# Phase 1 and 2 studies of sublingual dexmedetomidine, an alpha 2 adrenergic agonist, for treating opioid withdrawal

> **NIH NIH UG3** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2022 · $3,312,204

## Abstract

Project Summary
The current epidemic of Opioid Use Disorder (OUD) is a severe public health crisis in the US, and in response,
the National Institutes of Health (NIH) is supporting development of innovative medications for treating OUD.
The withdrawal symptoms associated with cessation of opioid use are serious obstacles to initiating opioid
blockers (naltrexone) and may pose difficulties in transitioning patients to other medications for treating opioid
use disorder (MOUD), such as buprenorphine. The FDA approval of the alpha-2-adrenergic agonist lofexidine
has made a significant contribution to ameliorating OUD withdrawal, but only 40% of subjects became opioid
free in a pivotal study. This study was conducted prior to the widespread availability of the potent synthetic
opioid fentanyl, so the effectiveness of lofexidine in treating opioid withdrawal in fentanyl-dependent patients is
unclear. BioXcel has developed another alpha-2-adrenergic agonist dexmedetomidine as a sublingual (SL) film
(BXCL501). BXCL501 is potentially superior to alternatives such as opioid tapering because it is a non-opioid
with minimal abuse potential, and at doses that reduce opioid withdrawal symptoms, it has minimal adverse effects
on respiration, hypotension, hypertension, bradycardia, and sedation. Furthermore, it avoids potential liver
complications due to bypassing first-pass metabolism. Data collected during a recently completed multiple
ascending dose safety and preliminary efficacy study showed that the highest dose of BXCL501 tested
reduced anxiety and improved sleep disturbances, which are symptoms that are typically not well treated with
lofexidine. In the proposed studies, BXCL501 will be tested for its ability to decrease the signs and symptoms
of opioid withdrawal across multiple sites through two Specific Aims: 1 (UG3). A Phase 1b randomized, double-
blind, placebo-controlled safety, optimal dose finding, and preliminary efficacy inpatient study (n=160), and 2
(UH3). A Phase 2b randomized, double-blind, placebo-controlled outpatient study comparing the safety and
efficacy of BXCL501 to placebo and lofexidine (n=300). Two Go/No-Go criteria for moving from the UG3 to the
UH3 phases are: 1) BXCL501 is shown to reduce withdrawal symptoms (total SOWS score) more than 30%
compared to the SOWS score of subjects receiving placebo. 2) No more than one serious adverse event
attributed to BXCL501 among the subjects receiving active BXCL at the minimum dose identified to exhibit at
least a 30% reduction in withdrawal symptoms. Our positive clinical findings with BXCL501 and strong
investigative team promise high success for bringing this new treatment to market.

## Key facts

- **NIH application ID:** 10478324
- **Project number:** 1UG3DA056247-01
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** SANDRA D. COMER
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,312,204
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478324

## Citation

> US National Institutes of Health, RePORTER application 10478324, Phase 1 and 2 studies of sublingual dexmedetomidine, an alpha 2 adrenergic agonist, for treating opioid withdrawal (1UG3DA056247-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10478324. Licensed CC0.

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