Sublingual Dexmedetomidine for Treating Opioid Withdrawal

NCT05712707 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 8325UG3DA056247-01
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 4

Brief Summary

A major challenge to seeking treatment for opioid use disorder (OUD) is the withdrawal symptoms associated with cessation of opioid use. The signs and symptoms of opioid withdrawal include irritability, anxiety, muscular and abdominal pains, chills, nausea, diarrhea, yawning, runny eyes and nose, sweating, sneezing, weakness, and insomnia. The current gold standard of treatment involves a gradual reduction of the opioid drug dosage (tapering). However, as all opioids have potential for abuse and require careful dosing due to side effects (e.g., respiratory depression), a non-opioid medication to facilitate withdrawal severity would be of great value. Commonly used non-opioid medications like lofexidine have concerning side effects including sedation and low blood pressure. BioXcel Therapeutics has developed BXCL501 (dexmedetomidine: sublingual film) to reduce symptoms associated with opioid withdrawal. Dexmedetomidine is currently used as an intravenous anesthetic for its anxiety-reducing, sedative, and analgesic properties. The current study will seek to compare the safety and efficacy of BXCL501 relative to lofexidine and placebo in subjects with OUD who are physically dependent on opioids. Throughout a 7-day inpatient withdrawal period (using a methadone taper) opioid-dependent participants will receive sublingual BXCL501, placebo, or lofexidine. In comparison to lofexidine, dexmedetomidine is expected to have a superior safety profile with limited adverse effects on blood pressure and heart rhythm. Three sites will participate in this study: NYSPI, Clinilabs, Inc., and Yale University. The NYSPI site is currently paused and has been paused since an institutional pause on human subjects research began in June 2023. The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.

Conditions

Opioid Use Disorder; Opioid Withdrawal

Outcome Measures

Primary Outcomes (1)

• Safety of BXCL501 versus Placebo and Lofexidine

  Establish the safety of BXCL501 relative to placebo and lofexidine in subjects with OUD who are physically dependent on opioids as measured by the frequency of adverse events.

  Study Days 1-7

Study Arms (4)

BXCL501 (180 micrograms)

EXPERIMENTAL

The current study is a randomized, double-blind, double-dummy inpatient study comparing BXCL501 (180 and 240 ug BID), lofexidine (as a positive control), and placebo.

Drug: BXCL501 (180 micrograms)

BXCL501 (240 micrograms)

EXPERIMENTAL

The current study is a randomized, double-blind, double-dummy inpatient study comparing BXCL501 (180 and 240 ug BID), lofexidine (as a positive control), and placebo.

Drug: BXCL501 (240 micrograms)

Lofexidine (Positive Control)

ACTIVE COMPARATOR

The current study is a randomized, double-blind, double-dummy inpatient study comparing BXCL501 (180 and 240 ug BID), lofexidine (as a positive control), and placebo.

Other: Lofexidine (Positive Control)

Placebo

PLACEBO COMPARATOR

The current study is a randomized, double-blind, double-dummy inpatient study comparing BXCL501 (180 and 240 ug BID), lofexidine (as a positive control), and placebo.

Other: Placebo

Interventions

BXCL501 (240 micrograms) DRUG

Throughout the 7-day inpatient study (Figure 1; Table 1), participants will receive sublingual BXCL501 or placebo twice daily and lofexidine or placebo 4 times daily using a double-blind, double-dummy design.

BXCL501 (240 micrograms)

Placebo OTHER

Throughout the 7-day inpatient study (Figure 1; Table 1), participants will receive sublingual BXCL501 or placebo twice daily and lofexidine or placebo 4 times daily using a double-blind, double-dummy design.

Placebo

BXCL501 (180 micrograms) DRUG

Throughout the 7-day inpatient study (Figure 1; Table 1), participants will receive sublingual BXCL501 or placebo twice daily and lofexidine or placebo 4 times daily using a double-blind, double-dummy design.

BXCL501 (180 micrograms)

Lofexidine (Positive Control) OTHER

Throughout the 7-day inpatient study (Figure 1; Table 1), participants will receive sublingual BXCL501 or placebo twice daily and lofexidine or placebo 4 times daily using a double-blind, double-dummy design.

Lofexidine (Positive Control)

Eligibility Criteria

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

You may qualify if:

• Capable of understanding and complying with the protocol.
• years of age or older but less than 60 years old.
• Has opioid use disorder moderate-to-severe (304.00) as per DSM-V, and physiological dependence on opioids.
• Females agree to use an acceptable method of contraception for the duration of the study.

You may not qualify if:

• Positive urine or serum pregnancy test at screening, after admission, planning to become pregnant during the course of the trial, or currently breast feeding.
• Clinically significant history of cardiac disease, including syncope, bradycardia, conduction abnormalities, orthostatic hypotension or blood pressure disorders. Heart rate and blood pressure at screening and baseline of \< 50 beats per minute or systolic blood pressure \<105, \>150 mmHg or diastolic BP \<70, \>90 mmHg.
• Clinically significant medical condition or observed abnormalities (including: physical examination, hypotension, laboratory evaluation, and/or urinalysis findings). Clinically significant abnormal ECG such as second- or third-degree heart block, uncontrolled arrhythmia, or QTc interval \> 450 msec for males, and \> 470 msec for females.
• Evidence of hepatic abnormalities, including: ascites, bilirubin \>10% above upper limit of normal and/or esophageal variceal disease, active hepatitis/aspartate aminotransferase, alanine aminotransferase \>3x the upper limit of normal.
• Any psychiatric disorder that would compromise ability to complete study requirements \[e.g. severe acute depression, active mania, or suicidality with specific plan and intent (assessed using the CSSRS)\].
• Not being able to provide a negative urine for methadone or buprenorphine at screening.
• Use of oral naltrexone for ≥7 consecutive days within 60 days prior to screening.
• Need for alcohol or benzodiazepine detoxification.
• Participation in a clinical trial of a pharmacological agent within 30 days prior to screening.
• Use of any concomitant medication at screening or anticipated/required use during the study period that the investigators feel may impact participant safety or interfere with the aims of the trial (e.g., daily licit or illicit benzodiazepine use).
• Any finding that, in the view of the principal investigator, would compromise the subject's ability to fulfill the protocol visit schedule or visit requirements.
• Investigator-site personnel or immediate family of investigator-site personnel.

Sponsors & Collaborators

• Yale University: collaborator
• New York State Psychiatric Institute: lead
• Clinilabs, Inc.: collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• CenExel HRI: collaborator
• BioXcel Therapeutics Inc: collaborator

Study Sites (4)

Yale University

New Haven, Connecticut, 06519, United States

Location

Clinilabs

Eatontown, New Jersey, 07724, United States

Location

CenExel HRI

Marlton, New Jersey, 08053, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (6)

• Antoine D, Huhn AS, Strain EC, Turner G, Jardot J, Hammond AS, Dunn KE. Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone. Am J Addict. 2021 Jan;30(1):83-87. doi: 10.1111/ajad.13069. Epub 2020 Jun 23.

  PMID: 32572978 BACKGROUND

• Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-1948. doi: 10.1016/S0140-6736(20)30852-7.

  PMID: 32563380 BACKGROUND

• Maze M, Segal IS, Bloor BC. Clonidine and other alpha2 adrenergic agonists: strategies for the rational use of these novel anesthetic agents. J Clin Anesth. 1988;1(2):146-57. doi: 10.1016/0952-8180(88)90034-7.

  PMID: 2908485 BACKGROUND

• Cedarbaum JM, Aghajanian GK. Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Eur J Pharmacol. 1977 Aug 15;44(4):375-85. doi: 10.1016/0014-2999(77)90312-0. No abstract available.

  PMID: 330174 BACKGROUND

• Fishman M, Tirado C, Alam D, Gullo K, Clinch T, Gorodetzky CW; CLEEN-SLATE Team. Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. J Addict Med. 2019 May/Jun;13(3):169-176. doi: 10.1097/ADM.0000000000000474.

  PMID: 30531234 BACKGROUND

• Shokri H, Ali I. A randomized control trial comparing prophylactic dexmedetomidine versus clonidine on rates and duration of delirium in older adult patients undergoing coronary artery bypass grafting. J Clin Anesth. 2020 May;61:109622. doi: 10.1016/j.jclinane.2019.09.016. Epub 2019 Oct 23.

  PMID: 31668468 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

lofexidine

Condition Hierarchy (Ancestors)

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

Study Officials

• Sandra Comer, Ph.D

  Columbia University / New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The current study is a randomized, double-blind, double-dummy inpatient study comparing BXCL501 (180 and 240 ug BID), lofexidine (as a positive control), and placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Psychiatrist

Model Details: Throughout the 7-day inpatient study, participants will receive sublingual BXCL501 or placebo twice daily and lofexidine or placebo 4 times daily using a double-blind, triple-dummy design. This study will utilize a methadone taper in order to ensure that opioid withdrawal severity is not so severe that it results in discharge immediately after enrollment (before a medication effect can be observed). Throughout the 7-day inpatient study, participants will receive: Methadone QID at 9am, 2pm, 7pm, 11pm. Total daily methadone doses: Day 1= 30mg, Day 2= 25mg, Day 3= 20mg, Day 4= 15 mg, Day 5= 10mg, Day 6= 5mg, Day 7= 0mg. On each day a PRN methadone dose of 5mg x 2, will also be available (total daily dose will not exceed 40mg).

Study Record Dates

• First Submitted: January 24, 2023
• First Posted: February 3, 2023
• Study Start: February 28, 2023
• Primary Completion: June 30, 2025
• Study Completion (Estimated): August 31, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (4)