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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00905307
First received: May 19, 2009
Last updated: September 29, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Schizophrenia
Drug: OPC-34712
Drug: Placebo
Drug: Aripiprazole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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

  • Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    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.

  • Response Rate at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    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

  • Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    Efficacy-related discontinuation rate was assessed


Enrollment: 459
Study Start Date: July 2009
Study Completion Date: November 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: 5 Drug: Placebo
Placebo
Active Comparator: 6
Aripiprazole arm
Drug: Aripiprazole
oral, once daily

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00905307

  Show 73 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00905307     History of Changes
Other Study ID Numbers: 331-07-203 
Study First Received: May 19, 2009
Results First Received: August 4, 2015
Last Updated: September 29, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Schizophrenia
Relapsed

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Aripiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs

ClinicalTrials.gov processed this record on December 05, 2016