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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BXCL501 (sublingual Dexmedetomidine) to help individuals with opioid use disorder manage withdrawal symptoms. The goal is to determine if this treatment can alleviate symptoms like anxiety, muscle pain, and insomnia more effectively than the current non-opioid medication, lofexidine, and a placebo. Participants will receive either BXCL501, lofexidine, or a placebo during their withdrawal period. Individuals with moderate-to-severe opioid use disorder who are physically dependent on opioids might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BXCL501, a form of sublingual dexmedetomidine, is safe and well-tolerated for individuals experiencing opioid withdrawal. In studies, patients experienced fewer issues with blood pressure and heart rhythm compared to those taking lofexidine, a common non-opioid treatment. This resulted in more stable heart rates and blood pressure with BXCL501. Additionally, earlier findings indicated that BXCL501 effectively reduced withdrawal symptoms without major side effects. Overall, early results suggest that BXCL501 could be a safer option for managing opioid withdrawal symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using sublingual dexmedetomidine, known as BXCL501, for opioid withdrawal because it offers a novel approach to managing symptoms. Unlike traditional treatments like methadone or buprenorphine, which primarily target opioid receptors, dexmedetomidine works by calming the central nervous system through a different pathway, the alpha-2 adrenergic receptors. This unique mechanism could provide a new way to ease withdrawal symptoms without the risk of addiction. Additionally, the sublingual delivery method allows for rapid absorption and convenience, which is a significant advantage over treatments that require injections or daily visits to a clinic.

What evidence suggests that this trial's treatments could be effective for opioid withdrawal?

Research shows that sublingual dexmedetomidine, or BXCL501, may help reduce symptoms of opioid withdrawal. In this trial, participants will receive either BXCL501 at doses of 180 or 240 micrograms, lofexidine as a positive control, or a placebo. Studies have found BXCL501 to be safe and well-tolerated, easing symptoms like anxiety and pain during withdrawal. This treatment calms the nervous system, which can lessen withdrawal symptoms. Compared to other medications like lofexidine, BXCL501 is expected to have fewer side effects, particularly regarding blood pressure and heart rhythm. Early findings suggest it could be a better choice for managing withdrawal without using opioids. ^{1 2 3 4 5}

Who Is on the Research Team?

Sandra Comer, Ph.D

Principal Investigator

Columbia University / New York State Psychiatric Institute

Are You a Good Fit for This Trial?

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.

Has moderate-to-severe opioid use disorder (304.00) as per DSM-V, and physiological dependence on opioids.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36630319/

Sublingual dexmedetomidine (BXCL501) reduces opioid ... This study assessed the safety of sublingual dexmedetomidine (BXCL501) and its preliminary efficacy in treating opioid withdrawal.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05712707

Sublingual Dexmedetomidine for Treating Opioid Withdrawal In summary, sublingual dexmedetomidine (BXCL501) is expected to be superior safety and efficacy to other alpha-2a-adrenergic agonists in the treatment of opioid ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11036405/

Sublingual dexmedetomidine (BXCL501) reduces opioid ... In sum, in individuals with physiologic opioid dependence undergoing managed opioid withdrawal, BXCL501 was safe, well-tolerated, and reduced withdrawal ...

4. tandfonline.com tandfonline.com/doi/abs/10.1080/00952990.2022.2144743

Sublingual dexmedetomidine (BXCL501) reduces opioid ... This study assessed the safety of sublingual dexmedetomidine (BXCL501) and its preliminary efficacy in treating opioid withdrawal.

5. ir.bioxceltherapeutics.com ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-update-nida-funded-trial-bxcl501

Press Release Sublingual dexmedetomidine (BXCL501) reduces opioid withdrawal symptoms: findings from a multi-site, phase 1b/2, randomized, double-blind ...