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

NCT03230864 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: 17303A
• Study Type: interventional
• Target: 119
• Locations: 5 countries
• Sites: 41

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)

Conditions

Treatment-resistant Schizophrenia

Keywords

Treatment-resistant schizophrenia; Lu AF35700

Outcome Measures

Primary Outcomes (1)

• 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.

  From Randomization to Week 8

Secondary Outcomes (4)

• Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score

  From Randomization to Week 8

• Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score

  From Randomization to Week 8

• Change From Randomization to Week 8 in PANSS Marder Negative Factor Score

  From Randomization to Week 8

• Response

  at Week 8

Study Arms (3)

Prospective Confirmation (PC) Period

EXPERIMENTAL

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

Drug: Risperidone; Drug: Olanzapine

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

EXPERIMENTAL

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

Drug: Lu AF35700

DBT Period, Continued treatment from PC Period

EXPERIMENTAL

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

Drug: Risperidone; Drug: Olanzapine

Interventions

Lu AF35700 DRUG

10 mg/day, encapsulated tablets, orally

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

Risperidone DRUG

4-6 mg/day, encapsulated tablets, orally

DBT Period, Continued treatment from PC Period; Prospective Confirmation (PC) Period

Olanzapine DRUG

15-20 mg/day, encapsulated tablets, orally

DBT Period, Continued treatment from PC Period; Prospective Confirmation (PC) Period

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lundbeck A/S: lead

Study Sites (41)

University of California San Diego Health System

San Diego, California, 92103, United States

Location

Emory University Cognitive Neurology Clinic & ADRC

Atlanta, Georgia, 30329, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Corrigan Mental Health Center

Fall River, Massachusetts, 02720, United States

Location

University Of Massachusetts Medical Center

Worcester, Massachusetts, 01605-2610, United States

Location

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, 48108, United States

Location

Kalamazoo Community Mental Health and Substance Abuse Services

Kalamazoo, Michigan, 49001, United States

Location

PsychCare Consultants Research

St Louis, Missouri, 63128, United States

Location

Creighton University

Omaha, Nebraska, 68131, United States

Location

Psychiatric and Behavioral Solutions

Salt Lake City, Utah, 84105, United States

Location

SPH - Kardzhali

Kardzhali, Bulgaria

Location

State Psychiatric Hospital

Novi Iskar, Bulgaria

Location

UMHAT

Pleven, Bulgaria

Location

State Psychiatric Hospital

Radnevo, Bulgaria

Location

DCC St. Vrach and St.St. Kuzma and Damian

Sofia, Bulgaria

Location

MHC - Sofia

Sofia, Bulgaria

Location

MHAT - Targovishte

Targovishte, Bulgaria

Location

Takeda General Hospital - JP0009

Aizu-Wakamatsu, Japan

Location

Takeda General Hospital

Fukushima, Japan

Location

Kohnodai Hospital

Ichikawa, Japan

Location

Nara Medical University Hospital

Kashihara, Japan

Location

Sankeikai Nishigahara Hospital - JP0008

Kita-ku, Japan

Location

University of Occupational and Environmental Health Hospital

Kitakyushu, Japan

Location

National Center of Neurology and Psychiatry

Kodaira, Japan

Location

Satokai Yuge Hospital

Kumamoto, Japan

Location

NHO Ryukyu Hospital

Kunigami, Japan

Location

Fujita Health University Hospital

Toyoake, Japan

Location

GUZ Lipetsk Regional psychoneurological Hospital 1

Lipetsk, Russia

Location

Lipetsk Regional Psychoneurological Hospital

Lipetsk, Russia

Location

City Psychiatric Hospital # 6

Saint Petersburg, Russia

Location

Psychoneurological Dispensary #10

Saint Petersburg, Russia

Location

Psychoneurological Dispensary #1

Saint Petersburg, Russia

Location

Samara Psychiatric Hospital

Samara, Russia

Location

Tomsk National Research Medical Centre of the Russian Academy of Sciences

Tomsk, Russia

Location

Yaroslavl Regional Clinical Psychiatric Hospital

Yaroslavl, Russia

Location

Sverdlovsk Regional Clinical Psychiatric Hospital

Yekaterinburg, Russia

Location

Royal Edinburgh Hospital

Edinburgh, United Kingdom

Location

The Maudsley Hospital - GB0001

London, United Kingdom

Location

The Maudsley Hospital

London, United Kingdom

Location

Manchester Mental Health & Social Care NHS Trust - GB0003

Manchester, United Kingdom

Location

Manchester Mental Health & Social Care NHS Trust

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant

Interventions

Lu AF35700; Risperidone; Olanzapine

Condition Hierarchy (Ancestors)

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study was terminated early and hence the statistical analysis was conducted on a smaller sample size than originally planned.

Results Point of Contact

• Title: Email contact via
• Organization: H. Lundbeck A/S

LundbeckClinicalTrials@Lundbeck.com

+4536301311

Study Officials

• Email contact via H.Lundbeck A/S

  LundbeckClinicalTrials@Lundbeck.com

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: July 27, 2017
• Study Start: July 20, 2017
• Primary Completion: December 23, 2018
• Study Completion: February 5, 2019
• Last Updated: January 21, 2020
• Results First Posted: January 7, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); JP (10); RU (9); US (10); BU (7)