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

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

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

Study Overview

• Status: Terminated
• Conditions: Post-traumatic Stress Disorder (PTSD)
• Intervention / Treatment: Drug: Propranolol; Drug: Prazosin

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • For additional information regarding sites (California, Texas, New Jersey, Minnesota)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sertraline alone at steady state; 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; 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.; Drug: Prazosin; 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.
Active Comparator: Sertraline + brexpiprazole at steady state; 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; 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.; Drug: Prazosin; 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.

What is the study measuring?

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 diastolic blood pressure (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 heart rate (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

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Iqvia Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2022
• Primary Completion (Actual): August 3, 2023
• Study Completion (Actual): August 3, 2023

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): January 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Panic Disorder; Mental disorders; Major Depressive Disorder (MDD); Obsessive-Compulsive Disorder (OCD); Generalized Anxiety Disorder (GAD); Post-traumatic stress disorder (PTSD); Social Anxiety Disorder (SAD)
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Propranolol; Prazosin
• Other Study ID Numbers: 331-201-00246

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No