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

Lundbeck

Status and phase: Terminated; Phase 3

Conditions: Treatment-resistant Schizophrenia

Treatments: Drug: Risperidone; Drug: Olanzapine; Drug: Lu AF35700

Study type: Interventional

Funder types: Industry

Identifiers

NCT03230864

17303A

Details and patient eligibility

About

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)

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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

Enrollment: 119 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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119 participants in 3 patient groups

Prospective Confirmation (PC) Period

Experimental group

Description:

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

Treatment:

Drug: Risperidone

Drug: Olanzapine

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

Experimental group

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

Treatment:

Drug: Lu AF35700

DBT Period, Continued treatment from PC Period

Experimental group

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

Treatment:

Drug: Risperidone

Drug: Olanzapine