Clinical trial NCT03887429: Restoring Cognitive Control (ReCon) in Acute Nicotine Withdrawal
Official title: An Exploratory, Placebo-Controlled, Crossover Study to Examine the Safety and Activity of SXC-2023 to Improve Behavioral Dynamics in Non-Treatment Seeking Adults Undergoing Acute Nicotine Withdrawal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Impulse Control Disorders
Keywords: SXC-2023
Cognitive Control
Impulsivity
Delay Aversion
Top Down Processing
Behavioral Addiction
Lead sponsor: Promentis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Celerion
name: Baylor College of Medicine
First posted: 2019-03-25
Enrollment: 34
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability of SXC-2023.
timeFrame: Up to 5 days
measure: Activity of SXC-2023 on Impulsivity, Measured Using Stop Signal Task.
timeFrame: 5 days
measure: Activity of SXC-2023 on Risk Taking Behavior, as Measured Using Cambridge Gamblers Task - Delay Aversion Total.
timeFrame: 5 days
measure: Activity of SXC-2023 on Abstinence Induced Mood, Assessed by Positive and Negative Affect Schedule.
timeFrame: Up to 5 days.
measure: Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Questionnaire on Smoking Urges.
timeFrame: Up to 5 days.
measure: Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes, Assessed by Cigarette Evaluation Questionnaire.
timeFrame: Up to 5 days.
measure: Activity of SXC-2023 on Measures of Abstinence Induced Urge for Cigarettes and Mood, Assessed by Cue Reactivity and Likert Assessment.
timeFrame: Up to 5 days.
Secondary outcomes:
Other outcomes:
measure: Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence.
timeFrame: Up to 5 days.
Locations:
city: Lincoln
country: United States
facility: Celerion Inc.
state: Nebraska
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: