Multicenter, Open-label, Safety and Tolerability Study

Study Overview
=================
Brief Summary
-----------------
This will be a multicenter, 52 week, open label study to assess the safety and tolerability of oral OPC-34712 (1 to 6 mg) as monotherapy in adult patients with schizophrenia. The study will be conducted on an outpatient basis. Enrollment into the study will be drawn from eligible subjects who have completed participation in Study 331-07- 203 and who, in the investigator's judgment, would benefit from continued treatment with oral OPC-34712.

Official Title
-----------------
A Phase 2, Multicenter, Open-label Study to Assess the Safety and Tolerability of Oral OPC-34712 as Monotherapy in Adult Patients With Schizophrenia

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: OPC-34712


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who participated in 331-07-203 and who, in the opinion of the investigator, have the potential to benefit from continued administration of OPC-34712 for the treatment of schizophrenia. Outpatient status at last visit of Study 331-07-203. Exclusion Criteria: Sexually active males who are not practicing two different methods of birth control during the study and for 90 days after the last dose of study medication or who will not remain abstinent during the study and for 90 days after the last dose, or sexually active females of childbearing potential who are not practicing two different methods of birth control during the study and for 30 days after the last dose of study medication or who will not remain abstinent during the study and for 30 days after the last dose. If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injection, birth control implant, condom, or sponge with spermicide. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving open-label OPC-34712. Subjects who during the course of their participation in 331-07-203 were treated in violation of the protocol or who developed ANY exclusion criteria during the course of their participation. Subjects who do not continue to meet all applicable inclusion/exclusion criteria for Protocol 331-07-203 at the last visit (ie, Week 6) of Protocol 331-07-203. Subjects who represent a risk of committing suicide based on an answer of Yes to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the Suicidal Ideation portion of the C-SSRS, or an answer of Yes to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior) on the Suicidal Behavior portion of the C-SSRS. A subject who has had any suicidal ideation within the last 6 months, any suicidal behaviors within the last two years, or who in the clinical judgment of the investigator presents a serious risk of suicide should be excluded from the study. Subjects who would be likely to require prohibited concomitant therapy during the study. Any subject who, in the opinion of the investigator, should not participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label OPDC-34712<br> | Drug: OPC-34712<br>* oral administered once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) During First 6 Weeks. | AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication. | From Baseline up to 6 weeks | 
| Number of Participants With AEs in 52-Week Enrollers. | AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A SAE was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A TEAE was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication. | From Baseline up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms. | Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit | 
| Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. | The severity of illness for each participant were rated using the CGI-S. To perform this assessment, the investigator were to answer the following question: Considering your total clinical experience with this particular population, how mentally ill was the participant at that time? Response choices include: 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; and 7 = among the most extremely ill participants. | Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit | 
| Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. | The PSP was a validated clinician-rated scale that measured personal and social functioning in four domains: socially useful activities (e.g, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then 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 that determined the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented manifest disabilities of various degrees and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision. | Baseline, Week 1, 2, 6, 26, 52 and Last Visit | 
| Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. | The efficacy of study medication was rated for each participant using the CGI-I. The investigator rated the participants total improvement whether or not it was due to the drug treatment. All responses were compared to the participants condition at Screening/Baseline (i.e, Week 6 visit of Protocol NCT00905307). Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit | 
| Change From Baseline in PANSS Positive Subscale Score. | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive symptom score ranges from 7-49, with higher scores indicating more severe symptoms. | Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit | 
| Change From Baseline in PANSS Negative Subscale Score. | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In negative subscale the severity was rated for the following 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. The PANSS negative symptom score ranges from 7-49, with higher scores indicating more severe symptoms. | Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit | 
| Percentage of Participants With a Positive Response Rate. | Response rate was defined as a reduction of ≥ 30% from Baseline in PANSS total score or CGI-I score of 1 (very much improved) or 2 (much improved) at the Last Visit. | Last Visit | 
| Percentage of Participants Who Discontinued Due to Lack of Efficacy. | Discontinuation rate for the participants discontinued due to lack of efficacy were examined. | Last Visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia