Drug Interaction and Subjective Effects of Compounds for Opioid Use Disorder

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03143855
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 26.1
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The overall goal of this project is to develop initial human data on effects of novel compounds on safety (interactions with oxycodone) and efficacy (subjective response to oxycodone) in non-treatment seeking opioid use disorder subjects. The compound to be studied will be the 5-HT2CR agonist lorcaserin. There are no known or reported adverse interactions between lorcaserin and oxycodone or other opioids.

Condition or Disease	Intervention/Treatment	Phase
Opioid Abuse; Opioid Dependence; Opioid-Related Disorders; Opioid Use	Drug: Lorcaserin; Drug: Placebo	Phase 1

Detailed Description

Lorcaserin is a serotonin (5-HT) 2C receptor agonist (Trade Name Belviq) approved for treatment of obesity. The study teams's preclinical research collaborators and others have shown that lorcaserin and other 5-HT2CR agonists have been shown to reduce drugs of abuse self-administration and cue reactivity in rodents including cocaine and nicotine. Recently, this data has been expanded to opioids. Rats trained to self-administer oxycodone showed a significant reduction in self-administration and oxycodone cue induced lever presses after lorcaserin administration.

This is a single center, double-blind, placebo-controlled, randomized, 1b/2a study. 18 subjects are planned. The following treatment regimens will be used:

Lorcaserin will be administered at a dose of 10mg twice daily. Placebo or Comparator - identical placebo capsules administered at the same time as lorcaserin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase I Drug Interaction and Subjective Effects of Compounds for Opioid Use Disorder
• Actual Study Start Date: Jan 30, 2017
• Actual Primary Completion Date: Apr 5, 2019
• Actual Study Completion Date: Apr 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lorcaserin	Drug: Lorcaserin; Lorcaserin will be administered at a dose of 10 mg twice daily for 5 days
Placebo Comparator: Control Group	Drug: Placebo; Placebo will be administered twice daily for for 5 days

Outcome Measures

Primary Outcome Measures

1. Change in Subjective Response to Oxycodone Measured With 100 Millimeter Visual Analog Scale [Baseline to day 5]

   Drug liking is measured on a 100 millimeter visual analog rating with one end of the line representing a score of 0 for "not at all" and the other end being a score of 100 or extremely. Participants complete the rating 45 minutes after a 20 mg dose of oxycodone at baseline and after after 5 days of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

In order to participate in this study, subjects must:

1. Males and females between 18 and 70 years-of-age.

2. Understand the study procedures and provide written informed consent.

3. Meet current DSM-5 criteria for opioid use disorder, at least moderate severity, but are not seeking treatment.

4. Have at least one positive urine drug screen for opioids during screening to document opioid use.

5. Have no clinically significant abnormalities in the judgment of the study physician in hematology and chemistry laboratory tests including liver function tests.

6. Have no contraindications for study participation as determined by medical history and physical examination.

7. Be able to demonstrate an understanding of study procedures and follow instructions including behavioral laboratory testing.

8. 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.

Exclusion Criteria:

In order to participate in the study, subjects must not:

1. Meet current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, marijuana, cocaine or nicotine. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary (SCID).

2. Have a current DSM-5 axis I psychiatric disorder other than substance use disorder including but not limited to Bipolar Disorder, Major Depressive Disorder, ADHD, or Schizophrenia or a neurological disorder requiring ongoing treatment and/or making study participation unsafe.

3. Have any previous medically adverse reaction to oxycodone or other opioids or lorcaserin.

4. Have any untreated clinically significant medical disorder including cardiovascular, pulmonary, CNS, hepatic, or renal disorder.

5. Have a history of seizures (excluding childhood febrile seizures), or loss of consciousness from traumatic injury for more than 30 minutes.

6. Have significant current suicidal or homicidal ideation or a history of suicide attempt within the past 6 months.

7. Have conditions of probation or parole requiring reports of drug use to officers of the court.

8. Have impending incarceration.

9. Have a positive HIV test by self-report or history.

10. Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females must provide negative pregnancy urine tests at screening, and daily after hospital admission.

11. Have any other illness, or condition, which in the opinion of the PI would preclude safe and/or successful completion of the study.

12. Have taken any investigational drug within 90 days prior to baseline.

13. Have an allergy to lorcaserin or oxycodone.

14. Have taken or are currently taking drugs that are know to inhibit cytochrome P450, CYP3A or CYP2D6.

15. ECG with QTc > 440ms.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Frederick G Moeller, MD, Virginia Commonwealth University

Study Documents (Full-Text)

• Informed Consent Form - Mar 7, 2018
• Study Protocol and Statistical Analysis Plan - Feb 12, 2018

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT03143855
• Other Study ID Numbers: HM20008062; U54DA038999
• First Posted: May 8, 2017
• Last Update Posted: Nov 12, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Virginia Commonwealth University: oxycodone; lorcaserin; Belviq
• Additional relevant MeSH terms: Opioid-Related Disorders

Study Results

Participant Flow

Recruitment Details	32 participants signed the consent form however 5 participants were no shows for the initial visit at which ranndomization occurred.

Arm/Group Title	Lorcaserin	Control Group
Arm/Group Description	Lorcaserin: Lorcaserin will be administered at a dose of 10 mg twice daily for 5 days	Placebo: Placebo will be administered twice daily for for 5 days
Period Title: Overall Study
STARTED	17	10
COMPLETED	12	6
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Lorcaserin	Control Group	Total
Arm/Group Description	Lorcaserin: Lorcaserin will be administered at a dose of 10 mg twice daily for 5 days	Placebo: Placebo will be administered twice daily for for 5 days	Total of all reporting groups
Overall Participants	12	6	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (10.2)	46 (8.8)	48 (0.5)
Sex: Female, Male (Count of Participants)
Female	1 8.3%	2 33.3%	3 16.7%
Male	11 91.7%	4 66.7%	15 83.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	10 83.3%	5 83.3%	15 83.3%
White	2 16.7%	1 16.7%	3 16.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	6 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Change in Subjective Response to Oxycodone Measured With 100 Millimeter Visual Analog Scale
Description	Drug liking is measured on a 100 millimeter visual analog rating with one end of the line representing a score of 0 for "not at all" and the other end being a score of 100 or extremely. Participants complete the rating 45 minutes after a 20 mg dose of oxycodone at baseline and after after 5 days of treatment.
Time Frame	Baseline to day 5

Outcome Measure Data

Analysis Population Description

Males and Females between ages 18 and 70 who meet criteria for opioid use disorder, at least moderate severity, but are not seeking treatment. Subjects diagnosed with a current psychiatric disorder or mental disorder including cardiovascular, pulmonary, CNS, hepatic or renal disorder are excluded from participation.

Arm/Group Title	Lorcaserin	Control Group
Arm/Group Description	Lorcaserin: Lorcaserin will be administered at a dose of 10 mg twice daily for 5 days	Placebo: Placebo will be administered twice daily for for 5 days
Measure Participants	11	6
Mean (Standard Deviation) [units on a scale]	-13.81 (31.7)	-9.67 (32.6)

Adverse Events

Time Frame	5 days
Arm/Group Title	Lorcaserin		Control Group
Arm/Group Description	Lorcaserin: Lorcaserin will be administered at a dose of 10 mg twice daily for 5 days		Placebo: Placebo will be administered twice daily for for 5 days
All Cause Mortality
	Lorcaserin		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)
Serious Adverse Events
	Lorcaserin		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Lorcaserin		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/6 (16.7%)
Psychiatric disorders
Emesis	0/12 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.