Sublingual Dexmedetomidine for Opioid Withdrawal

Recruiting at 3 trial locations

Overseen By Howard Hassman, D.O., AOBFP

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: New York State Psychiatric Institute

Must be taking: Opioids

Must not be taking: Naltrexone, Benzodiazepines

Disqualifiers: Pregnancy, Cardiac disease, Psychiatric disorder, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

160 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that the use of any medication that may impact safety or interfere with the trial is not allowed, so you should discuss your current medications with the trial investigators.

What data supports the effectiveness of the drug dexmedetomidine for treating opioid withdrawal?

Research shows that sublingual dexmedetomidine (BXCL501) can reduce opioid withdrawal symptoms, with higher doses leading to significant improvements in withdrawal scores. Additionally, dexmedetomidine has been effective in managing withdrawal symptoms in both adults and infants in various settings, suggesting its potential usefulness for opioid withdrawal. ^{1 2 3 4 5}

Is sublingual dexmedetomidine safe for treating opioid withdrawal?

Sublingual dexmedetomidine has been studied for safety in treating opioid withdrawal, with some participants experiencing mild to moderate side effects like low blood pressure and drowsiness. In rare cases, severe side effects like low heart rate and low blood pressure occurred, but overall, it was generally well-tolerated. ^{1 2 4 6 7}

How is the drug dexmedetomidine unique in treating opioid withdrawal?

Dexmedetomidine is unique because it is administered sublingually (under the tongue) and works by targeting alpha-2 adrenergic receptors, which may reduce opioid withdrawal symptoms with fewer heart-related side effects compared to other treatments. ^{1 3 4 5 8}

Research Team

Sandra Comer, Ph.D

Principal Investigator

Columbia University / New York State Psychiatric Institute

Eligibility Criteria

This trial is for adults aged 18-60 with moderate-to-severe opioid use disorder who are physically dependent on opioids. Participants must understand the study and agree to contraception if applicable. Exclusions include methadone or buprenorphine in urine, pregnancy, significant medical conditions, abnormal ECGs, liver issues, recent naltrexone use, certain medication uses that affect safety or trial outcomes, psychiatric disorders affecting study compliance, alcohol/benzodiazepine detox need, recent other clinical trial participation and specific cardiac history.

Inclusion Criteria

I understand and can follow the study's requirements.

I am between 18 and 60 years old.

I agree to use birth control during the study.

Exclusion Criteria

You have a severe psychiatric disorder, such as depression or mania, that may make it difficult for you to complete the study requirements.

You have participated in another clinical trial with a drug in the last 30 days before screening.

I have a history of significant heart issues or my heart rate/blood pressure doesn't meet the specified range.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sublingual BXCL501, placebo, or lofexidine during a 7-day inpatient withdrawal period using a methadone taper

1 week

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexmedetomidine

Trial Overview The trial tests BXCL501 (dexmedetomidine sublingual film) against lofexidine and a placebo to see which better reduces opioid withdrawal symptoms without severe side effects like low blood pressure. Over seven days inpatient treatment at three sites will compare their safety and efficacy in individuals withdrawing from opioids.

Participant Groups

Group I: BXCL501 (240 micrograms) Experimental Treatment 1 Intervention

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.

Group II: BXCL501 (180 micrograms) Experimental Treatment 1 Intervention

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.

Group III: Lofexidine (Positive Control) Active Control 1 Intervention

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.

Group IV: Placebo Placebo Group 1 Intervention

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.

Dexmedetomidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in United States as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Canada as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Japan as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

CenExel HRI

Collaborator

Trials

1

Recruited

160+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

BioXcel Therapeutics Inc

Industry Sponsor

Trials

20

Recruited

2,400+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Clinilabs, Inc.

Collaborator

Trials

9

Recruited

650+

Findings from Research

Dexmedetomidine, an alpha 2 adrenergic agonist, is primarily approved for sedation during mechanical ventilation in adults, but it may also be effective in managing substance withdrawal symptoms in intensive care settings.

In a small case series involving 3 patients after cardiothoracic surgery, dexmedetomidine was used to successfully control withdrawal behavior, suggesting its potential as a treatment option for withdrawal in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine in the treatment of withdrawal syndromes in cardiothoracic surgery patients. Baddigam, K., Russo, P., Russo, J., et al.[2013]

In a study of 73 patients undergoing laparoscopic bariatric surgery, those who received dexmedetomidine experienced a significant reduction in narcotic use (66 mg vs 130 mg of morphine equivalents) and were more likely to meet discharge criteria on the first postoperative day (61% vs 26%).

Dexmedetomidine was found to be safe and effective in minimizing narcotic requirements and potentially reducing hospital stay duration, which is particularly beneficial for patients with a high risk of respiratory complications, such as those with obstructive sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of perioperative dexmedetomidine infusion on postoperative narcotic use and duration of stay after laparoscopic bariatric surgery. Dholakia, C., Beverstein, G., Garren, M., et al.[2018]

In a study of seven infants aged 3 to 24 months experiencing opioid withdrawal after sedation during mechanical ventilation, dexmedetomidine effectively controlled withdrawal symptoms, with Finnegan scores dropping to ≤7 after treatment.

No adverse hemodynamic or respiratory effects were observed, suggesting that dexmedetomidine is a safe and viable option for managing opioid withdrawal in pediatric intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine to treat opioid withdrawal in infants following prolonged sedation in the pediatric ICU. Tobias, JD.[2019]

In a study of 225 participants with opioid dependence, sublingual dexmedetomidine (BXCL501) showed preliminary efficacy in reducing withdrawal symptoms, particularly at higher doses (120, 180, and 240 μg), as indicated by significant reductions in Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS) scores.

While higher doses of BXCL501 were associated with mild to moderate adverse effects like hypotension and somnolence, the overall safety profile was acceptable, supporting further development of BXCL501 for opioid withdrawal management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual dexmedetomidine (BXCL501) reduces opioid withdrawal symptoms: findings from a multi-site, phase 1b/2, randomized, double-blind, placebo-controlled trial. Jones, JD., Rajachandran, L., Yocca, F., et al.[2023]

In a study of seven pediatric patients aged 6 months to 3.75 years, subcutaneous dexmedetomidine was successfully used to treat or prevent drug withdrawal after prolonged sedation, with no withdrawal symptoms observed during treatment.

The use of subcutaneous dexmedetomidine allows for effective administration when intravenous access is challenging, potentially facilitating the removal of central venous catheters and extending its use to home palliative care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous dexmedetomidine infusions to treat or prevent drug withdrawal in infants and children. Tobias, JD.[2019]

Dexmedetomidine is commonly used as a safe sedative during surgeries, but there are rare cases where it can lead to serious complications, such as cardiac arrest.

In this report, a 76-year-old woman experienced cardiac arrest during a pacemaker lead extraction procedure while being treated with dexmedetomidine, highlighting the need for careful monitoring in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Shah, AN., Koneru, J., Nicoara, A., et al.[2013]

In a study involving 91 pediatric patients, dexmedetomidine was found to be a well-tolerated alternative sedative for non-intubated moderate or deep sedation, with a low incidence of serious adverse events.

While respiratory depression and hypotension were the most common treatment-emergent adverse events, they were manageable and consistent with dexmedetomidine's known safety profile, indicating its potential for safe use in children during elective procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. Jooste, EH., Hammer, GB., Reyes, CR., et al.[2020]

In a study of 60 male opioid-addicted patients, using dexmedetomidine during ultra-rapid detoxification under general anesthesia significantly reduced withdrawal symptoms compared to a control group treated with lefoxidine.

Patients receiving dexmedetomidine reported higher satisfaction levels and experienced fewer withdrawal symptoms, particularly in the first few days after recovery from anesthesia, indicating its efficacy in managing opioid withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-rapid opiate detoxification using dexmedetomidine under general anesthesia. Nasr, DA., Omran, HA., Hakim, SM., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine in the treatment of withdrawal syndromes in cardiothoracic surgery patients. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

The impact of perioperative dexmedetomidine infusion on postoperative narcotic use and duration of stay after laparoscopic bariatric surgery. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine to treat opioid withdrawal in infants following prolonged sedation in the pediatric ICU. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Sublingual dexmedetomidine (BXCL501) reduces opioid withdrawal symptoms: findings from a multi-site, phase 1b/2, randomized, double-blind, placebo-controlled trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous dexmedetomidine infusions to treat or prevent drug withdrawal in infants and children. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Ultra-rapid opiate detoxification using dexmedetomidine under general anesthesia. [2015]