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

Treatment-resistant Schizophrenia Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03230864
• Other study ID #: 17303A
• Status: Terminated
• Phase: Phase 3
• Start date: July 20, 2017
• Est. completion date: February 5, 2019

Study information

• Verified date: January 2020
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 119
• Est. completion date: February 5, 2019
• Est. primary completion date: December 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia
• Treatment-resistant Schizophrenia

Intervention

Drug:
• Lu AF35700
10 mg/day, encapsulated tablets, orally
• Risperidone
4-6 mg/day, encapsulated tablets, orally
• Olanzapine
15-20 mg/day, encapsulated tablets, orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  Japan,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Response	Response is defined as a =20% reduction in PANSS total score from Randomization	at Week 8