Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 and Aripiprazole for Treatment of Acute Schizophrenia (STEP 203)

A Phase 2, 6-Week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 Once Daily and Aripiprazole Once Daily for Treatment of Hospitalized Adult Patients With Acute Schizophrenia

This will be a multicenter, randomized, double-blind, placebo-controlled study designed to assess the tolerability, safety, and efficacy of OPC-34712 (0.25 to 6.0 mg) for the treatment of adult subjects hospitalized with an acute relapse of schizophrenia. Aripiprazole (10 to 20 mg) is included as a positive control to confirm the assay sensitivity of the study. A total of approximately 563 subjects will be screened at an estimated 75 sites worldwide in order to obtain approximately 450 randomized subjects.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: OPC-34712; Drug: Aripiprazole

• Study Type: Interventional
• Enrollment (Actual): 459
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Study Site
  • Kazanlak, Bulgaria, 6100
    • Study Site
  • Pazardzhik, Bulgaria, 4400
    • Study Site
  • Plovdiv, Bulgaria, 4002
    • Study Site
  • Radnevo, Bulgaria, 6260
    • Study Site
  • Ruse, Bulgaria, 7003
    • Study Site
• Croatia
  • Rijeka, Croatia, 51000
    • Study Site
  • Split, Croatia, 21000
    • Study Site
  • Zagreb, Croatia, 10090
    • Study Site
• India
  • Andh Prad
    • Vijaywada, Andh Prad, India, 520002
      • Study Site
    • Visakhapatnam, Andh Prad, India, 530017
      • Study Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380015
      • Study Site
  • Karna
    • Bangalore, Karna, India, 560010
      • Study Site
    • Mangalore, Karna, India, 575001
      • Study Site
    • Mangalore, Karna, India, 575018
      • Study Site
  • Mahara
    • Pune, Mahara, India, 411004
      • Study Site
  • Tamilnadu
    • Chennai, Tamilnadu, India, 600003
      • Study Site
  • Uttar Prad
    • Varanasi, Uttar Prad, India, 221005
      • Study Site
• Korea, Republic of
  • Busan, Korea, Republic of, 613-735
    • Study Site
  • Chuncheon, Korea, Republic of, 200-704
    • Study Site
  • Incheon, Korea, Republic of, 400-711
    • Study Site
  • Incheon, Korea, Republic of, 405-760
    • Study Site
  • Seoul, Korea, Republic of, 143-711
    • Study Site
• Philippines
  • Cebu City 6000, Philippines
    • Study Site
  • Mandaluyong City 1553, Philippines
    • Study Site
• Romania
  • Arad, Romania, 310022
    • Study Site
  • Bucuresti, Romania, 010825
    • Study Site
  • Bucuresti, Romania, 041914
    • Study Site (1)
  • Bucuresti, Romania, 041914
    • Study Site (2)
  • Bucuresti, Romania, 041914
    • Study Site (3)
  • Cluj-Napoca, Romania, 400012
    • Study Site
  • Oradea, Romania, 410154
    • Study Site
• Russian Federation
  • Moscow, Russian Federation, 113152
    • Study Site
  • Moscow, Russian Federation, 115522
    • Study Site
  • Moscow Region, Russian Federation, 141371
    • Study Site
  • St. Petersburg, Russian Federation, 190121
    • Study Site
  • St. Petersburg, Russian Federation, 193167
    • Study Site
  • St. Petersburg, Russian Federation, 197341
    • Study Site
• Serbia
  • Belgrade, Serbia, 11000
    • Study Site (1)
  • Belgrade, Serbia, 11000
    • Study Site (2)
  • Kragujevac, Serbia, 34000
    • Study Site
  • Novi Sad, Serbia, 21000
    • Study Site
• Slovakia
  • Bojnice, Slovakia, 92701
    • Study Site
  • Bratislava, Slovakia, 82606
    • Study Site
  • Liptovsky Mikulas, Slovakia, 03123
    • Study Site
  • Rimavska Sobota, Slovakia, 97912
    • Study Site
  • Zilina, Slovakia, 01207
    • Study Site
• Taiwan
  • Hualien Town, Taiwan, 970
    • Study Site
  • Taipei, Taiwan, 249
    • Study Site
• Ukraine
  • Chernigiv, Ukraine, 14005
    • Study Site
  • Dnipropetrovsk, Ukraine, 49005
    • Study Site
  • Kherson,Vil. Stepanivka, Ukraine, 73488
    • Study Site
  • Kyiv, Ukraine, 02660
    • Study Site
  • Kyiv, Ukraine, 04080
    • Study Site
  • Kyiv, Ukraine, 04655
    • Study Site
  • Simferopol, Ukraine, 95006
    • Study Site
  • Vinnitsia, Ukraine, 21018
    • Study Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Study Site
  • California
    • Escondido, California, United States, 92025
      • Study Site
    • Garden Grove, California, United States, 92645
      • Study Site
    • Long Beach, California, United States, 90813
      • Study Site
    • Oceanside, California, United States, 92056
      • Study Site
    • Pasadena, California, United States, 91107
      • Study Site
    • San Diego, California, United States, 92123
      • Study Site
    • San Diego, California, United States, 92102
      • Study Site
    • Santa Ana, California, United States, 92701
      • Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Study Site
  • Florida
    • Bradenton, Florida, United States, 34208
      • Study Site
    • Maitland, Florida, United States, 32751
      • Study Site
  • Missouri
    • St. Louis, Missouri, United States, 63118
      • Study Site
  • New York
    • Cedarhurst, New York, United States, 11516
      • Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • Study Site
  • Texas
    • Austin, Texas, United States, 78756
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects between 18 and 65 years of age, with a diagnosis of schizophrenia, as defined by DSM-IV-TR criteria
2. Subjects who have been recently hospitalized or who would benefit from hospitalization for an acute relapse of schizophrenia
3. Subjects experiencing an acute exacerbation of psychotic symptoms

Exclusion Criteria:

1. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug

2. Subjects with a current DSM-IV-TR Axis I diagnosis of:

   • Schizoaffective disorder
   • MDD
   • Bipolar disorder
   • Delirium, dementia, amnestic or other cognitive disorder
   • Borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder
3. Subjects presenting with a first episode of schizophrenia
4. Other protocol specific inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 5	Drug: Placebo; Placebo
EXPERIMENTAL: 1; OPC-34712 0.25 mg arm	Drug: OPC-34712; oral, once daily
EXPERIMENTAL: 2; OPC-34712 low-dose arm	Drug: OPC-34712; oral, once daily
EXPERIMENTAL: 3; OPC-34712 mid-dose arm	Drug: OPC-34712; oral, once daily
EXPERIMENTAL: 4; OPC-34712 high-dose arm	Drug: OPC-34712; oral, once daily
ACTIVE_COMPARATOR: 6; Aripiprazole arm	Drug: Aripiprazole; oral, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase)	The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS total score is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase)	The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms.	Baseline to Week 6
Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase)	The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. PANSS negative subscale score is the sum of the rating scores for the 7 negative scale items from the PANSS panel. The PANSS negative subscale score ranges from 7-49, with higher scores indicating more severe symptoms.	Baseline to Week 6
Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase)	The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains. The rating is based on four main areas: (a) socially useful activities, including work and study; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The ratings are converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Ratings from 71-100 reflect only mild difficulties. Ratings from 31-70 reflect manifest disabilities of various degrees. Ratings from 1-30 reflect functioning so poor that intensive support or supervision is needed.	Baseline to Week 6
Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase)	The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices include the following: 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients	Baseline to Week 6
Mean Clinical Global Impression - Improvement (CGI-I) at Week 6	The rater or investigator rated the particpant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at baseline prior to the first dose of double-blind study medication. Response choices included the following: 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.	Week 6
Response Rate at Week 6	Response rate was defined as a reduction of ≥ 30% from baseline in PANSS Total Score; or a CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6	Week 6
Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712	Efficacy-related discontinuation rate was assessed	Baseline to Week 6

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Kane JM, Skuban A, Hobart M, Ouyang J, Weiller E, Weiss C, Correll CU. Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia. Schizophr Res. 2016 Jul;174(1-3):93-98. doi: 10.1016/j.schres.2016.04.013. Epub 2016 May 14.
• Citrome L. Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2015 Sep;69(9):978-97. doi: 10.1111/ijcp.12714. Epub 2015 Aug 6.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ACTUAL): September 1, 2010
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: May 19, 2009
• First Submitted That Met QC Criteria: May 19, 2009
• First Posted (ESTIMATE): May 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 20, 2015
• Last Update Submitted That Met QC Criteria: September 29, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Schizophrenia; Relapsed
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 331-07-203