Phase I Functional Magnetic Resonance Imaging (fMRI) Pharmacodynamic Studies of Compounds for Opioid Use Disorder and Cocaine Use Disorder

NCT03143543 | Terminated Phase 1 FDA Drug

• 2 other identifiers: HM200033295U54DA038999-04
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of Project 2 is to execute phase I functional magnetic resonance imaging (fMRI) studies to assess the effects of lorcaserin on brain target engagement (measured by fMRI brain activation and neural connectivity) in cocaine use disorder (CocUD) subjects and/or opioid use disorder.

Conditions

Cocaine-Related Disorders; Opioid-Related Disorders

Keywords

cocaine disorder; opioid disorder; lorcaserin; MRI; fMRI

Outcome Measures

Primary Outcomes (1)

• Target engagement by lorcaserin

  To determine target engagement by lorcaserin in a cocaine-Stroop and/or opioid-Stroop cue-reactivity fMRI task in cocaine use disorder (CocUD) and/or Opioid Use Disorder Subjects

  Seven Days

Study Arms (4)

Group A Lorcaserin (10mg)

EXPERIMENTAL

10 mg lorcaserin orally for 7 days

Drug: Group A Lorcaserin (10mg)

Group B Parallel Placebo

PLACEBO COMPARATOR

Placebo orally for 7 days vs Group A

Other: Group B Parallel Placebo

Group A2 Lorcaserin (20 mg)

EXPERIMENTAL

20 mg lorcaserin orally for 7 days

Drug: Group A2 Lorcaserin (20 mg)

Group B2Parallel Placebo

PLACEBO COMPARATOR

Placebo orally for 7 days vs Group A2

Other: Group B2 Parallel Placebo

Interventions

Group A Lorcaserin (10mg) DRUG

10 mg lorcaserin orally for 7 days

Also known as: Belviq

Group A Lorcaserin (10mg)

Group A2 Lorcaserin (20 mg) DRUG

20 mg lorcaserin orally for 7 days

Also known as: Belviq

Group A2 Lorcaserin (20 mg)

Group B Parallel Placebo OTHER

Oral placebo vs 10 mg lorcaserin

Group B Parallel Placebo

Group B2 Parallel Placebo OTHER

Oral placebo vs 20 mg lorcaserin

Group B2Parallel Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females treatment-seeking cocaine and/or opioid users between 18 and 55 years of age
• Understand the study procedures and provide written informed consent
• Must be in residential treatment for substance use disorder
• Meet current DSM-5 criteria for Cocaine Use Disorder with moderate or severe severity, and current DSM-IV diagnosis of Cocaine Dependence or Abuse, and/or current DSM-5 criteria for Opioid Use Disorder with moderate or severe severity, and/or current DSM-IV diagnosis of Opioid Dpendence or Abuse.
• Have been abstinent from cocaine and/or opioid use for at least 1 week
• Have vital signs as follows: resting pulse between 55 and 95 bpm, blood pressures between 90-139 mm Hg systolic and 50-89 mm Hg diastolic
• Have hematology and chemistry laboratory tests that are within normal limits, except that liver function tests must be less than twice the upper limit of normal and judged by the study physician to be clinically insignificant.
• Have a normal baseline ECG as shown by normal sinus rhythm with the exception of sinus arrhythmia or mild sinus bradycardia (heart rate 50-59 beats per minute), and with normal conduction (including normal QTcF) with the exception of early repolarization judged to be clinically insignificant by both the study physician and the study cardiologist.
• For adults who ar 20 years old or older, have a Body Mass Index (BMI) that is 18.5 or greater according to the CDC Calculator for Adults.. For adolescents who are 18 or 19 years old, BMI that is fifth percentile or greater according to the CDC Calculator for Children and Teens.
• Have no contraindications for study participation as determined by history and physical examination
• Be able to demonstrate an understanding of study procedures and follow instructions including behavioral laboratory and fMRI testing
• No pregnant or nursing women will be permitted in the study, and women must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device with spermicide, or condoms). Men will be advised to use condoms. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and at the end of study participation.

You may not qualify if:

• Have concurrent DSM-IV diagnosis of any psychoactive substance use dependence other than cocaine, nicotine, marijuana, or opioid dependence.
• Have a DSM-5 axis I psychiatric disorder, other than substance use disorder, including by not limited to Bipolar Disorder, Major Depressive Disorder, ADHD, or Schizophrenia, or a neurological disorder requiring ongoing treatment and/or making study participation unsafe.
• Subjects with evidence or history of any clinically significant medical disorder including cardiovascular, pulmonary, CNS, hepatic, or renal, except that controlled hypertension, controlled hypothyroidism, and cancer in remission will not be excluded.
• Subjects who have Type 1 or Type 2 diabetes mellitus, since weight loss may increase the risk of hypoglycemia in patients with Type 2 diabetes mellitus treated with insulin secretagogues (eg., sulfonylureas), and lorcaserin has not been studied in combination with insulin.
• Subjects with an abnormal QTcF on ECG
• Have a history of seizures (excluding childhood febrile seizures), or loss of consciousness for more than 20 minutes
• Have significant current suicidal or homicidal ideation or a suicide attempt within the past 6 months
• Be HIV positive by self-report or history
• Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and at the end of study participation
• Have an other illness or condition, which in the opinion of the PI would preclude safe and/or successful completion of the study.
• Be using any medications or drugs that can affect the central nervous system other than cocaine, marijuana, alcohol, caffeine, and nicotine.
• Be using any medication (including over-the-counter medication or food suplements) that may interact adversely with lorcaserin, including other serotonergic drugs, including SNRIs and SSRIs, triptans, drugs that impair metabolism of serotonin (including MAOIs), dietary supplements such as St. John's wort and tryptophan, tramadol, or antipsychotics or other dopamine antagonists.. See Lorcaserin Drug Interactions table (attached) for detailed list of these medications.
• Prior to starting study medication, and prior to each MRI scanning session, have positive breath alcohol level, or have a positive urine drug screen for any drug of abuse other than marijuana.
• Have metal fragments or other bodily metal (e.g., pacemaker), or significant claustrophobia that would put the subjects at risk for MRI scanning.
• Subjects who are allergic to lorcaserin

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders; Opioid-Related Disorders

Interventions

lorcaserin

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Narcotic-Related Disorders

Study Officials

• James Bjork, PhD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Starting lorcaserin dosage of 10 mg per day for 7 days in one arm, versus placebo for 7 days in parallel arm. An interim analysis will take place after 15 subjects have completed at each arm. Based on the interim analysis, if there is no significant effect and no trend towards significance for the lower dose of lorcaserin in the primary regions of interest for fMRI task, and no significant accumulation of adverse effects, testing will stop for the lower dose of lorcaserin, and testing will begin for the higher dose, which is the FDA approved usual dose for lorcaserin (20 mg per day, given as 10 mg twice per day). The higher dose of lorcaserin will be tested in a two group parallel arm design, initially with 15 subjects in lorcaserin arm and 15 subjects in the parallel placebo arm. Another interim analysis will take place after 15 subjects have completed at each arm in the higher dose lorcaserin study.

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: May 8, 2017
• Study Start: July 1, 2015
• Primary Completion: December 6, 2019
• Study Completion: December 6, 2019
• Last Updated: April 27, 2020

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)