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Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia (Anew)

Primary Purpose

Treatment-resistant Schizophrenia

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Lu AF35700
Risperidone
Olanzapine
Sponsored by
H. Lundbeck A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment-resistant Schizophrenia focused on measuring Treatment-resistant schizophrenia, Lu AF35700

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • The patient has schizophrenia, diagnosed according to DSM-5(TM). (Diagnostic and Statistical Manual of Mental Disorders) and confirmed by the Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI-Schz).
  • The patient is receiving treatment with a psychiatrist in either an inpatient or outpatient facility.
  • The patient has been treated with adequate dose(s) of antipsychotic drug treatment for at least 2 weeks prior to the Screening Visit.
  • The patient has failed to show an adequate response in the level of psychotic symptoms during at least one documented treatment trial with an adequate dose of an antipsychotic drug prescribed for an adequate time (at least lasting for 6 weeks) within 2 years prior to the Screening Visit. The failure to respond to the current antipsychotic drug treatment trial may be considered a retrospective failed treatment, if the patient has been treated for 6 weeks with adequate dose(s) of antipsychotic drug(s).
  • The patient has a PANSS total score of ≥80 (on 1-7 scale) and a score of ≥4 (≥ "Moderate" on 1-7 scale) on at least 2 of the following PANSS items at the Screening and at Baseline 1 [Week 0] Visits: P2 - Conceptual disorganization, P3 - Hallucinatory behavior, P6 - Suspiciousness/persecution, G9 - Unusual thought content; AND the patient has a CGI-S score of ≥4 (≥ "Moderately ill") at the Screening and at Baseline 1 (Week 0) Visits.

Exclusion Criteria:

  • The patient has any current primary psychiatric disorder other than schizophrenia, as assessed using the MINI-Schz.
  • The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria).
  • The patient is experiencing an acute exacerbation of his/her psychotic symptoms.
  • The patient has been treated with, AND is resistant to, clozapine according to the investigator's judgement.

Sites / Locations

  • University of California San Diego Health System
  • Emory University Cognitive Neurology Clinic & ADRC
  • Northwestern University
  • Corrigan Mental Health Center
  • University Of Massachusetts Medical Center
  • Michigan Clinical Research Institute PC
  • Kalamazoo Community Mental Health and Substance Abuse Services
  • PsychCare Consultants Research
  • Creighton University
  • Psychiatric and Behavioral Solutions
  • SPH - Kardzhali
  • State Psychiatric Hospital
  • UMHAT
  • State Psychiatric Hospital
  • DCC St. Vrach and St.St. Kuzma and Damian
  • MHC - Sofia
  • MHAT - Targovishte
  • Takeda General Hospital - JP0009
  • Takeda General Hospital
  • Kohnodai Hospital
  • Nara Medical University Hospital
  • University of Occupational and Environmental Health Hospital
  • Sankeikai Nishigahara Hospital - JP0008
  • National Center of Neurology and Psychiatry
  • Satokai Yuge Hospital
  • NHO Ryukyu Hospital
  • Fujita Health University Hospital
  • Sverdlovsk Regional Clinical Psychiatric Hospital
  • GUZ Lipetsk Regional psychoneurological Hospital 1
  • Lipetsk Regional Psychoneurological Hospital
  • City Psychiatric Hospital # 6
  • Psychoneurological Dispensary #10
  • Psychoneurological Dispensary #1
  • Samara Psychiatric Hospital
  • Tomsk National Research Medical Centre of the Russian Academy of Sciences
  • Yaroslavl Regional Clinical Psychiatric Hospital
  • Royal Edinburgh Hospital
  • The Maudsley Hospital - GB0001
  • The Maudsley Hospital
  • Manchester Mental Health & Social Care NHS Trust - GB0003
  • Manchester Mental Health & Social Care NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Prospective Confirmation (PC) Period

Double-blind treatment (DBT) period, Lu AF35700 10 mg

DBT Period, Continued treatment from PC Period

Arm Description

Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks

Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks

Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period

Outcomes

Primary Outcome Measures

Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.

Secondary Outcome Measures

Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score
CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening
Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score
The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.
Change From Randomization to Week 8 in PANSS Marder Negative Factor Score
The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.
Response
Response is defined as a ≥20% reduction in PANSS total score from Randomization

Full Information

First Posted
July 24, 2017
Last Updated
January 10, 2020
Sponsor
H. Lundbeck A/S
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1. Study Identification

Unique Protocol Identification Number
NCT03230864
Brief Title
Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia
Acronym
Anew
Official Title
Interventional, Randomized, Double-blind, Active-controlled Study of the Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
New data; the study was terminated based on new efficacy data from another study
Study Start Date
July 20, 2017 (Actual)
Primary Completion Date
December 23, 2018 (Actual)
Study Completion Date
February 5, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lundbeck A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia (TRS)
Detailed Description
In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective confirmation (PC) period. The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks), a Double-blind Treatment (DBT) Period (8 weeks), and a Safety Follow-up Period (6 weeks). Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period. Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT period and were randomized into one of the 2 treatmetn arms (1:1) with either Lu AF35700 10 mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the dose set at the last visit of the PC period. This means that approximately half of the confirmed treatment-resistant patients were randomised back to the failed treatment in the PC period. Data was not collected seperately for the DBT olanzapine and DBT risperidone participants, and there was no intent to compare Lu AF35700 to each drug seperately.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment-resistant Schizophrenia
Keywords
Treatment-resistant schizophrenia, Lu AF35700

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prospective Confirmation (PC) Period
Arm Type
Experimental
Arm Description
Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks
Arm Title
Double-blind treatment (DBT) period, Lu AF35700 10 mg
Arm Type
Experimental
Arm Description
Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks
Arm Title
DBT Period, Continued treatment from PC Period
Arm Type
Experimental
Arm Description
Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period
Intervention Type
Drug
Intervention Name(s)
Lu AF35700
Intervention Description
10 mg/day, encapsulated tablets, orally
Intervention Type
Drug
Intervention Name(s)
Risperidone
Intervention Description
4-6 mg/day, encapsulated tablets, orally
Intervention Type
Drug
Intervention Name(s)
Olanzapine
Intervention Description
15-20 mg/day, encapsulated tablets, orally
Primary Outcome Measure Information:
Title
Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
Description
PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.
Time Frame
From Randomization to Week 8
Secondary Outcome Measure Information:
Title
Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score
Description
CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening
Time Frame
From Randomization to Week 8
Title
Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score
Description
The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.
Time Frame
From Randomization to Week 8
Title
Change From Randomization to Week 8 in PANSS Marder Negative Factor Score
Description
The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.
Time Frame
From Randomization to Week 8
Title
Response
Description
Response is defined as a ≥20% reduction in PANSS total score from Randomization
Time Frame
at Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient has schizophrenia, diagnosed according to DSM-5(TM). (Diagnostic and Statistical Manual of Mental Disorders) and confirmed by the Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI-Schz). The patient is receiving treatment with a psychiatrist in either an inpatient or outpatient facility. The patient has been treated with adequate dose(s) of antipsychotic drug treatment for at least 2 weeks prior to the Screening Visit. The patient has failed to show an adequate response in the level of psychotic symptoms during at least one documented treatment trial with an adequate dose of an antipsychotic drug prescribed for an adequate time (at least lasting for 6 weeks) within 2 years prior to the Screening Visit. The failure to respond to the current antipsychotic drug treatment trial may be considered a retrospective failed treatment, if the patient has been treated for 6 weeks with adequate dose(s) of antipsychotic drug(s). The patient has a PANSS total score of ≥80 (on 1-7 scale) and a score of ≥4 (≥ "Moderate" on 1-7 scale) on at least 2 of the following PANSS items at the Screening and at Baseline 1 [Week 0] Visits: P2 - Conceptual disorganization, P3 - Hallucinatory behavior, P6 - Suspiciousness/persecution, G9 - Unusual thought content; AND the patient has a CGI-S score of ≥4 (≥ "Moderately ill") at the Screening and at Baseline 1 (Week 0) Visits. Exclusion Criteria: The patient has any current primary psychiatric disorder other than schizophrenia, as assessed using the MINI-Schz. The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria). The patient is experiencing an acute exacerbation of his/her psychotic symptoms. The patient has been treated with, AND is resistant to, clozapine according to the investigator's judgement.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Email contact via H.Lundbeck A/S
Organizational Affiliation
LundbeckClinicalTrials@Lundbeck.com
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego Health System
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Emory University Cognitive Neurology Clinic & ADRC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Corrigan Mental Health Center
City
Fall River
State/Province
Massachusetts
ZIP/Postal Code
02720
Country
United States
Facility Name
University Of Massachusetts Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605-2610
Country
United States
Facility Name
Michigan Clinical Research Institute PC
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48108
Country
United States
Facility Name
Kalamazoo Community Mental Health and Substance Abuse Services
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49001
Country
United States
Facility Name
PsychCare Consultants Research
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63128
Country
United States
Facility Name
Creighton University
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Psychiatric and Behavioral Solutions
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84105
Country
United States
Facility Name
SPH - Kardzhali
City
Kardzhali
Country
Bulgaria
Facility Name
State Psychiatric Hospital
City
Novi Iskar
Country
Bulgaria
Facility Name
UMHAT
City
Pleven
Country
Bulgaria
Facility Name
State Psychiatric Hospital
City
Radnevo
Country
Bulgaria
Facility Name
DCC St. Vrach and St.St. Kuzma and Damian
City
Sofia
Country
Bulgaria
Facility Name
MHC - Sofia
City
Sofia
Country
Bulgaria
Facility Name
MHAT - Targovishte
City
Tărgovište
Country
Bulgaria
Facility Name
Takeda General Hospital - JP0009
City
Aizu-Wakamatsu
Country
Japan
Facility Name
Takeda General Hospital
City
Fukushima
Country
Japan
Facility Name
Kohnodai Hospital
City
Ichikawa
Country
Japan
Facility Name
Nara Medical University Hospital
City
Kashihara
Country
Japan
Facility Name
University of Occupational and Environmental Health Hospital
City
Kitakyushu
Country
Japan
Facility Name
Sankeikai Nishigahara Hospital - JP0008
City
Kita
Country
Japan
Facility Name
National Center of Neurology and Psychiatry
City
Kodaira
Country
Japan
Facility Name
Satokai Yuge Hospital
City
Kumamoto
Country
Japan
Facility Name
NHO Ryukyu Hospital
City
Kunigami
Country
Japan
Facility Name
Fujita Health University Hospital
City
Toyoake
Country
Japan
Facility Name
Sverdlovsk Regional Clinical Psychiatric Hospital
City
Ekaterinburg
Country
Russian Federation
Facility Name
GUZ Lipetsk Regional psychoneurological Hospital 1
City
Lipetsk
Country
Russian Federation
Facility Name
Lipetsk Regional Psychoneurological Hospital
City
Lipetsk
Country
Russian Federation
Facility Name
City Psychiatric Hospital # 6
City
Saint Petersburg
Country
Russian Federation
Facility Name
Psychoneurological Dispensary #10
City
Saint Petersburg
Country
Russian Federation
Facility Name
Psychoneurological Dispensary #1
City
Saint Petersburg
Country
Russian Federation
Facility Name
Samara Psychiatric Hospital
City
Samara
Country
Russian Federation
Facility Name
Tomsk National Research Medical Centre of the Russian Academy of Sciences
City
Tomsk
Country
Russian Federation
Facility Name
Yaroslavl Regional Clinical Psychiatric Hospital
City
Yaroslavl
Country
Russian Federation
Facility Name
Royal Edinburgh Hospital
City
Edinburgh
Country
United Kingdom
Facility Name
The Maudsley Hospital - GB0001
City
London
Country
United Kingdom
Facility Name
The Maudsley Hospital
City
London
Country
United Kingdom
Facility Name
Manchester Mental Health & Social Care NHS Trust - GB0003
City
Manchester
Country
United Kingdom
Facility Name
Manchester Mental Health & Social Care NHS Trust
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia

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