Clinical trial NCT06093451: Evaluating Sublingual Dexmedetomidine For Moderate To Severe Agitation In Inpatients With Schizophrenia Or Bipolar Disorder
Official title: An Open-Label, Randomized, Active Controlled Inpatient Trial Evaluating Sublingual Dexmedetomidine For Moderate To Severe Agitation In Inpatients With Schizophrenia Or Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Schizophrenia Agitation
Schizo Affective Disorder
Bipolar Disorder
Dexmedetomidine
Keywords: Agitation
Schizophrenia
Schizoaffective Disorder
Bipolar Disorder
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: BioXcel Therapeutics Inc
First posted: 2023-10-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An open-label, randomized, active control inpatient trial to evaluate the efficacy and tolerability of sublingual dexmedetomidine for the treatment of agitation in inpatients with schizophrenia or bipolar disorder as measured by the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES). Lorazepam will serve as the active control.

Detailed description: This is an open-label, randomized control trial where patients (N=32) with schizophrenia or bipolar disorder are randomized to receive either sublingual dexmedetomidine or oral lorazepam monotherapy for the treatment of episodic agitation. For moderate agitation (PANSS-EC score ≥14 and \<20), patients will receive either sublingual dexmedetomidine 120mcg or oral lorazepam 2mg. For severe agitation (PANSS-EC ≥20), patients will receive either sublingual dexmedetomidine 180mcg or oral lorazepam 2mg. The PANSS-EC and ACES will be evaluated at baseline and after 15, 30, 60, and 120 minutes.

Eligibility criteria: Inclusion Criteria:

* The participant is an adult between the ages of 18-55 at the time of study participation
* Hospitalized on an inpatient unit at Episcopal Hospital
* Meet the DSM-5 criteria for schizophrenia, schizoaffective disorder, or bipolar disorder, as determined by routine clinical assessment conducted upon admission.
* Are able to understand and read English
* Are able to provide informed consent
* Experiencing a moderate (PANSS-EC score ≥14 and \<20) or severe (PANSS-EC score ≥20) episode of agitation

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* Prisoners
* Participant has an allergy to dexmedetomidine or lorazepam
* Participant has mild, moderate or severe hepatic impairment
* Participant has active pulmonary disease and is receiving treatment (oxygen, inhalers)
* Individual is currently prescribed scheduled benzodiazepines or methadone
* Participant history of QTc ≥ 500 msec or a history of arrythmia
* Participant recent (within the last 2 days) fall, syncope (passing out), feeling lightheaded, or pulse \<50.
* Individual has a history of hypokalemia or hypomagnesemia within the past 2 years?
* Participant is receiving high-risk medications, including:

  1. Methadone
  2. Midazolam
  3. Opioids
  4. High risk medications associated with the QT interval prolongation (sertindole, chlorpromazine, ziprasidone), (amiodarone, iboga, quinine, arsenic, ibutilide, selpercatinib, ivosidenib, bedaquiline, lenvatinib, sotalol, levoketoconazole, cisapride, vendetanib, mobocertinib, disopyramide, papaverine)

Primary outcomes:
measure: Change in PANSS-EC score at 120 minutes after medication administration
timeFrame: Baseline and at 120 minutes
Secondary outcomes:
measure: Change from baseline in ACES score at 15, 30, 60, 90, and 120 minutes, or prior to receipt of any rescue medication for agitation.
timeFrame: Baseline and 15, 30, 60, 90, and 120 minutes
measure: Change in PANSS-EC score at 15, 30, 60, and 90 minutes, or prior to receipt of any rescue medication for agitation.
timeFrame: Baseline and 15, 30, 60, and 90 minutes
measure: Patient tolerability assessed by adverse events of dexmedetomidine
timeFrame: Baseline through 120 minutes after medication administration
measure: Patient satisfaction based on Medication Satisfaction Questionnaire (MSQ)
timeFrame: Administered 120 minutes after medication administration
measure: Assess the need for rescue medication for agitation within two hours of medication administration
timeFrame: Baseline and 2 hours after medication administration
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Temple University Episcopal Hospital
state: Pennsylvania
Study officials:
References:
citation: San L, Marksteiner J, Zwanzger P, Figuero MA, Romero FT, Kyropoulos G, Peixoto AB, Chirita R, Boldeanu A. State of Acute Agitation at Psychiatric Emergencies in Europe: The STAGE Study. Clin Pract Epidemiol Ment Health. 2016 Oct 27;12:75-86. doi: 10.2174/1745017901612010075. eCollection 2016.
citation: Cots F, Chiarello P, Perez V, Gracia A, Becerra V. Hospital Costs Associated With Agitation in the Acute Care Setting. Psychiatr Serv. 2016 Jan;67(1):124-7. doi: 10.1176/appi.ps.201400508. Epub 2015 Aug 3.
citation: Rubio-Valera M, Luciano JV, Ortiz JM, Salvador-Carulla L, Gracia A, Serrano-Blanco A. Health service use and costs associated with aggressiveness or agitation and containment in adult psychiatric care: a systematic review of the evidence. BMC Psychiatry. 2015 Mar 4;15:35. doi: 10.1186/s12888-015-0417-x.
citation: Richmond JS, Berlin JS, Fishkind AB, Holloman GH Jr, Zeller SL, Wilson MP, Rifai MA, Ng AT. Verbal De-escalation of the Agitated Patient: Consensus Statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup. West J Emerg Med. 2012 Feb;13(1):17-25. doi: 10.5811/westjem.2011.9.6864.
citation: Wilson MP, Pepper D, Currier GW, Holloman GH Jr, Feifel D. The psychopharmacology of agitation: consensus statement of the american association for emergency psychiatry project Beta psychopharmacology workgroup. West J Emerg Med. 2012 Feb;13(1):26-34. doi: 10.5811/westjem.2011.9.6866.
citation: Zeller SL, Citrome L. Managing Agitation Associated with Schizophrenia and Bipolar Disorder in the Emergency Setting. West J Emerg Med. 2016 Mar;17(2):165-72. doi: 10.5811/westjem.2015.12.28763. Epub 2016 Mar 2.
citation: Preskorn SH, Zeller S, Citrome L, Finman J, Goldberg JF, Fava M, Kakar R, De Vivo M, Yocca FD, Risinger R. Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated With Bipolar Disorder: A Randomized Clinical Trial. JAMA. 2022 Feb 22;327(8):727-736. doi: 10.1001/jama.2022.0799.
citation: Citrome L, Preskorn SH, Lauriello J, Krystal JH, Kakar R, Finman J, De Vivo M, Yocca FD, Risinger R, Rajachandran L. Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. J Clin Psychiatry. 2022 Oct 3;83(6):22m14447. doi: 10.4088/JCP.22m14447.
citation: Igalmi [package insert]. BioXcel Therapeutics, Inc; 2022.