Does CERC-501 Attenuate Stress-precipitated Smoking Lapse?

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 out-patient testing day on Day 8. Subjects will participate in a laboratory session following the McKee Stress-Smoking Lapse Test. Upon completion, subjects will undergo a 7 day washout period followed by the second period of the crossover design and a 7-day follow-up visit.

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
• Smokes at least 10 cigarettes per day on average for the past 6 months
• Fagerstrom score ≥3 at screening
• Currently not seeking smoking cessation therapy
• Urine dip test for cotinine concentration >150 ng/mL
• In otherwise good general health without any unstable medical conditions (as determined by medical history, medication history, physical examination, 10- or 12 lead ECG, vital signs, and clinical laboratory testing)
• Able to read, write, and speak 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:

i. Uses an acceptable double-barrier method of contraception as determined by the Investigator -and- ii. 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

• Have used tobacco or other nicotine containing products other than cigarettes (e.g., nicotine patches, pipe, cigars, snuff, chewing tobacco or e-cigarettes) within the past 30 days
• Any substance use disorder other than nicotine or caffeine as assessed by the Structured Clinical Interview-IV Axis I Disorders (SCID) for Diagnostic and Statistical Manual of Mental Disorders (DSM)
• 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 SCID-IV
• 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. We will screen for worsening of symptoms of depression and/or suicidality at each medication appointment and lab sessions by having participants complete the Beck Depression Inventory (BDI) and the Columbia-Suicide Severity Rating Scale (C-SSRS). If there is a worsening of symptoms of depression and/or suicidality, the participants will speak a licensed psychologist for evaluation.
• 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 Study MD (i.e., poorly controlled diabetes mellitus, congestive heart failure, etc.)
• Clinically significant clinical laboratory test taken during screening
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (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
• Positive ethanol breath test at screening or prior to dosing on Days 1 and 8 of each treatment period
• Positive urine drug test at screening or and/or prior to dosing on Days 1 and 8 of each treatment period except for cannabis
• 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
• 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
• Current use of any psychoactive medications including: antipsychotics, benzodiazepines, mood stabilizers, selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) or other antidepressants mood stabilizers