A Study in a Human Laboratory Model of Smoking Behavior

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Placebo-Controlled, Crossover Design Study of CERC-501 in a Human Laboratory Model of Smoking Behavior.

Detailed Description
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The study will be performed in subjects who are heavy cigarette smokers currently not seeking treatment for tobacco use disorder. The study is a crossover design study (within-subject analysis), which allows for subjects to be their own control. Each period of the crossover consists of a 7-day out-patient treatment period followed by a single in-patient testing day on Day 8. Subjects will participate in a laboratory session following the McKee Smoking Lapse Test and be discharged from the clinic to undergo a 7 day washout period followed by the second period of the crossover design and a 7-day follow-up visit.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Crossover Design Study of CERC-501 in a Human Laboratory Model of Smoking Behavior

Conditions
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Smoking

Intervention / Treatment
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* Drug: CERC-501
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provides written informed consent and agrees to complete required clinic visits Male or female 21 to 60 years of age inclusive Body mass index (BMI) 18.5 to 40 kg/m2 inclusive Heavy Smokers Currently not seeking smoking cessation therapy In otherwise good general health without any unstable medical conditions (as determined by medical history, medication history, physical examination, 12-lead ECG, vital signs, and clinical laboratory testing) Able to read, write, and speak in English Females must be either: Post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile -or- Women of childbearing potential (WOCBP) must meet the criteria below: Uses an acceptable double-barrier method of contraception as determined by the Investigator -and- Is not lactating, has a negative serum beta human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test prior to dosing on Days 1 and 8 of each treatment period. Male subjects must agree to use a condom if partner is of childbearing potential Exclusion Criteria: Subjects meeting the following criteria are not eligible for the study: Any substance use disorder other than nicotine or caffeine as assessed by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) substance use disorder checklist in addition to the Mini-International Neuropsychiatric Interview (MINI) (to capture both DSM-V substance use disorder diagnoses) Current neurological conditions that interfere with study conduct, assessment or treatment in any significant fashion Any lifetime history of bipolar I, II; schizophrenia or any other psychotic disorders; personality disorders, impulse control disorders as assessed by the MINI Current psychiatric conditions that interfere with study conduct, assessment or treatment in any significant fashion, such as major depressive disorder (MDD), eating disorders, post-traumatic stress disorder, etc., without permission of the medical monitor Recent active or past history of gastric disease such as peptic ulcer disease, gastritis, upper gastrointestinal bleeding, or any gastrointestinal malignancy or precancerous condition Active, comorbid disease that might limit the ability of the subject to participate in the study as determined by the Investigator (i.e., poorly controlled diabetes mellitus, congestive heart failure, etc.) Clinically significant clinical laboratory test taken during screening, without permission of the Medical Monitor Elevated AST or ALT ≥ 2 times the upper limit of normal (ULN) Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C positive as determined by serology testing at Screening History of severe allergies or multiple adverse drug reactions Known hypersensitivity to CERC-501 Current use of a proton pump inhibitor or histamine 2 blocker without permission of the Medical Monitor Use of any investigational medication within 2 months prior to the start of this study or scheduled to receive an investigational drug other than the study drug during the course of this study

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CERC-501<br>Administered orally once daily, 15mg daily, 8 days. | Drug: CERC-501<br>* CERC-501<br>|
| Placebo Comparator: Placebo<br>Administered orally daily, 8 days. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Latency | Latency (in minutes and seconds) to time of first cigarette smoked during the delay period | 50 min | 
| Number of Cigarettes smoked | Number of cigarettes smoked during the self administration period | 60 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tobacco Craving | Tobacco craving assessed by the Tiffany Questionnaire of Smoking Urges-Brief (QSU-Brief) prior to tobacco withdrawal (Day 7 of each Period) and prior to reinstatement of tobacco (Day 8 of each period) | Up to 4 days ( 2 each period) | 
| Mood Scores | Mood Scores (Circumplex) prior to tobacco withdrawal (Day 7 of each Period) and prior to reinstatement of tobacco (Day 8 of each period) | Up to 4 days ( 2 each period) | 
| Nicotine Withdrawal | Nicotine withdrawal scores will be assessed by the Minnesota Nicotine Withdrawal Scale (MNWS) prior to tobacco withdrawal (Day 7 of each Period) and prior to reinstatement of tobacco (Day 8 of each period) | Up to 4 days ( 2 each period) | 
| Anxiety Scores | Anxiety Scores will be assessed by the Clinically Useful Depression Outcome Scale Modified for Anxious distress (CUDOS-A) prior to tobacco withdrawal (Day 7 of each Period) and prior to reinstatement of tobacco (Day 8 of each period) | Up to 4 days ( 2 each period) | 
| Subject Feeling | Subject feelings of positive and negative effect of tobacco as assessed by the Modified Cigarette Evaluation Questionnaire (mCEQ) prior to tobacco withdrawal (Day 7 of each Period) and prior to reinstatement of tobacco (Day 8 of each period) | Up to 4 days ( 2 each period) | 
| Electronic Diary | Daily Smoking Diary for out-patient periods | up to 51 days |