Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a

NCT02218736 | Completed Phase 2 Results DMC

• 2 other identifiers: Pro00052485HHSN271201200006I
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

ANXIETY DISORDERS (or Anxiety and Phobic Neuroses)

Keywords

Anhedonia; Mood and Anxiety Spectrum Disorders; CERC-501 (investigational product); Kappa Opioid Receptor (KOR)

Outcome Measures

Primary Outcomes (1)

• Change in Ventral Striatal Activation Occurring in Anticipation of Reward During the Monetary Incentive Delay Task Measured by fMRI

  Establish POC (Proof of Concept) for KOR (Kappa Opioid Receptor) antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI (Functional magnetic resonance imaging). The BOLD (Blood Oxygen Level-Dependent) score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.

  baseline, Week 8

Secondary Outcomes (2)

• Clinical Anhedonia Measured by the Snaith-Hamilton Pleasure Scale (SHAPS; Total Score)

  8 weeks

• Change in Behavioral Measure of Anhedonia Using the Probabilistic Reward Task

  baseline, Week 8

Study Arms (2)

CERC-501

EXPERIMENTAL

Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks

Drug: CERC-501

Placebo

PLACEBO COMPARATOR

Oral daily administration of 10 mg placebo for 8 weeks

Drug: placebo

Interventions

CERC-501 DRUG

Oral dosing of 10 mg CERC-501 daily for 8 weeks

Also known as: Kappa Opioid Receptor Antagonist; LY2456302

CERC-501

placebo DRUG

oral dosing of 10 mg placebo daily for 8 weeks

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Yale University: collaborator
• Baylor College of Medicine: collaborator
• Indiana University: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• Case Western Reserve University: collaborator

Study Sites (6)

Yale University

New Haven, Connecticut, 06510, United States

Location

Andrew Goddard, MD

Indianapolis, Indiana, 46202-l7176, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

CaseWestern Reserve University

Cleveland, Ohio, 44106, United States

Location

Baylor College of Medicine

Houston, Texas, 70030, United States

Location

Related Publications (1)

• Rorick-Kehn LM, Witkin JM, Statnick MA, Eberle EL, McKinzie JH, Kahl SD, Forster BM, Wong CJ, Li X, Crile RS, Shaw DB, Sahr AE, Adams BL, Quimby SJ, Diaz N, Jimenez A, Pedregal C, Mitch CH, Knopp KL, Anderson WH, Cramer JW, McKinzie DL. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology. 2014 Feb;77:131-44. doi: 10.1016/j.neuropharm.2013.09.021. Epub 2013 Sep 23.

  PMID: 24071566 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Phobic Disorders; Anhedonia

Interventions

Aticaprant

Condition Hierarchy (Ancestors)

Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Kathy Hijek, Associate Director of Clinical Operations
• Organization: Duke Clnical Research Institute

kathy.hijek@duke.edu

919-668-8700

Study Officials

• Richard D Weiner, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 18, 2014
• Study Start: June 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 8, 2019
• Results First Posted: January 8, 2019

Record last verified: 2018-12

Locations

US (6)