High Dose Lurasidone for Patients With Treatment Resistant Schizophrenia (HDL)

February 24, 2025 updated by: Northwestern University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to conduct a double-blind, randomized trial of lurasidone (80 mg vs 160-240 mg/day) after a 6 week trial of 80 mg/day (phase 1), in treatment resistant adult patients. 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 and 40 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. No additional antipsychotic drug of any kind will be permitted in either group during Phase II. Because they are treatment resistant, patients who are doing poorly in either of the two groups in phase II as indicated by level of psychopathology, or as tolerated, and who the clinicians at any site feel should no longer receive lurasidone, will be dropped, and would ordinarily be considered for treatment with clozapine. Where possible, another assessment of these patients, two weeks and four weeks after completion of the trial or early termination will be conducted.

All subjects who enter the phase 1 study will be consented to obtain a blood sample for genetic studies to search for possible markers for response to lurasidone and treatment resistant schizophrenia. DNA from non-treatment resistant patients already studied by the PI will be available for comparison. Following the completion of the study, the PI and the sponsor will discuss how best to analyze the DNA obtained and a separate contract will be written, if indicated.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Department of Psychiatry and Behavioral Sciences
      • Chicago, Illinois, United States, 60611
        • Northwestern University Psychiatric Clinical Research Program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    • failure to respond adequately to two or more trials with typical or atypical antipsychotic drugs, of adequate dose and duration (at least 6 weeks) lifetime and at least one such trial within the last two years. No patient with a history of a successful trial of this nature within the last two years will be eligible for inclusion. The minimum doses of antipsychotic drugs permitted in these unsuccessful trials are specified in Table 1.
    • 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard dose of lurasidone
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
80 mg/day for up to 30 weeks
Other Names:
  • Latuda
Drug: Lurasidone
Up to 240 mg/day for up to 30 weeks
Other Names:
  • Latuda
Experimental: High dose of lurasidone
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
80 mg/day for up to 30 weeks
Other Names:
  • Latuda
Drug: Lurasidone
Up to 240 mg/day for up to 30 weeks
Other Names:
  • Latuda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Positive Symptoms of Schizophrenia
Time Frame: Baseline to end of randomized phase (24 weeks)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Sumitomo Pharma America, Inc.

Investigators

  • Principal Investigator: Herbert Meltzer, MD, Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

March 29, 2012

First Submitted That Met QC Criteria

April 2, 2012

First Posted (Estimated)

April 3, 2012

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 24, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sunovion Pharmaceuticals

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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