Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a
Condition: ANXIETY DISORDERS (or Anxiety and Phobic Neuroses)
MeSH terms: Anxiety Disorders; Phobic Disorders
Intervention: CERC-501; placebo
Intervention description: Oral dosing of 10 mg CERC-501 daily for 8 weeks; oral dosing of 10 mg placebo daily for 8 weeks
Intervention MeSH terms: Aticaprant; Narcotic Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 163.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Anhedonia; Mood and Anxiety Spectrum Disorders; CERC-501 (investigational product); Kappa Opioid Receptor (KOR)

Summary:

      The available treatment for patients with mood and anxiety disorders have significant
      limitations (Rush, 2007; Denys and de Geus, 2005). There is a need to develop new treatments
      for people with these disorders. Many research studies carried out in animals and a few
      preliminary studies carried out in humans suggest that medications which block kappa opioid
      receptors (KOR) have potential for being effective new treatments for patients with mood and
      anxiety spectrum disorders. These medications have shown particular promise for improving one
      important type of difficulty experienced by many patients who suffer from mood and anxiety
      spectrum disorders referred to as anhedonia, which is an impairment in reward-related
      function. In this study we will test the hypothesis that KOR antagonism is a promising means
      of improving anhedonia in patients with mood and anxiety spectrum disorders. We will do so by
      evaluating whether we can establish Proof of Concept (POC) that a relatively selective KOR
      antagonist, CERC-501 (formerly known as LY2456302), engages neural circuits involved in
      mediating reward-related function in patients with mood and anxiety spectrum disorders with
      anhedonia. We are attempting to establish POC in this study in order to determine whether
      there is a sufficient basis for pursuing future work evaluating whether KOR antagonism has
      therapeutic effects on clinical and behavioral measures of reward-related functioning.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age between 21 and 65 years of age

          -  Must meet DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders, 4th
             edition, text revision) diagnostic criteria for: Major Depressive Disorder, Bipolar I
             or II Depressed, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, or Post
             Traumatic Stress Disorder

          -  Snaith-Hamilton Pleasure Scale (SHAPS) score ≥ 20

          -  Reliable and willing to be available for the duration of the study

          -  Willing and able to give written informed consent to participate

          -  Able to understand and comply with instructions

          -  If female of childbearing potential, must agree to use dual methods of contraception
             and be willing and able to continue contraception for 6 weeks after the last dose of
             study drug. Females using oral contraception must have started using it at least 2
             months prior to the Baseline Visit

          -  If male of childbearing potential, must have undergone surgical sterilization (such as
             a vasectomy) or agree to use a condom used with a spermicide during participation in
             the study and for 1 month afterward

        Exclusion Criteria:

          -  Expected to require hospitalization during the course of the study

          -  Current/history of a psychotic disorder, current manic or mixed episode, autism
             spectrum disorders, mental retardation

          -  Met DSMIV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text
             revision) criteria for substance abuse within the last 3 months or substance
             dependence within the last 6 months, excluding caffeine and/or nicotine

          -  History of unstable or untreated serious medical condition based on physician
             evaluation, medical history, and screening laboratory testing

          -  Active suicidal intent or plan, or history of attempt within the past 3 months based
             on physician evaluation and Columbia Suicide Severity Rating Scale (C-SSRS)

          -  Use of any antidepressant, antipsychotic, anxiolytic, anticonvulsant, mood
             stabilizing, muscle relaxant, centrally acting antihistaminergic, stimulant or
             insomnia medications (See Appendix 2) within 5 half-lives of baseline or at any time
             during after baseline

          -  Use of any medication that is primarily metabolized by Cytochrome P450 2C8 within 14
             days of baseline or at any time during the study. This includes: Cerivastatin,
             Paclitaxel, Repaglinide, Sorafenib, Rosiglitazone, Trimethoprim, Amodiaquine,
             Morphine, Amiodarone, Cabazitaxel, Carbamazepine, Chloroquine, Ibuprofen, Trepostinil,
             Torsemide.

          -  Any contraindications to the magnetic resonance imaging procedures

          -  Positive urine drug screen at any time during the study

          -  Use of any investigational medication within 3 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

          -  Known hypersensitivity to CERC-501 (formerly known as LY2456302)

          -  History of severe allergies or multiple adverse drug reactions

          -  History of gastric disease (including peptic ulcer disease, gastritis, upper GI
             bleeding, or any GI precancerous condition), current clinically evident
             gastrointestinal complaints, or positive urea breath test

          -  Current use of a proton pump inhibitor or histamine 2 blocker, or a history of chronic
             NSAID (nonsteroidal anti-inflammatory drug) use.

          -  History of use of Salvia divinorum or use of Salvia divinorum at any time during the
             study.

          -  Any other condition that in the opinion of the investigator would preclude
             participation in the study

          -  Any smoking of cigarettes or use of other nicotine containing products within the last
             month or at any time during the study

          -  Pregnant or lactating