SchizophreniaPhase 4HDLNCT01569659
High Dose Lurasidone for Patients With Treatment Resistant Schizophrenia
A Phase 4 study testing Lurasidone in people with Schizophrenia, run by Northwestern University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Lurasidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2011to Jul 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 15Show fewer
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University Department of Psychiatry and Behavioral Sciences
Chicago, Illinois, 60611
Northwestern University Psychiatric Clinical Research Program
Chicago, Illinois, 60611
About this study
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- Lurasidone
- Keywords
- Schizophrenia, Refractory, Treatment resistant, Lurasidone
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LurasidoneDrug
Also called Latuda
80 mg/day for up to 30 weeks
LurasidoneDrug
Also called Latuda
Up to 240 mg/day for up to 30 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Lurasidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to end of randomized phase (24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2012 (estimated)
- Study startOct 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Sumitomo Pharma America, Inc.
- Responsible party
- Sponsor
- Investigators
- Herbert Meltzer, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01569659
- Sponsor's protocol ID
- Sunovion Pharmaceuticals
- Acronym
- HDL
- Status last verified
- Feb 2025
- First submitted
- 29 Mar 2012
- Last updated
- 28 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 31706786
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose Lurasidone for Patients With Treatment Resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT01569659
- Acronym / sponsor ID
- HDL / Sunovion Pharmaceuticals
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Refractory, Treatment resistant, Lurasidone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Sumitomo Pharma America, Inc.
- Study start
- Oct 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 3 Apr 2012 (estimated)
- Results
- Posted 28 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard dose of lurasidone | Active comparator | Drug: LurasidoneOnly 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. |
| High dose of lurasidone | Experimental | Drug: LurasidoneIn 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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:
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LurasidoneAlso: Latuda80 mg/day for up to 30 weeks | Drug | Standard dose of lurasidone |
| LurasidoneAlso: LatudaUp to 240 mg/day for up to 30 weeks | Drug | High dose of lurasidone |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31706786Karpouzian-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Herbert Meltzer, MD principal investigator
Northwestern University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lurasidone in people with Schizophrenia, run by Northwestern University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Positive Symptoms of Schizophrenia (time frame: Baseline to end of randomized phase (24 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01569659, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.