Clinical trial NCT02968121: Safety and Tolerability Study of Single-dose Administration of Brexpiprazole in Adult Subjects With Schizophrenia
Official title: A Phase 1, Two-part, Open-label, Randomized, Exploratory and Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Brexpiprazole Long-acting Injectable Administered Subcutaneously or Intramuscularly in Adult Subjects With Schizophrenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Schizophrenia
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2016-11-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: To determine the pharmacokinetics, safety and tolerability of brexpiprazole administered subcutaneously or intramuscularly in adults with schizophrenia.

Detailed description: This trial is designed to assess the pharmacokinetics, safety and tolerability of brexpiprazole in the treatment of subjects with schizophrenia. The trial will consist of two parts across 13-36 months. The trial population will include approximately 110 male \& female subjects between 18 and 64 years of age (inclusive) with a diagnosis of schizophrenia as defined by DSM-V criteria.

Eligibility criteria: Inclusion Criteria:

* Males and females between 18 and 64 years of age, inclusive, at the screening visit with a diagnosis of schizophrenia as defined by DSM-V criteria.
* Body mass index between 18 and 35 kg/m\^2 at the screening visit.
* Good physical health as determined by no clinically significant deviation from normal.
* Ability to provide informed consent and/or consent obtained from a legally acceptable representative (as required by IRB), prior to the initiation of any protocol-required procedures.
* Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to the screening visit, or male subjects/female subjects (of childbearing potential) who agree to remain abstinent or to practice 2 of the approved birth control methods from the screening visit and for at least 150 days after the dose of IMP for a female subject or 180 days after the dose of IMP for a male subject.

Exclusion Criteria:

* Subjects who have:
* Met DSM-V criteria for substance use disorder within the past 180 days; including alcohol and benzodiazepines, excluding caffeine/nicotine.
* A positive drug screen for drugs of abuse (excluding stimulants, other prescribed medications, and marijuana \[if in investigator's documented opinion the subject does not meet DSM-V criteria for substance use disorder\]).
* Use of more than 1 psychotropic medication at the screening or baseline visit, except for oral brexpiprazole administered during the brexpiprazole tolerability testing (if applicable) and current oral antipsychotic medication.
* Use of varenicline beyond screening.
* Subjects who have participated in any clinical trial involving a psychotropic medication within 1 month prior to the administration of IMP or 5 half-lives from last IMP administration whichever is longer.
* Subjects who have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on questions 4 or 5 on the Baseline Version of the C-SSRS.
* Subjects currently in an acute relapse of schizophrenia as assessed by the investigator.
* Subjects with a current DSM-V diagnosis other than schizophrenia. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

Primary outcomes:
measure: Change in Suicidality via Columbia-Suicide Severity Rating Scale
timeFrame: Part A: Screening to Day 182; Part B: Screening to Day 126
measure: Number of reported Adverse Events (AE)
timeFrame: Part A: 182 days; Part B: 126 days
measure: Clinical Laboratory Tests
timeFrame: Part A: 182 days; Part B: 126 days
measure: Change in physical exam results
timeFrame: Part A: Screening to Day 182; Part B: Screening to Day 126
measure: Change in Systolic/Diastolic blood pressure from screening to end of study
timeFrame: Part A: Screening to Day 182; Part B: Screening to Day 126
measure: ECG Reading
timeFrame: Part A: 182 days; Part B: 126 days
measure: Extrapyramidal Symptoms (EPS) Rating Scale
timeFrame: Part A: 182 days; Part B: 126 days
measure: Investigator's assessment of injection site
timeFrame: Part A: 182 days; Part B: 126 days
measure: Visual analog scale (VAS) scores for pain reception
timeFrame: Part A: 182 days; Part B: 126 days
Secondary outcomes:
measure: Maximum peak plasma concentration (Cmax) [Pharmacokinetics]
timeFrame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
measure: Time of Cmax (tmax) [Pharmacokinetics]
timeFrame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
measure: Area under the concentration-time curve (AUC) from time zero to time "t" (Last observable concentration; AUCt) [Pharmacokinetics]
timeFrame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
measure: AUC from time zero to infinity (AUC∞) [Pharmacokinetics]
timeFrame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
measure: Terminal-phase elimination half-life (t1/2,z) [Pharmacokinetics]
timeFrame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
measure: Apparent clearance of drug from plasma after extravascular administration (CL/F; brexpiprazole only) [Pharmacokinetics]
timeFrame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuro Science (CNS)
state: California
city: San Diego
country: United States
facility: CNRI
state: California
Study officials:
References: