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

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

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)

Study Overview

• Status: Terminated
• Conditions: Treatment-resistant Schizophrenia
• Intervention / Treatment: Drug: Risperidone; Drug: Olanzapine; Drug: Lu AF35700

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Kardzhali, Bulgaria
    • SPH - Kardzhali
  • Novi Iskar, Bulgaria
    • State Psychiatric Hospital
  • Pleven, Bulgaria
    • UMHAT
  • Radnevo, Bulgaria
    • State Psychiatric Hospital
  • Sofia, Bulgaria
    • DCC St. Vrach and St.St. Kuzma and Damian
  • Sofia, Bulgaria
    • MHC - Sofia
  • Tărgovište, Bulgaria
    • MHAT - Targovishte
• Japan
  • Aizu-Wakamatsu, Japan
    • Takeda General Hospital - JP0009
  • Fukushima, Japan
    • Takeda General Hospital
  • Ichikawa, Japan
    • Kohnodai Hospital
  • Kashihara, Japan
    • Nara Medical University Hospital
  • Kita, Japan
    • Sankeikai Nishigahara Hospital - JP0008
  • Kitakyushu, Japan
    • University Of Occupational And Environmental Health Hospital
  • Kodaira, Japan
    • National Center of Neurology and Psychiatry
  • Kumamoto, Japan
    • Satokai Yuge Hospital
  • Kunigami, Japan
    • NHO Ryukyu Hospital
  • Toyoake, Japan
    • Fujita Health University Hospital
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Sverdlovsk Regional Clinical Psychiatric Hospital
  • Lipetsk, Russian Federation
    • Lipetsk regional psychoneurological hospital
  • Lipetsk, Russian Federation
    • GUZ Lipetsk Regional psychoneurological Hospital 1
  • Saint Petersburg, Russian Federation
    • City Psychiatric Hospital # 6
  • Saint Petersburg, Russian Federation
    • Psychoneurological Dispensary #10
  • Saint Petersburg, Russian Federation
    • Psychoneurological Dispensary #1
  • Samara, Russian Federation
    • Samara Psychiatric Hospital
  • Tomsk, Russian Federation
    • Tomsk National Research Medical Centre of the Russian Academy of Sciences
  • Yaroslavl, Russian Federation
    • Yaroslavl Regional Clinical Psychiatric Hospital
• United Kingdom
  • Edinburgh, United Kingdom
    • Royal Edinburgh Hospital
  • London, United Kingdom
    • The Maudsley Hospital - GB0001
  • London, United Kingdom
    • The Maudsley Hospital
  • Manchester, United Kingdom
    • Manchester Mental Health & Social Care NHS Trust - GB0003
  • Manchester, United Kingdom
    • Manchester Mental Health & Social Care NHS Trust
• United States
  • California
    • San Diego, California, United States, 92103
      • University of California San Diego Health System
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University Cognitive Neurology Clinic & ADRC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Corrigan Mental Health Center
    • Worcester, Massachusetts, United States, 01605-2610
      • University of Massachusetts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48108
      • Michigan Clinical Research Institute PC
    • Kalamazoo, Michigan, United States, 49001
      • Kalamazoo Community Mental Health and Substance Abuse Services
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric and Behavioral Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prospective Confirmation (PC) Period; Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks	Drug: Risperidone; 4-6 mg/day, encapsulated tablets, orally; Drug: Olanzapine; 15-20 mg/day, encapsulated tablets, orally
Experimental: Double-blind treatment (DBT) period, Lu AF35700 10 mg; 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; 10 mg/day, encapsulated tablets, orally
Experimental: DBT Period, Continued treatment from PC Period; 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; 4-6 mg/day, encapsulated tablets, orally; Drug: Olanzapine; 15-20 mg/day, encapsulated tablets, orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From Randomization to Week 8
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.	From Randomization to Week 8
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.	From Randomization to Week 8
Response	Response is defined as a ≥20% reduction in PANSS total score from Randomization	at Week 8

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2017
• Primary Completion (Actual): December 23, 2018
• Study Completion (Actual): February 5, 2019

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Treatment-resistant schizophrenia; Lu AF35700
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Olanzapine; Risperidone
• Other Study ID Numbers: 17303A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No