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Also known as BXCL501 (180 micrograms), BXCL501 80 Micrograms, BXCL501 120 Micrograms, BXCL501 60 Micrograms, Dexmedetomidine, Sublingual film containing Igalmi, Sublingual film containing Dexmedetomidine
BXCL501 · 6 trials · 16 indications
The Positive and Negative Syndrome Scale - Excited Component (PEC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC, the sum of these 5 subscales, thus ranges from 5 (absence of agitation) to 35 (extremely severe)
To assess the safety of 120 mcg BXCL501 when used in an at-home environment based on serious adverse events (SAE) and treatment emergent adverse events (TEAEs).
The Positive and Negative Syndrome Scale - Excited Component (PEC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC, the sum of these 5 subscales, thus ranges from 5 (absence of agitation) to 35 (extremely severe)
Anxiety is measured via blood pressure (systolic and diastolic). Participants will undergo stress (PTSD) reactivity conditions (both neutral and trauma) on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in blood pressure is computed as the difference in measurements taken across the PTSD Reactivity Conditions to the measurement collected immediately prior to the stress condition.
Anxiety is measured via heart rate. Participants will undergo stress (PTSD) reactivity conditions (both neutral and trauma) on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in heart rate is computed as the difference in measurements taken across the PTSD Reactivity Conditions to the measurement collected immediately prior to the stress condition.
Anxiety is measured via the State Trait Anxiety Inventory (STAI-6). Participants will undergo stress (PTSD) reactivity conditions (both neutral and trauma) on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in STAI-6 score is computed as the difference in measurements taken across the PTSD Reactivity Conditions to the measurement collected immediately prior to the stress condition.
Alcohol craving is measured via the Yale Craving Scale (score range is 0 to 112, with 0 meaning "no sensation" and 112 meaning "strongest imaginable sensation of any kind"). Participants will undergo stress (PTSD) reactivity conditions (both neutral and trauma) on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in YCS is computed as the difference in measurements taken across the PTSD Reactivity Conditions to the measurement collected immediately prior to the stress condition.
Mood disturbance is measured via the Drugs Effects Questionnaire (DEQ). Participants will undergo stress (PTSD) reactivity conditions (both neutral and trauma) on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in DEQ is computed as the difference in measurements taken across the PTSD Reactivity Conditions to the measurement collected immediately prior to the stress condition.
Mood disturbance is measured via the Visual Analog Scale (score range is 0 to 100, with 0 having no specific mood disturbance and 100 having extreme specific mood disturbance). Participants will undergo stress (PTSD) reactivity conditions (both neutral and trauma) on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in VAS is computed as the difference in measurements taken across the PTSD Reactivity Conditions to the measurement collected immediately prior to the stress condition.
Anxiety is measured via blood pressure (systolic and diastolic). Participants will undergo an alcohol cue reactivity condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in blood pressure is computed as the difference in measurements taken across the alcohol reactivity conditions to the measurement collected immediately prior to the alcohol reactivity condition.
Anxiety is measured via heart rate. Participants will undergo an alcohol cue reactivity condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in heart rate is computed as the difference in measurements taken across the alcohol reactivity conditions to the measurement collected immediately prior to the alcohol reactivity condition.
Anxiety is measured via the State Trait Anxiety Inventory (STAI-6). Participants will undergo an alcohol cue reactivity condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in STAI-6 score is computed as the difference in measurements taken across the alcohol reactivity conditions to the measurement collected immediately prior to the alcohol reactivity conditions.
Alcohol craving is measured via the Yale Craving Scale (score range is 0 to 112, with 0 meaning "no sensation" and 112 meaning "strongest imaginable sensation of any kind"). Participants will undergo an alcohol cue reactivity condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in YCS is computed as the difference in measurements taken across the alcohol reactivity conditions to the measurement collected immediately prior to the alcohol reactivity conditions
Mood disturbance is measured via the Drugs Effects Questionnaire (DEQ). Participants will undergo an alcohol cue reactivity condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in DEQ is computed as the difference in measurements taken across the alcohol cue reactivity condition to the measurement collected immediately prior to the alcohol cue reactivity condition.
Mood disturbance is measured via the Visual Analog Scale (score range is 0 to 100, with 0 having no specific mood disturbance and 100 having extreme specific mood disturbance). Participants will undergo an alcohol cue reactivity condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in VAS is computed as the difference in measurements taken across the alcohol cue reactivity condition to the measurement collected immediately prior to the alcohol cue reactivity condition.
The BAES is a 14-item self-report adjective rating scale that will serve to measure stimulant and sedative effects of alcohol. The Stimulation subscale score range is 0 to 70, with higher scores indicating greater stimulation. The Sedation subscale score range is 0 to 70, with higher scores indicating greater sedation. Participants will undergo alcohol infusion condition on laboratory test days 1, 2, and 3 (receiving either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), change in BAES score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion. Differences in the change in BAES score will be compared across all three treatment arms.
Self-rated alcohol intoxication is measured by the Number of Drinks Scale (NDS). The NDS assess how many drinks the subject feels he/she has consumed at a specific timepoint (the higher the number the greater the alcohol intoxication). Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in NDS score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion. Differences in the change in NDS score will be compared across all three treatment arms.
The STAI-6 is a 6-item measure designed to assess trait and state aspects of anxiety. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in STAI-6 score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion. Differences in the change in STAI-6 score will be compared across all three treatment arms.
The DEQ is a 5-item self-report measure used to assess the two key aspects of the subjective experience of substance effects: (1) the strength of substance effects and (2) the desirability of substance effects. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in DEQ score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion. Differences in the change in DEQ score will be compared across all three treatment arms.
Alcohol craving is measured via the Yale Craving Scale (score range is 0 to 112, with 0 meaning "no sensation" and 112 meaning "strongest imaginable sensation of any kind"). Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in YCS score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion. Differences in the change in YCS score will be compared across all three treatment arms.
Mood disturbance is measured via the Visual Analog Scale (score range is 0 to 100, with 0 having no specific mood disturbance and 100 having extreme specific mood disturbance). Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in VAS score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion. Differences in the change in VAS score will be compared across all three treatment arms.
The GPB is a manipulative dexterity test, consisting of a board with randomly positioned slots in which subjects insert pegs. It is an eye-to-hand coordination test that has been used in research studies to measure motor skills. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in GPB score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to drug administration. Differences in the change in GPB score will be compared across all three treatment arms.
The RVIP is a widely used task to assess sustained attention, with a working memory component. These cognitive functions are sensitive to acute alcohol administration. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in RVIP score is computed as the difference in the RVIP measurement taken once the targeted BAL is achieved during the alcohol infusion to the measurement collected immediately prior to drug administration.
The HVLT-R is a word list learning test of verbal memory and is sensitive to the acute effects of alcohol. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in HVLT-R score is computed as the difference in the HVLT-R measurement taken once the targeted BAL is achieved during the alcohol infusion to the measurement collected immediately prior to drug administration.
The Go No-Go task will assess the ability to withhold responses to an infrequently occurring target (No-Go trials). Alcohol has been shown to impair responses to Go No-Go task. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in Go No-Go score is computed as the difference in the Go No-Go measurement taken once the targeted BAL is achieved during the alcohol infusion to the measurement collected immediately prior to drug administration.
Potential side-effects of BXCL501 in the presence of alcohol will be measured via blood pressure. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in blood pressure is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion.
Potential side-effects of BXCL501 in the presence of alcohol will be measured via heart rate. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in heart rate is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion.
Potential side-effects of BXCL501 in the presence of alcohol will be measured via the RASS, which is assessed by clinic staff to measure participant's level of sedation. The score range is +4 (combative) to -5 (unarousable), thus lower scores indicate greater sedation. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in RASS score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion.
Potential side-effects of BXCL501 in the presence of alcohol will be measured via the ACES, which is assessed by clinic staff to measure participants' level of sedation. The score range is 1 (marked agitation) to 9 (unarousable), thus higher scores indicate greater sedation. Participants will undergo an alcohol infusion condition on laboratory test days 1, 2, and 3 (where participant receives either BXCL501 40µg, 80µg, or placebo in a randomized fashion each day). For each test day (1-3), the change in ACES score is computed as the difference in measurements taken across the alcohol infusion to the measurement collected immediately prior to the alcohol infusion.
Participants will undergo vital signs on baseline, day 5, day 7, and weeks 2-4. The change in blood pressure is computed as the difference in measurements taken across all study timepoints from the baseline visit (pre-treatment).
Participants will take the STAI-6 assessment on baseline, day 5, day 7, and weeks 2-4. The change in STAI-6 score is computed as the difference in measurements taken across all study timepoints from the baseline visit (pre-treatment).
Adverse Events will be monitored and documented through each dose escalation phase after the first dose administration.
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.
The Positive and Negative Syndrome Scale - Excited Component (PEC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC, the sum of these 5 subscales, thus ranges from 5 (absence of agitation) to 35 (extremely severe)
| Arm | Type | Description |
|---|---|---|
| Part 1: 60 mcg of BXCL501 | EXPERIMENTAL | Sublingual film containing 60 Micrograms Dexmedetomidine |
| Part 1: Matching Placebo | PLACEBO_COMPARATOR | Sublingual Placebo film |
| Part 2: 120 mcg of BXCL501 | EXPERIMENTAL | Sublingual film containing 120 Micrograms Dexmedetomidine |
| Part 2: Matching Placebo | PLACEBO_COMPARATOR | Sublingual Placebo film |
| Cohort 1- 40 Micrograms | EXPERIMENTAL | Sublingual film containing 40 Micrograms Dexmedetomidine |
| Cohort 2- 60 Micrograms | EXPERIMENTAL | Sublingual film containing 60 Micrograms Dexmedetomidine |
| Placebo | PLACEBO_COMPARATOR | Sublingual Placebo film |
| Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 40µg | EXPERIMENTAL | BXCL501 is a thin film formulation of dexmedetomidine (DEX) for sublingual (SL) administration. The product is a small, solid-dose film formulation, approximately 286 mm2 in area and 0.7 mm thick, designed to solubilize in the SL space within 1-3 minutes. At the time of dosing, subjects will be verbally instructed on how to take the investigational product sublingually, and that they should retain the investigational product in the sublingual cavity until dissolved. |
| Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 80µg | EXPERIMENTAL | BXCL501 is a thin film formulation of dexmedetomidine (DEX) for sublingual (SL) administration. The product is a small, solid-dose film formulation, approximately 286 mm2 in area and 0.7 mm thick, designed to solubilize in the SL space within 1-3 minutes. At the time of dosing, subjects will be verbally instructed on how to take the investigational product sublingually, and that they should retain the investigational product in the sublingual cavity until dissolved. |
| BXCL501 Dose Range 40µg to 160µg | OTHER | Participants will receive 40µg on days 1-2. On days 3 and 4, participants will receive 40µg twice per day. On days 5 and 6 participants will receive 40µg in the morning and 80µg in the evening. On days 7-28 participants will receive 80µg in the morning and evening. Dose escalation will follow the above schedule based on tolerability assessed by clinician. |
| 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. |
| 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. |
| 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. |
| 80 Micrograms | EXPERIMENTAL | Sublingual film containing 80 micrograms Dexmedetomidine |
| 120 Micrograms | EXPERIMENTAL | Sublingual film containing 120 micrograms Dexmedetomidine |
| 60 Micrograms | EXPERIMENTAL | Sublingual film containing 60 micrograms Dexmedetomidine Europe Only |
| Name | Type | Description |
|---|---|---|
| BXCL501 | DRUG | Sublingual Film |
| Matching Placebo | DRUG | Sublingual Placebo Film |
| Placebo | DRUG | Placebo will be administered orally, as individual films in the SL space. |
| Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 40µg | DRUG | BXCL 501 40µg will be administered orally, as individual films in the SL space. |
| Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 80µg | DRUG | BXCL 501 80µg will be administered orally, as individual films in the SL space. |
| Ethanol Infusion | PROCEDURE | Study team will be using a modified alcohol-IV clamp procedure developed and standardized by Subramanian and colleagues (Subramanian, Heil et al. 2002). The infusion will be performed using a 6% ethanol solution in 0.9% saline. The computer assisted administration program automatically calculates and corrects the infusion rate based on real-time BrAC data entry by staff, based on the pharmacokinetic profile of each subject (targeting a breath alcohol concentration (BrAC) of 100 mg%). |
| PTSD Reactivity Condition | BEHAVIORAL | Participants will be exposed to two conditions in random order: PTSD cues and neutral cues. The cues will consist of a 5 minute presentation of the stimulus (trauma or neutral) followed by immediate evaluation of craving and anxiety. There will be a relaxation procedure between each condition. The imagery scripts are developed based on the scene construction questionnaire developed by Lang et al (Lang, Kozak et al. 1980, Lang, Levin et al. 1983) using a standardized format designed by Sinha (Sinha 2001). |
| Alcohol Cue Reactivity | BEHAVIORAL | Participants will be exposed to two conditions: a neutral cue (water) followed by an alcohol cue. Individuals will be instructed that they may smell and handle the beverage, but they cannot consume the beverage. Following the presentation, the research assistant takes the beverage and leaves the room, while the subject completes the anxiety and alcohol craving assessments. |
| 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. |
| 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. |
| BXCL501 80 Micrograms | DRUG | Sublingual film containing 80 Micrograms BXCL501 |
| Placebo Film | DRUG | Matching Sublingual Placebo film |
| BXCL501 120 Micrograms | DRUG | Sublingual film containing 120 Micrograms BXCL501 |
| BXCL501 60 Micrograms | DRUG | Sublingual film containing 60 Micrograms BXCL501 Europe Only |
A patient may enroll in only one part of the study; either Part 1 or Part 2. Inclusion Criteria: * Male and female patients between the ages of 18 to 75 years, inclusive * Patients who can read, understand and provide written informed consent. * Patients who have met Diagnostic and Statistical Man...
BXCL501 is being developed to treat agitation, including agitation associated with schizophrenia and bipolar disorder, and agitation associated with dementia. It is also being studied in alcohol use disorder and opioid withdrawal. It is an investigational sublingual formulation and has not been approved by the FDA.
BXCL501 is developed by BioXcel Therapeutics, Inc., which trades on the Nasdaq under the ticker BTAI. The company is the sponsor of the clinical program for the sublingual dexmedetomidine formulation.
BXCL501 is in Phase 3 development. Two Phase 3 trials have been completed: SERENITY III in agitation associated with schizophrenia and bipolar disorder, and TRANQUILITY II in agitation associated with dementia. Additional Phase 1 studies are ongoing or active.
BXCL501 has been studied in NCT05658510 (SERENITY III, Phase 3, completed, 452 patients) and NCT05271552 (TRANQUILITY II, Phase 3, completed, 151 patients). Ongoing or active Phase 1 trials include NCT06335407 in alcohol use disorder and PTSD, and NCT05712707 in opioid withdrawal.
BXCL501 is a sublingual formulation of dexmedetomidine, also referred to as dexmedetomidine hydrochloride (HCl) for sublingual administration. It is also known by dose-specific names such as BXCL501 60 micrograms, BXCL501 80 micrograms, and BXCL501 120 micrograms.
BXCL501 has received Breakthrough Therapy and Fast Track designations from the FDA. These designations are intended to expedite the development and review of drugs for serious conditions. BXCL501 remains investigational and is not approved for any indication.