Safety and Tolerability Study of Single-dose Administration of Brexpiprazole in Adult Subjects With Schizophrenia

NCT02968121 | Terminated Phase 1

• 1 other identifier: 331-201-00033
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (9)

• Change in Suicidality via Columbia-Suicide Severity Rating Scale

  Baseline version and Since Last Visit version of CSSRS will be completed by trained trial center staff

  Part A: Screening to Day 182; Part B: Screening to Day 126

• Number of reported Adverse Events (AE)

  Part A: 182 days; Part B: 126 days

• Clinical Laboratory Tests

  Hematology, serum chemistry, urinalysis, drug screen, etc. will be performed.

  Part A: 182 days; Part B: 126 days

• Change in physical exam results

  Investigator or designee will perform complete physical exam and document any clinically significant conditions. Body height and weight will also be measured for BMI calculation and weight will be measured as part of all subsequent physical exams.

  Part A: Screening to Day 182; Part B: Screening to Day 126

• Change in Systolic/Diastolic blood pressure from screening to end of study

  Heart rate and body temperature will also be obtained prior to PK blood draws and ECG.

  Part A: Screening to Day 182; Part B: Screening to Day 126

• ECG Reading

  12-lead ECG will be collected in triplicate (5 minutes apart). heart rate, ventricular rate, RR interval, PR interval, QRS duration and QT intervals will be recorded. QTcF and corrected QT interval using Bazett's formula will be calculated.

  Part A: 182 days; Part B: 126 days

• Extrapyramidal Symptoms (EPS) Rating Scale

  SAS, AIMS \& BARS will be assess by trained trial center staff

  Part A: 182 days; Part B: 126 days

• Investigator's assessment of injection site

  Injection site will be assessed. Injection site will also be inspected for seepage after needle is withdrawn.

  Part A: 182 days; Part B: 126 days

• Visual analog scale (VAS) scores for pain reception

  Part A: 182 days; Part B: 126 days

Secondary Outcomes (6)

• Maximum peak plasma concentration (Cmax) [Pharmacokinetics]

  Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)

• Time of Cmax (tmax) [Pharmacokinetics]

  Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)

• Area under the concentration-time curve (AUC) from time zero to time "t" (Last observable concentration; AUCt) [Pharmacokinetics]

  Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)

• AUC from time zero to infinity (AUC∞) [Pharmacokinetics]

  Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)

• Terminal-phase elimination half-life (t1/2,z) [Pharmacokinetics]

  Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)

Study Arms (5)

Part A: Single Dose Injection: Subcutaneous

EXPERIMENTAL

Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous

Drug: Brexpiprazole, OPDC-34712

Part A: Single Dose Injection: Intramuscular

EXPERIMENTAL

Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous

Drug: Brexpiprazole, OPDC-34712

Part B: Cohort 1

EXPERIMENTAL

Drug: Brexpiprazole, OPDC-34712 Once, SC or IM

Drug: Brexpiprazole, OPDC-34712

Part B: Cohort 2

EXPERIMENTAL

Drug: Brexpiprazole, OPDC-34712 Once, SC or IM

Drug: Brexpiprazole, OPDC-34712

Part B: Cohort 3

EXPERIMENTAL

Drug: Brexpiprazole, OPDC-34712 Once, SC or IM

Drug: Brexpiprazole, OPDC-34712

Interventions

Brexpiprazole, OPDC-34712 DRUG

Part A: Single Dose Injection: Intramuscular; Part A: Single Dose Injection: Subcutaneous; Part B: Cohort 1; Part B: Cohort 2; Part B: Cohort 3

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (2)

Collaborative Neuro Science (CNS)

Garden Grove, California, 92845, United States

Location

CNRI

San Diego, California, 92102, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 18, 2016
• Study Start: January 1, 2017
• Primary Completion: December 14, 2017
• Study Completion: December 14, 2017
• Last Updated: January 12, 2018

Record last verified: 2018-01

Locations

US (2)