A filmic formulation of research oral dissolution dexmedetomidine (BXCL501, BioXcel Therapeutics) can provide rapid relief from acute agitation related to schizophrenia or bipolar disorder (BD), the results of two phase 3 placebo-controlled randomized trials are shown.
For both disorders, BXCL501 showed “superiority over placebo” in meeting the primary endpoint of agitation reduction measured by the excited component of the Positive and Negative Syndrome Scale (PANSS), study researcher Leslie Citrome, MD, MPH, Department of Psychiatry and Behavioral Sciences, according to New York Medical College, Valhalla, New York Medscape Medical News.
The results were presented at the 2021 annual meeting of the American Psychiatric Association (APA) virtual.
Acute agitation in patients with schizophrenia or BD is often found in emergency departments (EDs) and hospitalization units. When non-pharmacological tactics fail to calm the patient, medication options include injectable antipsychotics or benzodiazepines. BXCL501 is a thin film that dissolves orally for sublingual or buccal use.
“Dexmedetomidine is a highly selective alpha-2a receptor agonist and we haven’t really had any in psychiatry for this purpose. And we haven’t had much of a way to orally dissolve orally thin films that are absorbed orally. mucosa, so this represents an opportunity to provide a potential intervention that does not require an injection, and yet it can be helpful in people who are agitated, ”Citrome said.
The study, known as SERENITY I, included 380 adults (mean age 45.6 years, 63% men) with schizophrenia, schizoaffective disorder, o schizophreniform disorderand acute agitation in the emergency department (total score ≥ 14 on the PANSS excited component (PEC) scale at baseline and score ≥ 4 on at least one of the five PEC items).
Patients were randomly assigned to a single oral dose of BXCL501: 120 mcg, 180 mcg, or placebo. A total of 372 patients (97.9%) completed the study.
The average total PEC score was 17.6 at the beginning. The mean change from baseline in the total PEC score at 2 hours (primary value) was -8.5 and -10.3 with BXCL501 120 mcg and 180 mcg, respectively, versus -4.8 per to placebo (Pg <.0001 vs placebo).
PEC response rates (≥ 40% reduction from baseline) were 80.6% and 89.6% with BXCL501 120 mcg and 180 mcg versus 47.6% with placebo (P .0001 vs placebo).
Compared with placebo, there was a significant improvement in the overall clinical impression improvement (CGI-I) scale with BXCL501 doses at 1 and 2 hours after the dose and at the evaluation scale. agitation and calm (ACES) at 2 hours post-dose.
The incidence of adverse events (AEs) was 39.5%, 37.3%, and 15.1% with the BXCL501 groups of 120 mg, 180 mg, and placebo, respectively.
All AEs were mild or moderate. The most common EAs with BXCL501 were drowsiness, dizziness, dry mouth, hypotension, orthostatic hypotension, hypoaesthesia, and paresthesia. There were no severe or severe drug-related EAs.
Nipping It in the Bud
SERENITY II had a similar design. This study included 380 adults (mean age 48 years, 55% women) with bipolar I or II disorder and acute ED agitation (total score ≥ 14 on the PEC scale at baseline and score ≥ 4 in at least one item PEC). A total of 362 (95.3%) patients completed the study.
The average PEC score was 18 at the beginning. The mean change from baseline in the total PEC score at 2 hours (primary value) was -9.0 and -10.4 with BXCL501 120 mcg and 180 mcg, respectively, versus -4.9 per to placebo (P .0001 vs placebo).
Bipolar patients also saw a significant improvement in CGI-I and ACES secondary outcomes, with an adverse event profile similar to that of patients with schizophrenia.
BXCL501 demonstrated “rapid, robust, and clinically significant efficacy” in both patient populations and represents a “new, noninvasive, and well-tolerated agitation treatment,” the researchers conclude in their APA summaries.
“Patients who are agitated have psychic pain and want to be relieved of this psychic pain. We are also concerned that they may get worse and that the agitation may increase to aggression which may require restrictions. We want to avoid that, ”Citrome said.
“By bursting it with pharmacological intervention, we can relieve your mental pain and we can manage a potentially dangerous situation. Offering an oral medication that works quickly would be ideal for my mind and patients might accept it more than an injection. said Citrome.
Based on SERENITY I and II data, BioXcel Therapeutics has filed a new drug application with the U.S. Food and Drug Administration.
Negotiation first, medication second
Faced with the comments, Samoon Ahmad, MD, a professor in the psychiatry department at New York’s Grossman School of Medicine in New York, warned that “when we talk about treating an agitated patient, medication is only part of the picture.”
“There’s a negotiation process with the patient. First, you provide them with an enabling environment to make them feel calm, safe and secure and to be heard. Providing all of these things can sometimes be very helpful.” said Ahmad, who serves as head of the hospital psychiatry unit at the Bellevue Hospital Center in New York City.
“If someone starts throwing chairs at you or assaulting you, it’s not really the time to negotiate a drug; you basically have to contain the patient and often give them intramuscular medication,” Ahmad said.
He also noted that patients in the SERENITY trials had moderate to severe acute agitation.
“These are people you can negotiate with. But again, when a patient crosses a certain line, you have to do something immediately, which could be an intramuscular injection or something oral, which can spit directly in the face, which has happened numerous times, ”Ahmad said.
“I don’t think intramuscular options go away, but an oral agent can also be a useful tool,” said Ahmad, founder of the New York City Integrative Center for Wellness.
He warned that doctors will not use this drug in their offices. “If a patient comes in and is flourishingly psychotic, you should call 911. We are really talking about their use, either in the emergency room or in the acute hospital,” Ahmad said.
2021 Annual Meeting of the American Psychiatric Association (APA). Filed May 1, 2021.
The SERENITY studies were funded by BioXcel Therapeutics. Several authors have financial relationships with the company. Ahmad did not disclose any relevant financial relationship.