Opioid Use DisorderPhase 1/2NCT05712707
Sublingual Dexmedetomidine for Treating Opioid Withdrawal
A Phase 1/2 study testing BXCL501 (180 micrograms) and BXCL501 (240 micrograms) in people with Opioid Use Disorder and Opioid Withdrawal, run by New York State Psychiatric Institute at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Opioid Use Disorder, Opioid Withdrawal
- What is being tested?
- BXCL501 (180 micrograms) and BXCL501 (240 micrograms)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 4 sitesUnited States
- Study dates
- 28 Feb 2023to 28 Feb 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Capable of understanding and complying with the protocol.
- 18 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Clinilabs
Eatontown, New Jersey, 07724
CenExel HRI
Marlton, New Jersey, 08053
Yale University
New Haven, Connecticut, 06519
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Phase 1B Study of Sublingual Dexmedetomidine, an Alpha 2 Adrenergic Agonist, for Treating Opioid Withdrawal
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.
Read the detailed description
A major challenge to seeking treatment for OUD is the withdrawal syndrome associated with cessation of opioid use. Withdrawal symptoms include irritability, anxiety, muscular and abdominal pains, chills, nausea, diarrhea, yawning, lacrimation, sweating, sneezing, rhinorrhea, general weakness, and insomnia. The intensity of withdrawal symptoms is one of the most common barriers to entering and completing treatment for patients, particularly those who may be interested in maintenance therapy with naltrexone, an opioid antagonist, or buprenorphine, an opioid partial agonist. Because of the short half-life of most illicitly used opioid drugs, such as heroin, withdrawal symptoms reach peak intensity within two to four days after last use, and the duration of withdrawal symptoms usually lasts 7-12 days (Antoine et al., 2021; Cook, 2021).
Currently, there are 2 major strategies to treat withdrawal symptoms after stopping opioid use: Gradual tapering using an opioid drug substitute (methadone or buprenorphine) and amelioration of withdrawal symptoms using alpha-2-adrenergic agonists and other non-opioid medications (benzodiazepines, nonsteroidal anti-inflammatory drugs, etc.) The current gold standard involves gradual reduction of the opioid drug dosage (tapering). The most common opioid withdrawal method is substituting and tapering with methadone or buprenorphine (Srivastava et al., 2020). These are opioid medications with longer half-lives than street opioids and result in more manageable withdrawal symptoms after stopping their use. However, buprenorphine and methadone can be diverted for illicit use, and is associated with adverse events such as respiratory depression, which could be further aggravated by concomitant drug and alcohol use in this population. Furthermore, discontinuation of opioid medications can lead to withdrawal symptoms. A non-opioid medication to facilitate withdrawal suppression from opioid discontinuation in OUD would be of great value.
For over four decades, studies have demonstrated that norepinephrine regulates activity of locus coeruleus neurons, the same neurons that are affected by opioid drugs (Maze et al., 1988). In 1978, several groups reported early successful experience with the use of the alpha-2a-adrenergic agonist clonidine to treat symptoms of opioid withdrawal (Cedarbaum \& Aghajanian, 1977; Gold et al., 1978), which has led to their widespread use for this indication. Opioid physical dependence and withdrawal are mediated at least in part by the interaction of mu-opioid receptors with neurons that contain the neurotransmitter norepinephrine.
Activation of mu-opioid receptors normally suppresses the release of norepinephrine from the locus coeruleus. When opioid use is discontinued or blocked, the locus coeruleus releases excess norepinephrine, and this excess norepinephrine causes many of the withdrawal symptoms noted above. By administering an alpha-2a-adrenergic agonists (like lofexidine, clonidine and dexmedetomidine), hyperactivity of locus coeruleus neurons can be blocked and withdrawal symptoms reduced.
Lofexidine is currently approved in the U.S. for the mitigation of withdrawal symptoms during discontinuation from use of opioids under the brand name Lucemyra. In a recent clinical trial of lofexidine, only 41.5% of the participants taking lofexidine and 27.8% of patients on placebo completed the trial (FDA Approval 2018; Fishman et al., 2019). As a result, patients seeking treatment for illicit opioid use only have an ~4 in 10 chance of completing treatment with the only currently available non-opioid medication, lofexidine. Dexmedetomidine possesses superior pharmacological properties within the alpha-2-adrenergic agonist class. Dexmedetomidine is a full agonist with higher affinity for alpha-2a-adrenergic receptors compared to lofexidine and may be expected to produce a higher level of efficacy (Peltonen et al., 1998, Ouchi \& Sugiyama, 2016; Zhang et al., 2013). *BXCL501 (120 and 180 mcg: IgalmiTM) was recently FDA approved for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.*
Few direct comparisons have been made between dexmedetomidine and lofexidine, but a recent meta-analysis comparing peri-operative adverse events related to dexmedetomidine versus clonidine showed that hypotension was similar for the 2 medications pre- and post-operatively but dexmedetomidine appeared to be protective against hypertension and tachycardia during surgery (Demiri et al., 2019). Furthermore, a trial directly comparing dexmedetomidine (n=144) and clonidine (n=142) in older adults undergoing cardiac surgery showed that dexmedetomidine had superior outcomes with regard to risk and duration of delirium, duration of mechanical ventilation, length of stay in the intensive care unit, mortality rate, and morphine consumption (Shokri \& Ali, 2019). In summary, sublingual dexmedetomidine (BXCL501) is expected to be superior safety and efficacy to other alpha-2a-adrenergic agonists in the treatment of opioid withdrawal.
This study will be first direct comparison of BXCL501 to lofexidine on these outcomes.
- Conditions
- Opioid Use Disorder, Opioid Withdrawal
- Being tested
- BXCL501 (180 micrograms), BXCL501 (240 micrograms), Placebo, Lofexidine (Positive Control)
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 (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.
PlaceboOther
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)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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Study Days 1-7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2023
- Study start28 Feb 2023
- Primary completion30 Jun 2025
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- BioXcel Therapeutics Inc, Yale University, Clinilabs, Inc., National Institute on Drug Abuse (NIDA), CenExel HRI
- Responsible party
- Principal investigator, Sandra D. Comer, New York State Psychiatric Institute
- Investigators
- Sandra Comer, Ph.D, Principal investigator, Columbia University / New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05712707
- Sponsor's protocol ID
- 8325
- Other IDs
- UG3DA056247-01
- Status last verified
- Oct 2026
- First submitted
- 24 Jan 2023
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32572978Srivastava 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.
PubMed 32563380Maze 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.
PubMed 2908485Cedarbaum 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.
PubMed 330174Fishman 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.
PubMed 30531234Shokri 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.
PubMed 31668468
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1B Study of Sublingual Dexmedetomidine, an Alpha 2 Adrenergic Agonist, for Treating Opioid Withdrawal
- ClinicalTrials.gov ID
- NCT05712707
- Acronym / sponsor ID
- 8325
- Conditions
- Opioid Use Disorder, Opioid Withdrawal
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- BioXcel Therapeutics Inc, Yale University, Clinilabs, Inc., National Institute on Drug Abuse (NIDA), CenExel HRI
- Study start
- 28 Feb 2023 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 3 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A major challenge to seeking treatment for OUD is the withdrawal syndrome associated with cessation of opioid use. Withdrawal symptoms include irritability, anxiety, muscular and abdominal pains, chills, nausea, diarrhea, yawning, lacrimation, sweating, sneezing, rhinorrhea, general weakness, and insomnia. The intensity of withdrawal symptoms is one of the most common barriers to entering and completing treatment for patients, particularly those who may be interested in maintenance therapy with naltrexone, an opioid antagonist, or buprenorphine, an opioid partial agonist. Because of the short half-life of most illicitly used opioid drugs, such as heroin, withdrawal symptoms reach peak intensity within two to four days after last use, and the duration of withdrawal symptoms usually lasts 7-12 days (Antoine et al., 2021; Cook, 2021).
Currently, there are 2 major strategies to treat withdrawal symptoms after stopping opioid use: Gradual tapering using an opioid drug substitute (methadone or buprenorphine) and amelioration of withdrawal symptoms using alpha-2-adrenergic agonists and other non-opioid medications (benzodiazepines, nonsteroidal anti-inflammatory drugs, etc.) The current gold standard involves gradual reduction of the opioid drug dosage (tapering). The most common opioid withdrawal method is substituting and tapering with methadone or buprenorphine (Srivastava et al., 2020). These are opioid medications with longer half-lives than street opioids and result in more manageable withdrawal symptoms after stopping their use. However, buprenorphine and methadone can be diverted for illicit use, and is associated with adverse events such as respiratory depression, which could be further aggravated by concomitant drug and alcohol use in this population. Furthermore, discontinuation of opioid medications can lead to withdrawal symptoms. A non-opioid medication to facilitate withdrawal suppression from opioid discontinuation in OUD would be of great value.
For over four decades, studies have demonstrated that norepinephrine regulates activity of locus coeruleus neurons, the same neurons that are affected by opioid drugs (Maze et al., 1988). In 1978, several groups reported early successful experience with the use of the alpha-2a-adrenergic agonist clonidine to treat symptoms of opioid withdrawal (Cedarbaum \& Aghajanian, 1977; Gold et al., 1978), which has led to their widespread use for this indication. Opioid physical dependence and withdrawal are mediated at least in part by the interaction of mu-opioid receptors with neurons that contain the neurotransmitter norepinephrine.
Activation of mu-opioid receptors normally suppresses the release of norepinephrine from the locus coeruleus. When opioid use is discontinued or blocked, the locus coeruleus releases excess norepinephrine, and this excess norepinephrine causes many of the withdrawal symptoms noted above. By administering an alpha-2a-adrenergic agonists (like lofexidine, clonidine and dexmedetomidine), hyperactivity of locus coeruleus neurons can be blocked and withdrawal symptoms reduced.
Lofexidine is currently approved in the U.S. for the mitigation of withdrawal symptoms during discontinuation from use of opioids under the brand name Lucemyra. In a recent clinical trial of lofexidine, only 41.5% of the participants taking lofexidine and 27.8% of patients on placebo completed the trial (FDA Approval 2018; Fishman et al., 2019). As a result, patients seeking treatment for illicit opioid use only have an ~4 in 10 chance of completing treatment with the only currently available non-opioid medication, lofexidine. Dexmedetomidine possesses superior pharmacological properties within the alpha-2-adrenergic agonist class. Dexmedetomidine is a full agonist with higher affinity for alpha-2a-adrenergic receptors compared to lofexidine and may be expected to produce a higher level of efficacy (Peltonen et al., 1998, Ouchi \& Sugiyama, 2016; Zhang et al., 2013). *BXCL501 (120 and 180 mcg: IgalmiTM) was recently FDA approved for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.*
Few direct comparisons have been made between dexmedetomidine and lofexidine, but a recent meta-analysis comparing peri-operative adverse events related to dexmedetomidine versus clonidine showed that hypotension was similar for the 2 medications pre- and post-operatively but dexmedetomidine appeared to be protective against hypertension and tachycardia during surgery (Demiri et al., 2019). Furthermore, a trial directly comparing dexmedetomidine (n=144) and clonidine (n=142) in older adults undergoing cardiac surgery showed that dexmedetomidine had superior outcomes with regard to risk and duration of delirium, duration of mechanical ventilation, length of stay in the intensive care unit, mortality rate, and morphine consumption (Shokri \& Ali, 2019). In summary, sublingual dexmedetomidine (BXCL501) is expected to be superior safety and efficacy to other alpha-2a-adrenergic agonists in the treatment of opioid withdrawal.
This study will be first direct comparison of BXCL501 to lofexidine on these outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| BXCL501 (180 micrograms) | Experimental | Drug: BXCL501 (180 micrograms)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. |
| BXCL501 (240 micrograms) | Experimental | Drug: BXCL501 (240 micrograms)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. |
| Lofexidine (Positive Control) | Active comparator | Other: Lofexidine (Positive Control)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. |
| Placebo | Placebo comparator | Other: PlaceboThe 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Capable of understanding and complying with the protocol.
- 18 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.
Key exclusion criteria (12 listed)
- 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)].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BXCL501 (180 micrograms)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. | Drug | BXCL501 (180 micrograms) |
| BXCL501 (240 micrograms)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. | Drug | BXCL501 (240 micrograms) |
| PlaceboThroughout 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. | Other | Placebo |
| Lofexidine (Positive Control)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. | Other | Lofexidine (Positive Control) |
Primary outcome
Safety of BXCL501 versus Placebo and Lofexidine
Time frame: Study Days 1-7
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Background: PubMed 32572978Antoine 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.
- Background: PubMed 32563380Srivastava 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.
- Background: PubMed 2908485Maze 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.
- Background: PubMed 330174Cedarbaum 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandra Comer, Ph.D principal investigator
Columbia University / New York State Psychiatric Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BXCL501 (180 micrograms) and BXCL501 (240 micrograms) in people with Opioid Use Disorder and Opioid Withdrawal, run by New York State Psychiatric Institute at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of BXCL501 versus Placebo and Lofexidine (time frame: Study Days 1-7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05712707, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026; AzTrials last refreshed its copy on 6 Nov 2026.