Multicenter, Open-label, Safety and Tolerability Study

Schizophrenia Clinical Trial

— STEP 210  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01649557
• Other study ID #: 331-08-210
• Status: Completed
• Phase: Phase 2
• First received: July 20, 2012
• Last updated: September 29, 2015
• Start date: August 2009
• Est. completion date: September 2011

Study information

• Verified date: September 2015
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: September 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 67 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Outpatient status at last visit of Study 331-07-203.

Exclusion Criteria:

1. 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.

2. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving open-label OPC-34712.

3. 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.

4. 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.

5. 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.

6. Subjects who would be likely to require prohibited concomitant therapy during the study.

7. Any subject who, in the opinion of the investigator, should not participate in the study.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• OPC-34712
oral administered once daily

Locations

Country	Name	City	State
Bulgaria	Otsuka Investigational Site	Burgas
Bulgaria	Otsuka Investigational Site	Kazanlak
Bulgaria	Otsuka Investigational Site	Pazardzhik
Bulgaria	Otsuka Investigational Site	Plovdiv
Bulgaria	Otsuka Investigational Site	Radnevo
Bulgaria	Otsuka Investigational Site	Ruse
Croatia	Otsuka Investigational Site	Rijeka
Croatia	Otsuka Investigational Site	Zagreb
India	Otsuka Investigational Site	Ahmedabad	Gujarat
India	Otsuka Investigational Site	Bangalore	Karna
India	Otsuka Investigational Site	Chennai	Tamilnadu
India	Otsuka Investigational Site	Mangalore	Karna
India	Otsuka Investigational Site	Mangalore	Karna
India	Otsuka Investigational Site	Pune	Mahara
India	Otsuka Investigational Site	Varanasi	Uttar Prad
India	Otsuka Investigational Site	Vijaywada	Andh Prad
India	Otsuka Investigational Site	Visakhapatnam	Andh Prad
Korea, Republic of	Otsuka Investigational Site	Chuncheon
Korea, Republic of	Otsuka Investigational Site	Incheon
Korea, Republic of	Otsuka Investigational Site	Incheon
Korea, Republic of	Otsuka Investigational Site	Seoul
Philippines	Otsuka Investigational Site	Cebu City
Philippines	Otsuka Investigational Site	Mandaluyong City
Romania	Otsuka Investigational Site	Arad
Romania	Otsuka Investigational Site	Bucuresti
Romania	Otsuka Investigational Site	Bucuresti
Romania	Otsuka Investigational Site	Bucuresti 2
Romania	Otsuka Investigational Site	Bucuresti 3
Romania	Otsuka Investigational Site	Cluj - Napoca
Romania	Otsuka Investigational Site	Oradea
Russian Federation	Otsuka Investigational Site	Moscow
Russian Federation	Otsuka Investigational Site	Moscow Region
Russian Federation	Otsuka Investigational Site	St. Petersburg
Russian Federation	Otsuka Investigational Site	St. Petersburg
Russian Federation	Otsuka Investigational Site	St. Petersburg
Russian Federation	Otsuka Investigational Site	Zagorodnoye
Serbia	Otsuka Investigational Site	Belgrade
Serbia	Otsuka Investigational Site	Belgrade 2
Serbia	Otsuka Investigational Site	Kragujevac
Serbia	Otsuka Investigational Site	NoviSad
Slovakia	Otsuka Investigational Site	Bojnice
Slovakia	Otsuka Investigational Site	Bratislava
Slovakia	Otsuka Investigational Site	Liptovsky Mikulas
Slovakia	Otsuka Investigational Site	Rimavska Sobota
Slovakia	Otsuka Investigational Site	Zilina
Taiwan	Otsuka Investigational Site	Hualian
Taiwan	Otsuka Investigational Site	Taipei
Ukraine	Otsuka Investigational Site	Chernigiv
Ukraine	Otsuka Investigational Site	Dnipropetrovsk
Ukraine	Otsuka Investigational Site	Kyiv
Ukraine	Otsuka Investigational Site	Kyiv
Ukraine	Otsuka Investigational Site	Kyiv
Ukraine	Otsuka Investigational Site	Simferopol
Ukraine	Otsuka Investigational Site	Stepanivka
Ukraine	Otsuka Investigational Site	Vinnytsya
United States	Otsuka Investigational Site	Austin	Texas
United States	Otsuka Investigational Site	Bradenton	Florida
United States	Otsuka Investigational Site	Cedarhurst	New York
United States	Otsuka Investigational Site	Escondido	California
United States	Otsuka Investigational Site	Garden Grove	California
United States	Otsuka Investigational Site	Little Rock	Arkansas
United States	Otsuka Investigational Site	Long Beach	California
United States	Otsuka Investigational Site	Maitland	Florida
United States	Otsuka Investigational Site	Oceanside	California
United States	Otsuka Investigational Site	Pasadena	California
United States	Otsuka Investigational Site	Philadelphia	Pennsylvania
United States	Otsuka Investigational Site	San Diego	California
United States	Otsuka Investigational Site	San Diego	California
United States	Otsuka Investigational Site	Santa Ana	California
United States	Otsuka Investigational Site	St. Louis	Missouri
United States	Otsuka Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  India,  Korea, Republic of,  Philippines,  Romania,  Russian Federation,  Serbia,  Slovakia,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No