Lorcaserin in Combination With XR-Naltrexone for Relapse Prevention in Opioid Use Disorder

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT03169816
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Actual Duration (Months): 27.2
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

This study proposes to recruit patients with Opioid Use Disorder (OUD) seeking treatment into our program of outpatient detoxification and naltrexone induction followed by a relapse-prevention treatment with Extended release-naltrexone (XR-NTX) . Eligible participants will be randomly assigned to adjunctive treatment with lorcaserin (N = 40), or placebo (N = 20) with weekly therapy.

Condition or Disease	Intervention/Treatment	Phase
Opioid-use Disorder	Drug: Lorcaserin; Drug: Placebo	Phase 2/Phase 3

Detailed Description

The study proposes to recruit patients with Opioid Use Disorder (OUD) seeking treatment into our program of outpatient detoxification and naltrexone induction followed by a relapse-prevention treatment with Extended release-naltrexone (XR-NTX) . Eligible participants will be randomly assigned to adjunctive treatment with lorcaserin (N = 40), or placebo (N = 20) with weekly therapy. Lorcaserin or placebo 10 mg bid will be started on Day 1 of the study to address acute withdrawal, then maintained over the next 5 weeks, and stopped after the second XR-naltrexone is administered. Patients will be seen twice weekly for monitoring and offered two injections of naltrexone; at the end of oral naltrexone induction (end of week 1) and four weeks later (week 5). The primary outcome measures will be the proportion of patients successfully inducted onto XR-naltrexone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Lorcaserin in Combination With XR-Naltrexone for Relapse Prevention in Opioid Use Disorder
• Actual Study Start Date: May 25, 2017
• Actual Primary Completion Date: Aug 30, 2019
• Actual Study Completion Date: Aug 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lorcaserin 10 mg capsule taken twice daily of lorcaserin	Drug: Lorcaserin; Lorcaserin 10mg, twice daily
Placebo Comparator: Placebo a placebo comparator capsule taken twice daily	Drug: Placebo; Matched placebo for lorcaserin condition dosed twice daily

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Successfully Inducted to Receive Naltrexone Injection [Study week 1]

   proportion of individuals who were successfully inducted and received the first XR-naltrexone injection

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 1. Individuals between the ages of 18-60

1. Meets DSM-5 criteria of current opioid use disorder present for at least six months, supported by a positive urine for opioids

2. Seeking treatment for opioid use disorder

3. Capable of giving informed consent and complying with study procedures

4. Not underweight; defined as BMI≥18.5

Exclusion Criteria:

1. Lifetime history of DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder

2. Current DSM-5 criteria for any other psychiatric disorder that in the investigator's judgment is unstable, would be disrupted by the study medication, or is likely to require pharmacotherapy or psychotherapy during the study period. Concurrent treatment with other psychotropic medication is exclusionary.

3. Individuals who meet DSM-5 criteria for any substance use disorders - severe, other than opioid and nicotine use disorder. Physiological dependence on alcohol or sedative-hypnotics is exclusionary.

4. A recent history of binge-use of alcohol or sedative-hypnotics (using large amounts in a short time to severe intoxication or blackouts).

5. Pregnancy, lactation, or failure to use adequate contraceptive method in female patients who are currently engaging in sexual activity with men.

6. Unstable medical conditions, such as AIDS, cancer, uncontrolled hypertension (blood pressure > 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease.

7. Legally mandated to participate in a substance use disorder treatment program.

8. Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide

9. Currently meets DSM-5 diagnosis for an eating disorder with low body weight (BMI <20)

10. History of accidental opioid overdose in the last three years or any other significant history of overdose following detoxification within past 10 years defined as an episode of opioid-induced unconsciousness, whether or not medical treatment was sought or received.

11. Elevated liver function tests (AST and ALT > 3 times the upper limit of normal) or impaired renal function (GFR<60 ml/min)

12. Known history of allergy, intolerance, or hypersensitivity to lorcaserin, naltrexone or any other study medications

13. Concurrent use of migraine medications containing ergotamine (Cafergot, Ergomar) or dihydroergotamine (Migranal), 5HT2B receptor agonists like cabergoline, or medications metabolized by CYP2D6 (thioridazine, tamoxifen, metoprolol, aripiprazole, codeine)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Substance Treatment and Research Service (STARS), Columbia University	New York	New York	United States	10019

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

• Principal Investigator: Frances R Levin, MD, NYSPI

Study Documents (Full-Text)

• Study Protocol - May 25, 2017
• Statistical Analysis Plan - May 25, 2017

More Information

Publications

None provided.

• Responsible Party: Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT03169816
• Other Study ID Numbers: 7501
• First Posted: May 30, 2017
• Last Update Posted: Oct 5, 2020
• Last Verified: Sep 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
• Additional relevant MeSH terms: Opioid-Related Disorders; Substance-Related Disorders

Study Results

Participant Flow

Pre-assignment Detail	60 patients were enrolled in the trial but of these 49 patients were randomized to one of the treatment arms.

Arm/Group Title	Lorcaserin	Placebo
Arm/Group Description	10 mg capsule taken twice daily of lorcaserin Lorcaserin: Lorcaserin 10mg, twice daily	a placebo comparator capsule taken twice daily Placebo: Matched placebo for lorcaserin condition dosed twice daily
Period Title: Overall Study
STARTED	33	16
COMPLETED	6	3
NOT COMPLETED	27	13

Baseline Characteristics

Arm/Group Title	Lorcaserin	Placebo	Total
Arm/Group Description	10 mg capsule taken twice daily of lorcaserin Lorcaserin: Lorcaserin 10mg, twice daily	a placebo comparator capsule taken twice daily Placebo: Matched placebo for lorcaserin condition dosed twice daily	Total of all reporting groups
Overall Participants	33	16	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.8 (9.9)	39.5 (12.6)	37.0 (10.9)
Sex: Female, Male (Count of Participants)
Female	8 24.2%	3 18.8%	11 22.4%
Male	25 75.8%	13 81.3%	38 77.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 21.2%	2 12.5%	9 18.4%
Not Hispanic or Latino	26 78.8%	14 87.5%	40 81.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 6.3%	1 2%
Asian	0 0%	1 6.3%	1 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 15.2%	4 25%	9 18.4%
White	22 66.7%	10 62.5%	32 65.3%
More than one race	3 9.1%	0 0%	3 6.1%
Unknown or Not Reported	3 9.1%	0 0%	3 6.1%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Successfully Inducted to Receive Naltrexone Injection
Description	proportion of individuals who were successfully inducted and received the first XR-naltrexone injection
Time Frame	Study week 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin	Placebo
Arm/Group Description	10 mg capsule taken twice daily of lorcaserin Lorcaserin: Lorcaserin 10mg, twice daily	a placebo comparator capsule taken twice daily Placebo: Matched placebo for lorcaserin condition dosed twice daily
Measure Participants	33	16
Count of Participants [Participants]	12 36.4%	7 43.8%

Adverse Events

Time Frame	During the 8 weeks of the trial or length of participant's participation.
Arm/Group Title	Lorcaserin		Placebo
Arm/Group Description	10 mg capsule taken twice daily of lorcaserin Lorcaserin: Lorcaserin 10mg, twice daily		a placebo comparator capsule taken twice daily Placebo: Matched placebo for lorcaserin condition dosed twice daily
All Cause Mortality
	Lorcaserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/16 (0%)
Serious Adverse Events
	Lorcaserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/33 (6.1%)		0/16 (0%)
General disorders
Inpatient rehabilitation	2/33 (6.1%)	2	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Lorcaserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/33 (42.4%)		7/16 (43.8%)
Gastrointestinal disorders
GI Upset	4/33 (12.1%)	4	1/16 (6.3%)	1
Vomiting	3/33 (9.1%)	3	1/16 (6.3%)	1
Diarrhea	1/33 (3%)	1	1/16 (6.3%)	1
Hot flashes	2/33 (6.1%)	2	0/16 (0%)	0
Constipation	0/33 (0%)	0	1/16 (6.3%)	1
Nausea	0/33 (0%)	0	1/16 (6.3%)	1
GI Ulcer	0/33 (0%)	0	1/16 (6.3%)	1
General disorders
insomnia	3/33 (9.1%)	3	3/16 (18.8%)	3
Anorexia	2/33 (6.1%)	2	2/16 (12.5%)	2
Chills	2/33 (6.1%)	2	0/16 (0%)	0
Precipitated Withdrawal	1/33 (3%)	1	1/16 (6.3%)	1
Blackout	0/33 (0%)	0	1/16 (6.3%)	1
Dehydration	1/33 (3%)	1	0/16 (0%)	0
Fatigue	0/33 (0%)	0	1/16 (6.3%)	1
Fainting	1/33 (3%)	1	0/16 (0%)	0
Gout	1/33 (3%)	1	0/16 (0%)	0
Headache	1/33 (3%)	1	0/16 (0%)	0
Head Sensation	1/33 (3%)	1	0/16 (0%)	0
Irritable	1/33 (3%)	1	0/16 (0%)	0
Leg Cramps	1/33 (3%)	1	0/16 (0%)	0
Loss of Libido	1/33 (3%)	1	0/16 (0%)	0
Sexual Dysfunction	1/33 (3%)	1	0/16 (0%)	0
Musculoskeletal and connective tissue disorders
Bachache	1/33 (3%)	1	0/16 (0%)	0
Muscle Aches	0/33 (0%)	0	1/16 (6.3%)	1
Psychiatric disorders
Anxiety	3/33 (9.1%)	3	0/16 (0%)	0
Suicidal Ideation	1/33 (3%)	1	0/16 (0%)	0

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.