Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder

ABSTRACT

Background: Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal.

Objectives: To evaluate the feasibility, safety, and tolerability of lofexidine for facilitating induction onto ER-NTX in the management of OUD.

Methods: In an open-label, uncontrolled, 10-week outpatient clinical trial, 20 adults (four women) with OUD were treated with a fixed-flexible dosing strategy (maximum 0.54 mg 4×/daily) of lofexidine for up to 10 days to manage opioid withdrawal prior to receiving ER-NTX. The COVID-19 pandemic resulted in a modification of the study methods after enrolling 10 participants who attended all visits in person. The second group of 10 participants attended most induction period visits remotely.

Results: Overall, 10 of the 20 participants (50%) achieved the primary outcome by receiving the first ER-NTX injection. Rates of induction success did not differ by the presence of fentanyl or remote visit attendance, although the small sample size provided limited statistical power. Six out of 20 participants (30%) initiated on lofexidine required dose adjustments. There were no study-related serious adverse events.

Conclusions: This study provides preliminary evidence supporting the feasibility of inducting individuals with OUD onto ER-NTX using lofexidine.

KEYWORDS:

• Lofexidine
• pharmacotherapy
• naltrexone
• opioid use disorder

Acknowledgments

US WorldMeds had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Dr. Mariani had full access to all the data of the study and takes full responsibility for the integrity of the data and for the accuracy of the data analysis. We would like to thank the staff of the Substance Treatment and Research Service (STARS) of the Columbia University Irving Medical Center/New York State Psychiatric Institute for their efforts in conducting.

Disclosure statement

Dr. Mariani has served as a consultant and speaker for Indivior and has current grant funding from the NIAAA. Dr. Levin receives grant support from the NIDA, NCATS, SAMHSA and US World Meds and has been an unpaid member of a Scientific Advisory Board for Alkermes, Novartis and US WorldMeds. Drs. Pavlicova, Brezing and Naqvi reported no biomedical financial interests or potential conflicts of interest. Also, Mr. Basaraba, Mr. Alschuler, Ms. Mahony, and Mr. Brooks reported no biomedical financial interests or potential conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Trial registration

clinicaltrials.gov identifier: NCT04056182.

Additional information

Funding

Funding for this research was provided by US WorldMeds (Levin).