FASTMAS (Fast-Fail Trials in Mood and Anxiety Spectrum Disorders) Kappa Opioid Receptor Phase 1 Study

NCT02218775 | Withdrawn Phase 1 DMC

• 2 other identifiers: Pro00052483HHSN271201200006I
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The available treatments for patients with mood and anxiety spectrum disorders have significant limitations. This study will contribute significantly to public health by taking steps to address these limitations by aiding in the interpretation of a study that: 1) tests a promising new treatment for mood and anxiety spectrum disorders; 2) evaluates a potential target in the brain which could serve as the basis for development of additional new candidate compounds for the treatment of patients with mood and anxiety spectrum disorders; 3) establishes more expeditious methods for evaluating potential new therapies for patients with mood and anxiety spectrum disorders; and 4) specifically establishes methods for the development of new therapies targeting anhedonia, an important RDoC (Research Domain Criteria) endpoint.

Conditions

Anxiety Disorders

Keywords

Kappa opioid receptor; Mu opioid receptor; LY2456302; Anhedonia; Mood and Anxiety Spectrum Disorders

Outcome Measures

Primary Outcomes (3)

• Primary: Kappa opioid receptor occupancy determined with LY2879788 PET imaging; Mu opioid receptor occupancy determined with [11C]-Carfentanil PET imaging

  Baseline readings prior to drug dosing

  Both on Day 1

• Primary: Kappa opioid receptor occupancy determined with LY2879788 PET imaging; Mu opioid receptor occupancy determined with [11C]-Carfentanil PET imaging

  KOR occupancy using LY2879788 imaging at time of peak blood level of LY2456302 achieved with 2 weeks of daily dosing of 10 mg. LY2456302.

  Day 16: Trough LY2879788 PET Kappa Occupancy Study (22.5 hours after dosing)

• Peak PET Mu Occupancy

  Mu occupancy using \[11C\]-Carfentanil PET imaging at time of peal blood level of LY2456302 achieved with 2 weeks of daily dosing of 10 mg LY2456302

  Day 15

Secondary Outcomes (7)

• Reward Circuit Engagement Outcome

  Day 0

• Reward Circuit Engagement Outcome

  Day 14 (time of peak drug level)

• Clinical Anhedonia Outcome Utilizing the Snaith-Hamilton Pleasure Scale (SHAPS)

  Screening (Day -7 to Day -1)

• Clinical Anhedonia Outcome Utilizing the Snaith-Hamilton Pleasure Scale (SHAPS)

  Day 1

• Anhedonia Outcome Utilizing the Snaith-Hamilton Pleasure Scale (SHAPS)

  Day 15

Study Arms (1)

LY2456302

EXPERIMENTAL

LY2456302 dosed orally at 10 mg daily for 2 weeks in healthy volunteers

Drug: LY2456302

Interventions

LY2456302 DRUG

Mood and Anxiety Disorders

LY2456302

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21 through 65 years of age
• Body mass index 19 through 30 lbs/in2
• 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:

• Any clinically significant abnormality of any of the hematology, clinical, chemistry, or urine drug tests
• Magnetic resonance imaging contraindications at 3 Tesla (e.g., ferromagnetic implants or shrapnel or other incompatibilities)
• Any clinically significant abnormality of the 12-lead ECG; QTc (corrected QT) interval recorded on screening or predose greater than 450 msec
• Any clinically significant history of neurologic disease, cancer, or cardiac, respiratory, metabolic, hepatic, renal, gastrointestinal (except appendectomy), dermatological, venereal, hematological disorder or disease
• Any clinically significant history of Axis I psychiatric disorder, or history of attempted suicide
• History of seeking advice from a physician or counselor for abuse or misuse of alcohol, non-medical drugs, medicinal drugs or other substance abuse, for example, solvents
• Any current or previous recreational use of Class A drugs such as opiates, cocaine, ecstasy, LSD (Lysergic acid diethylamide), and amphetamines (Class B)
• Positive drugs-of-abuse test result at initial exam or at any time during the study
• An alcoholic intake greater than 7 units per week or unwillingness to stop alcohol consumption for the duration of the study {1 unit = 8 g ethanol (250 mL of beer, 1 glass wine \[100 mL\], 1 measure spirits \[30 mL\])}
• Use of prescribed medication within 30 days of the first study day, or nonprescription medication including herbal remedies except standard dose vitamin supplements and acetaminophen (up to 4 g/day) within 15 days of the first study drug administration, or any medication that would need to be continued 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 LY2456302 during the course of this study
• Any smoking of cigarettes or use of any nicotine containing products within the last month or at any time during the study
• History of blood donation in the last 3 months
• History of severe allergies or multiple adverse drug reactions
• Known hypersensitivity to LY2456302

Sponsors & Collaborators

• Andrew Krystal: lead
• Yale University: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

Related Publications (3)

• 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

• Zheng MQ, Nabulsi N, Kim SJ, Tomasi G, Lin SF, Mitch C, Quimby S, Barth V, Rash K, Masters J, Navarro A, Seest E, Morris ED, Carson RE, Huang Y. Synthesis and evaluation of 11C-LY2795050 as a kappa-opioid receptor antagonist radiotracer for PET imaging. J Nucl Med. 2013 Mar;54(3):455-63. doi: 10.2967/jnumed.112.109512. Epub 2013 Jan 25.

  PMID: 23353688 BACKGROUND

• Zheng MQ, Kim SJ, Holden D, Lin SF, Need A, Rash K, Barth V, Mitch C, Navarro A, Kapinos M, Maloney K, Ropchan J, Carson RE, Huang Y. An Improved Antagonist Radiotracer for the kappa-Opioid Receptor: Synthesis and Characterization of (11)C-LY2459989. J Nucl Med. 2014 Jul;55(7):1185-91. doi: 10.2967/jnumed.114.138701. Epub 2014 May 22.

  PMID: 24854795 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Anhedonia

Interventions

Aticaprant

Condition Hierarchy (Ancestors)

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

Study Officials

• Andrew D Krystal, MD, MS

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Psychiatry and Behavorial Sciences

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 18, 2014
• Study Start: October 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 28, 2015

Record last verified: 2015-05

Locations

US (1)