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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03230864
Recruitment Status : Terminated (New data; the study was terminated based on new efficacy data from another study)
First Posted : July 27, 2017
Results First Posted : January 7, 2020
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S

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)

Condition or disease Intervention/treatment Phase
Treatment-resistant Schizophrenia Drug: Lu AF35700 Drug: Risperidone Drug: Olanzapine Phase 3

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 20, 2017
Actual Primary Completion Date : December 23, 2018
Actual Study Completion Date : February 5, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

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




Primary Outcome Measures :
  1. Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: From Randomization to Week 8 ]
    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 :
  1. Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score [ Time Frame: From Randomization to Week 8 ]
    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

  2. Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score [ Time Frame: From Randomization to Week 8 ]
    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.

  3. Change From Randomization to Week 8 in PANSS Marder Negative Factor Score [ Time Frame: From Randomization to Week 8 ]
    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.

  4. Response [ Time Frame: at Week 8 ]
    Response is defined as a ≥20% reduction in PANSS total score from Randomization



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03230864


Locations
Show Show 41 study locations
Sponsors and Collaborators
H. Lundbeck A/S
Investigators
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Study Director: Email contact via H.Lundbeck A/S LundbeckClinicalTrials@Lundbeck.com
  Study Documents (Full-Text)

Documents provided by H. Lundbeck A/S:
Study Protocol  [PDF] September 7, 2018
Statistical Analysis Plan  [PDF] March 13, 2019

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Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT03230864    
Other Study ID Numbers: 17303A
First Posted: July 27, 2017    Key Record Dates
Results First Posted: January 7, 2020
Last Update Posted: January 21, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lundbeck A/S:
Treatment-resistant schizophrenia
Lu AF35700
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Olanzapine
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators