. | SAEs | 0 Events |
| During 800 mg SXC-2023 Treatment | Safety and Tolerability of SXC-2023. | AEs judged to be related to study drug. | 1 Events |
| During Placebo Treatment | Safety and Tolerability of SXC-2023. | SAEs | 0 Events |
| During Placebo Treatment | Safety and Tolerability of SXC-2023. | AEs judged to be related to study drug. | 12 Events |
| During Placebo Treatment | Safety and Tolerability of SXC-2023. | AEs leading to study discontinuation | 0 Events |
Other Pre-specified
Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence.
Levels total and/or reduced of GSH in whole blood will be collected at baseline (prior to dosing on Day 1) and after 5 days of tobacco abstinence (after dosing on Day 5). Subject scores were collected pre-dose on day 1 of treatment and post-dose on day 5 of treatment.
Time frame: Up to 5 days.
Population: Subjects who did not complete treatment with both placebo and SXC-2023 were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| During 200 mg SXC-2023 Treatment | Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence. | SXC-2023 change in GSH concentration | -3.45 μg/mL | Standard Deviation 23.318 |
| During 200 mg SXC-2023 Treatment | Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence. | Placebo change in GSH concentration | -5.13 μg/mL | Standard Deviation 21.826 |
| During 800 mg SXC-2023 Treatment | Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence. | SXC-2023 change in GSH concentration | -20.6 μg/mL | Standard Deviation 73.23 |
| During 800 mg SXC-2023 Treatment | Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence. | Placebo change in GSH concentration | -5.12 μg/mL | Standard Deviation 23.587 |