Restoring Cognitive Control (ReCon) in Acute Nicotine Withdrawal

NCT03887429 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PRO-202
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

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.

Conditions

Impulse Control Disorders

Keywords

SXC-2023; Cognitive Control; Impulsivity; Delay Aversion; Top Down Processing; Behavioral Addiction

Outcome Measures

Primary Outcomes (7)

• 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.

  Up to 5 days

• 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.

  5 days

• 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.

  5 days

• 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.

  Up to 5 days.

• 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.

  Up to 5 days.

• 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.

  Up to 5 days.

• 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.

  Up to 5 days.

Other Outcomes (1)

• Levels of Glutathione (GSH) in Whole Blood Following 5 Days of Tobacco Abstinence.

  Up to 5 days.

Study Arms (4)

SXC-2023 200 mg followed by placebo

EXPERIMENTAL

SXC-2023 200mg dosed once daily for 5 days, followed by 9 day washout, then Placebo dosed once daily for 5 days.

Drug: SXC-2023; Drug: Placebos

Placebo followed by SXC-2023 200 mg

EXPERIMENTAL

Placebo dosed once daily for 5 days, followed by 9 day washout, then SXC-2023 200mg dosed once daily for 5 days.

Drug: SXC-2023; Drug: Placebos

SXC-2023 800 mg followed by placebo

EXPERIMENTAL

SXC-2023 800mg dosed once daily for 5 days, followed by 9 day washout, then Placebo dosed once daily for 5 days.

Drug: SXC-2023; Drug: Placebos

Placebo followed by SXC-2023 800 mg

EXPERIMENTAL

Placebo dosed once daily for 5 days, followed by 9 day washout, then SXC-2023 800mg dosed once daily for 5 days.

Drug: SXC-2023; Drug: Placebos

Interventions

SXC-2023 DRUG

SXC-2023 oral capsules

Placebo followed by SXC-2023 200 mg; Placebo followed by SXC-2023 800 mg; SXC-2023 200 mg followed by placebo; SXC-2023 800 mg followed by placebo

Placebos DRUG

Matching Placebo oral capsules

Placebo followed by SXC-2023 200 mg; Placebo followed by SXC-2023 800 mg; SXC-2023 200 mg followed by placebo; SXC-2023 800 mg followed by placebo

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult, female or male, 28-55 years of age, inclusive at screening.
• BMI ≥ 16.0 and ≤ 35.0 kg/m2 at screening.
• 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.
• Non-treatment seeking smokers regularly using tobacco with a FTND score ≥4 at screening and self-reported use of ≥10 cigarettes/day at screening.
• Has smoked for \>5 years at screening.
• Meets Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for tobacco use disorder.
• Must have a score ≥ 4 on the FTND and an expired-air CO level ≥10 ppm during initial screening and prior to first dose.
• 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.
• Female of non-childbearing potential: must have undergone one of the following sterilization procedures, at least 6 months prior to the first dose:
• hysteroscopic sterilization;
• bilateral tubal ligation or bilateral salpingectomy;
• hysterectomy;

You may not qualify if:

• 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.
• Subject suffered a concussion 6 months or less prior to screening.
• Females who are pregnant or breastfeeding.
• Positive for active hepatitis, human immunodeficiency virus (HIV), coagulopathy, or hepatic illness.
• 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.
• Use of antipsychotics or use of antiepileptics within 30 days prior to screening.
• Use of NAC within 30 days prior to screening.
• Use of Chantix or related smoking cessation medications (e.g., NicoDerm patch, Nicorette gum, etc) within 30 days prior to the first dose.
• Use of sulfasalazine (Azulfidine®) within 30 days prior to the first dose.
• DSM-5 criteria for alcohol/substance use disorder (except for tobacco use disorder).
• History or presence of clinically significant psychiatric condition (except for tobacco use disorder) or disease in the opinion of the PI or designee.
• 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.
• History of seizures.
• Any history of psychiatric hospitalization in the past year.
• Currently participating in a clinical study.

Sponsors & Collaborators

• Promentis Pharmaceuticals, Inc.: lead
• Celerion: collaborator
• Baylor College of Medicine: collaborator

Study Sites (2)

Celerion Inc.

Lincoln, Nebraska, 68502, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Disruptive, Impulse Control, and Conduct Disorders; Impulsive Behavior

Condition Hierarchy (Ancestors)

Mental Disorders; Behavior

Results Point of Contact

• Title: Chad Beyer
• Organization: Promentis Pharmaceuticals

cbeyer@promentispharma.com

(414) 238 2992

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 25, 2019
• Study Start: March 4, 2019
• Primary Completion: July 2, 2019
• Study Completion: July 9, 2019
• Last Updated: July 17, 2020
• Results First Posted: July 17, 2020

Record last verified: 2020-07

Locations

US (2)