Impact of Lofexidine on Stress, Craving and Opioid Use

NCT03718065 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: Pro000813812U54DA016511-16
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with opioid use disorder who are stabilized on buprenorphine or methadone will be randomly assigned to receive placebo or lofexidine for 5 weeks. At the end of five weeks, they will complete a human laboratory stress task and scripted opioid imagery task. Throughout the study a CREMA app (Cue Reactivity Ecological Momentary Assessment) will be used to monitor stress, craving and use in the natural environment.

Conditions

Opioid-use Disorder; Opiate Dependence

Outcome Measures

Primary Outcomes (2)

• Drug Cue+ Stressor Induced Craving

  Participants will rate craving on a 0 to 7 Likert scale with 0 indicate "Strongly disagree" that they crave and 7 indicating "strongly agree" that they crave so that higher scores indicate more craving.

  Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline

• Drug Cue+ Stressor Induced Stress Response

  Participants will rate stress on a 0 to 4 Likert scale with 0 indicate "not at all" and 4 indicating "extremely" so that higher scores indicate a more robust stress response.

  Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline

Study Arms (4)

Lofexidine Men

EXPERIMENTAL

Men will receive lofexidine (Lucemyra) for 5 weeks. Titration schedule is as follows: 0.36 mg on the first two evenings, 0.36 mg in the morning and evening on days 3 and 4; 0.36 mg in the morning, afternoon, and at bedtime on days 5 and 6; 0.36 mg in the morning and afternoon and 0.72 mg at bedtime on days 7 and 8; 0.36 mg in the morning and 0.72 mg in the afternoon and at bedtime on days 9 and 10, and 0.72 mg in the morning, afternoon and at bedtime on Day 11 and throughout the rest of the study.

Drug: Lofexidine

Lofexidine Women

EXPERIMENTAL

Women will receive lofexidine (Lucemyra) for 5 weeks. Titration schedule is as follows: 0.36 mg on the first two evenings, 0.36 mg in the morning and evening on days 3 and 4; 0.36 mg in the morning, afternoon, and at bedtime on days 5 and 6; 0.36 mg in the morning and afternoon and 0.72 mg at bedtime on days 7 and 8; 0.36 mg in the morning and 0.72 mg in the afternoon and at bedtime on days 9 and 10, and 0.72 mg in the morning, afternoon and at bedtime on Day 11 and throughout the rest of the study.

Drug: Lofexidine

Placebo Men

PLACEBO COMPARATOR

Men will receive matching placebo for five weeks.

Drug: Placebo

Placebo Women

PLACEBO COMPARATOR

Women will receive matching placebo for five weeks.

Drug: Placebo

Interventions

Lofexidine DRUG

Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure, but more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist.

Also known as: Lucemyra

Lofexidine Men; Lofexidine Women

Placebo DRUG

Placebo comparator.

Placebo Men; Placebo Women

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
• Meet DSM-5 criteria for opioid use disorder (within the past three months). While individuals may also meet criteria for mild use disorders of other substances, they must identify opioids as their primary substance of abuse and must not meet criteria for any other moderate or severe substance use disorder (except tobacco, caffeine, or marijuana) within the last 60 days.
• On a stable dose of daily buprenorphine or methadone for at least 2 weeks.
• Age 18-65.
• Women of childbearing potential must agree to use an effective means of birth control.
• Consent to remain abstinent from opioids during the 1-week baseline assessment period.
• Must consent to random assignment.

You may not qualify if:

• Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
• Evidence or history of major medical illnesses, including liver diseases, abnormal vaginal bleeding, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, insulin-dependent diabetes, history of stroke or other medical conditions that the investigator deems as contraindicated for the individual to be in the study.
• History of or current psychotic disorder or bipolar I affective disorder.
• Current suicidal or homicidal ideation/risk.
• Taking medications known to act on adrenergic systems (B-blockers; alpha agonists or antagonists)
• Hypotensive individuals with a sitting blood pressure of \< 90/50
• QTc interval of \>440 in males and \> 460 in females as the combination of lofexidine plus buprenorphine may increase the QTc interval.
• Known allergy to lofexidine
• Unable to comply with study procedures or pose threat to study staff.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Related Publications (1)

• Guille C, King C, Ramakrishnan V, Baker N, Cortese B, Nunn L, Rogers T, McRae-Clark A, Brady K. The impact of lofexidine on stress-related opioid craving and relapse: Design and methodology of a randomized clinical trial. Contemp Clin Trials. 2021 Dec;111:106616. doi: 10.1016/j.cct.2021.106616. Epub 2021 Nov 2.

  PMID: 34737091 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

lofexidine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Constance Guille
• Organization: Medical University of South Carolina

guille@musc.edu

843-792-6489

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 24, 2018
• Study Start: June 26, 2019
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2024
• Last Updated: February 7, 2025
• Results First Posted: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)