A Trial to Assess the Effects of Prazosin or Propranolol on Blood Pressure in the Presence of Brexpiprazole/Sertraline

Study Overview
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Brief Summary
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A Trial to Assess the Effects of Prazosin or Propranolol on Blood Pressure in the Presence of Brexpiprazole/Sertraline

Official Title
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A Phase 1, Open-label, Fixed-sequence, Cross-over Trial to Assess the Effects of a Single Dose of Prazosin or Propranolol in the Presence of Brexpiprazole/Sertraline at Steady-state on Blood Pressure

Conditions
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Post-traumatic Stress Disorder (PTSD)

Intervention / Treatment
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* Drug: Propranolol
* Drug: Prazosin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition criteria Diagnosis of Major Depressive Disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, social anxiety disorder or obsessive-compulsive disorder Must be able to receive a sertraline dose of 150 mg/day by the second screening visit (Day -15) Exclusion Criteria Sexually active males or females, who could become pregnant, not agreeing to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days at the end of the study Diagnosed hypertension (including treated or untreated hypertension), or orthostatic hypotension Epilepsy or a history of seizures History of neuroleptic malignant syndrome or serotonin syndrome. Primary DSM-5 diagnosis of Schizophrenia spectrum and other psychotic disorders, Bipolar and related disorders, Feeding and eating disorders (including anorexia nervosa or bulimia), Neurocognitive disorders (including but not limited to delirium, major or mild neurocognitive disorder due to Alzheimer's, Parkinson's, or traumatic brain injury) A significant risk of committing violent acts, serious self-harm, or suicide History of diabetes mellitus (type 1 or type 2) Subjects with any previous exposure to brexpiprazole, or subjects with chronic use of prazosin or propranolol in the 90 days prior to the screening visit or any use in the 21 days (3 weeks) prior to the screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: • Cross-over: participants receive one of two alternative interventions during the initial phase of the study and receive the other intervention during the second phase of the study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sertraline alone at steady state<br>To assess the hemodynamic changes associated with the effects of a single dose of prazosin or propranolol in the presence of brexpiprazole + sertraline at steady state compared with a single dose of prazosin or propranolol in the presence of sertraline alone at steady state. | Drug: Propranolol<br>* Propranolol (tablet, oral ): 40 mg QD Day 3 and Day 21 Intervention 1 is a single dose of prazosin administered in the presence of sertraline alone at steady state or in the presence of sertraline + brexpiprazole at steady state.<br>Drug: Prazosin<br>* Prazosin (tablet, oral): 1 mg QD Day 2 and Day 20 Intervention 2 is a single dose of propranolol administered in the presence of sertraline alone at steady state or in the presence of sertraline + brexpiprazole at steady state.<br>|
| Active Comparator: Sertraline + brexpiprazole at steady state<br>To assess the hemodynamic changes associated with the effects of a single dose of prazosin or propranolol in the presence of brexpiprazole + sertraline at steady state compared with a single dose of prazosin or propranolol in the presence of sertraline alone at steady state. | Drug: Propranolol<br>* Propranolol (tablet, oral ): 40 mg QD Day 3 and Day 21 Intervention 1 is a single dose of prazosin administered in the presence of sertraline alone at steady state or in the presence of sertraline + brexpiprazole at steady state.<br>Drug: Prazosin<br>* Prazosin (tablet, oral): 1 mg QD Day 2 and Day 20 Intervention 2 is a single dose of propranolol administered in the presence of sertraline alone at steady state or in the presence of sertraline + brexpiprazole at steady state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes between the control and treatment periods on Day 19 vs. Day 1, Day 20 vs. Day 2, and Day 21 vs. Day 3, with prazosin or propanolol in the presence of brexpiprazole + sertraline or sertraline alone at steady state | Mean difference in baseline-adjusted change in systolic blood pressure (ΔΔSBP), measured in mmHg, from supine to standing positions will be assessed. | 21 days | 
| Maximum change in SBP, measured in mmHg, from supine to standing position in the presence of brexpiprazole + sertraline or sertraline alone at steady state will be assessed. |  | 21 days | 
| Maximum change in DBP, measured in mmHg, from supine to standing position in the presence of brexpiprazole + sertraline or sertraline alone at steady state will be assessed. |  | 21 days | 
| Maximum change in resting HR, measured in beats per minute (bpm), from supine to standing position will be assessed in the presence of brexpiprazole + sertraline or sertraline alone at steady state will be assessed. |  | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder (MDD), Post-traumatic stress disorder (PTSD), Generalized Anxiety Disorder (GAD), Panic Disorder, Social Anxiety Disorder (SAD), Obsessive-Compulsive Disorder (OCD), Mental disorders