An experimental orally dissolving film formulation of dexmedetomidine (BXCL501, BioXcel Therapeutics) may provide rapid relief from acute agitation associated with schizophrenia or bipolar disorder (TB), according to the results of two phase 3, randomized and controlled trials. placebo-controlled.
For both disorders, BXCL501 showed “superiority over placebo” by achieving the primary endpoint of reduction in agitation as measured by the excited component of the Positive and Negative Syndrome Scale (PANSS), investigator of the ‘study, Leslie Citrome, MD, MPH, Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York, said Medscape Medical News.
The results were presented at the 2021 American Psychiatric Association (APA) Virtual Annual Meeting.
Acute agitation in patients with schizophrenia or TB is often encountered in emergency departments (ED) and inpatient units. When non-drug tactics fail to calm the patient, drug options include injectable antipsychotics or benzodiazepines. BXCL501 is an orally dissolving thin film intended for sublingual or buccal use.
“Dexmedetomidine is a highly selective alpha-2a agonist and we have never had one before in psychiatry for this purpose. And we didn’t have much to orally dissolve orally absorbed thin films. mucosa so this represents an opportunity to provide a potential intervention that does not require an injection and yet could be useful in agitated people, ”said Citrome.
The study, known as SERENITY I, included 380 adults (mean age 45.6 years, 63% male) with schizophrenia, schizoaffective disorder or schizophreniform disorder and acute agitation on the ward. emergencies (total score ≥ 14 on the PANSS-Excited (PEC) component at baseline and a 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 mean total PEC score was 17.6 at baseline. The mean change from baseline in the 2-hour PEC total score (primary endpoint) was -8.5 and -10.3 with BXCL501 120 mcg and 180 mcg, respectively, versus -4.8 for placebo (P <.0001 vs placebo>
The response rates to PEC (≥ 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, a significant improvement in the Clinical Global Impression Improvement Scale (CGI-I) was observed with the two doses of BXCL501 1 and 2 hours after administration and in the scale of Agitation and Calm Assessment (ACES) 2 hours after administration.
The incidence of adverse events (AEs) was 39.5%, 37.3% and 15.1% with the BXCL501 120 mg, 180 mg and placebo groups.
All AEs were mild or moderate. The most common AEs with BXCL501 were drowsiness, dizziness, dry mouth, hypotension, orthostatic hypotension, hypoaesthesia, and paresthesia. No serious or serious drug-related AEs occurred.
Nibble on the bud
SERENITY II had a similar design. This study included 380 adults (mean age 48 years, 55% female) with bipolar I or II disorder and acute agitation in the emergency department (total score ≥ 14 on the PEC scale at baseline and score ≥ 4 on at least one PEC item). A total of 362 (95.3%) of the patients completed the study.
The mean total PEC score was 18 at baseline. The mean change from baseline in the 2-hour PEC total score (primary endpoint) was -9.0 and -10.4 with BXCL501 120 mcg and 180 mcg, respectively, versus -4.9 for placebo (P .0001 vs placebo).
Bipolar patients also saw significant improvement in secondary outcomes from CGI-I and ACES, with an adverse event profile similar to that seen in patients with schizophrenia.
BXCL501 has demonstrated “rapid, robust and clinically significant efficacy” in both patient populations and represents “an innovative, non-invasive and well-tolerated treatment for agitation,” the researchers conclude in their APA summaries.
“Patients who are agitated suffer from psychic pain and they want relief from that psychic pain. We are also concerned that it will get worse and the agitation will escalate into aggression potentially requiring restraint. We want to avoid that.” , said Citrome.
“By nipping it in the bud with pharmacological intervention, we can ease their psychological pain and we can handle a potentially dangerous situation. Offering an oral medication that would work quickly would be ideal in my mind and patients could potentially accept it more. than an injection, ”Citrome said.
Based on SERENITY I and II data, BioXcel Therapeutics submitted a new drug application to the United States Food and Drug Administration.
Negotiation first, drugs second
Contacted for comment, Samoon Ahmad, MD, professor, Department of Psychiatry, NYU Grossman School of Medicine, New York, warned that “when we talk about treating an agitated patient, drugs are only part of the picture.”
“There is a process of negotiation with the patient. First, you provide him with an environment that allows him to feel calm, safe, and secure and that he is listened to. Providing all of these things can sometimes be very helpful ”. said Ahmad, who is unit chief of inpatient psychiatry at Bellevue Hospital Center in New York City.
“If someone starts throwing chairs or assaulting you, now’s not really the time to negotiate a drug; you basically have to restrain the patient, and often give him intramuscular drugs, ”Ahmad said.
He also noted that patients in the SERENITY trials had moderate to severe acute agitation.
“These are people you can potentially negotiate with. But again when a patient crosses a certain line you have to do something immediately and it can be an intramuscular injection or something taken by mouth, which he can spit directly into the face, which has happened in many cases. times. times, ”Ahmad said.
“I don’t think intramuscular options will ever go away, but an oral agent could also be a useful tool,” said Ahmad, founder of the Integrative Center for Wellness in New York City.
He warned that clinicians would not use the drug in their offices. “If a patient comes in and is deeply psychotic you will need to call 911. We are really talking about its use either in the emergency department or in an acute hospital setting,” Ahmad said.
American Psychiatric Association (APA) 2021 Annual Meeting. Presented May 1, 2021.
The SERENITY studies were funded by BioXcel Therapeutics. Several authors maintain financial relations with the company. Ahmad did not disclose any relevant financial relationship.
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