High Dose Lurasidone for Patients With Treatment Resistant Schizophrenia

NCT01569659 | Completed Phase 4 Results

• 1 other identifier: Sunovion Pharmaceuticals
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this study is to compare the efficacy of a flexible high dose of lurasidone to a standard dose of lurasidone in patients with treatment resistant schizophrenia or schizoaffective disorder. Efficacy of both dosage groups will be measured through testing of positive symptoms and other components of psychopathology (negative symptoms, general psychopathology, anxiety, depression, cognitive function, global function, severity of illness and tolerability). Patients must qualify for treatment resistance after two or more antipsychotic drug trials to be included in this trial.

Conditions

Schizophrenia

Keywords

Schizophrenia; Refractory; Treatment resistant; Lurasidone

Outcome Measures

Primary Outcomes (1)

• Change in Positive Symptoms of Schizophrenia

  Specify Full Scale Name and Construct: Positive and Negative Symptom Scale (PANSS) Scale description: A 45-minute clinical interview is conducted. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. These 30 items are split into three categories (Positive, Negative and General Psychopathology symptoms of schizophrenia), and the information is used to evaluate the presence, absence and severity of each. A score of 1 on an item indicates the absence of the symptom, up to a 7 which indicates the presence of the symptom is extreme. The minimum and maximum for the whole scale would be 30-210, and for each of the three categories are as follows: Positive scale (7 Items)--minimum score = 7, maximum score = 49; Negative scale (7 Items)--minimum score = 7, maximum score = 49; General Psychopathology scale (16 Items)--minimum score = 16, maximum score = 112.

  Baseline to end of randomized phase (24 weeks)

Study Arms (2)

Standard dose of lurasidone

ACTIVE COMPARATOR

Only those patients who still have persistent moderate to severe positive symptoms, even if they have shown some improvement at 80 mg/day will proceed to phase II (randomization). In phase II, 30 subjects will be randomized to continue 80 mg lurasidone.

Drug: Lurasidone

High dose of lurasidone

EXPERIMENTAL

In phase II, 40 patients will initiate a titration schedule, beginning at 120 mg at week 7. The high-dose group will be increased an additional 40 mg/day every week, thereafter, to a total of 240 mg/day, if adequately tolerated, which would include a worsening of psychopathology as assessed by the PANSS or CGI-S. The dose will remain at 240/day, or the highest dose tolerated, for a duration of 6 months from the time the 120 mg/day dose was initiated.

Drug: Lurasidone

Interventions

Lurasidone DRUG

80 mg/day for up to 30 weeks

Also known as: Latuda

Standard dose of lurasidone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients diagnosed with schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual IV (DSM-IV) criteria
• All patients must be capable of giving written informed consent.
• The criteria for treatment resistance (TR) will be those of Kane et al, (1988) which are:
• Patients must have scores of 4 (using a 1-7 scale) or more on at least two of the following Positive and Negative Syndrome Scale (PANSS) items: delusions \[P1\], hallucinations \[P3\] or unusual thought content \[G9\]
• Patients must have a total PANSS score of 70 or above
• Patients will have had no episodes of good functioning in the previous three years (as defined by current CGI - Severity of moderate to severe, Global Assessment of Functioning (GAF) below 60;
• Personal and Social Performance Scale of 60 or below.
• Requirement for previous exposure to antipsychotic treatment:
• Patients who meet treatment resistance criteria must have had at least two trials with approved antipsychotic drugs, typical or atypical, in the standard dose range. It is recognized that some treatment resistant patients will have had good responses to antipsychotic drugs before meeting treatment resistant criteria.
• All patients must have a Clinical Global Impression - Severity (CGI-S) scale score at screening of at least moderate severity, and must have a Personal and Social Performance (PSP) score of 60 or below.
• Patients may initially be inpatients or outpatients.
• Females of child bearing potential will be admitted only if they are on stable birth control medication and understand that they should not get pregnant during the course of the study. Pregnancy tests will be done at baseline and at approximately 2 month intervals.
• All patients must have stable housing at the current time or will be discharged to a stable outpatient setting for housing, if an inpatient.
• Patients must be willing to remain compliant on oral medication throughout the duration of the trial.

You may not qualify if:

• Patients unable to provide written, informed consent
• Patients with a diagnosis other than schizophrenia or schizoaffective disorder.
• Patients currently taking clozapine or have failed an adequate trial of clozapine which lasted at least 2 months.
• Patients who have already failed trials with high doses of other atypical antipsychotic drugs such as risperidone or olanzapine..
• Pregnant females and females who are currently breastfeeding will be excluded.
• Patients with a diagnosis of substance dependence at screening or up to one year prior to enrollment.
• Patients with a history of non-compliance to oral medication to a degree that would interfere with the determination of treatment resistance or diminish likelihood of complying with this protocol
• Patients \> age 60
• Uncontrolled medical conditions or recent myocardial infarction or stroke
• BMI =/\>45

Sponsors & Collaborators

• Northwestern University: lead
• Sumitomo Pharma America, Inc.: collaborator

Study Sites (2)

Northwestern University Department of Psychiatry and Behavioral Sciences

Chicago, Illinois, 60611, United States

Location

Northwestern University Psychiatric Clinical Research Program

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Karpouzian-Rogers T, Stocks J, Meltzer HY, Reilly JL. The effect of high vs. low dose lurasidone on eye movement biomarkers of prefrontal abilities in treatment-resistant schizophrenia. Schizophr Res. 2020 Jan;215:314-321. doi: 10.1016/j.schres.2019.10.008. Epub 2019 Nov 6.

  PMID: 31706786 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Lurasidone Hydrochloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Herbert Meltzer, MD
• Organization: Northwestern University

h-meltzer@northwestern.edu

312-503-9096

Study Officials

• Herbert Meltzer, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 3, 2012
• Study Start: October 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 28, 2025
• Results First Posted: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)