A Study to Evaluate the Effects of Basmisanil in Participants With Cognitive Impairment Associated With Schizophrenia (CIAS) Treated With Antipsychotics

Schizophrenia Clinical Trial

Official title:

A Phase IIb, Multicenter, Randomized, Double-Blind, Parallel Group, Placebo Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Basmisanil (RO5186582) as Adjunctive Treatment in Patients With Cognitive Impairment Associated With Schizophrenia Treated With Antipsychotics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02953639
• Other study ID #: BP39207
• Status: Completed
• Phase: Phase 2
• Start date: November 30, 2016
• Est. completion date: December 12, 2019

Study information

• Verified date: January 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter study assessed the effects of 24 weeks of basmisanil treatment on cognition and functioning of stable schizophrenia participants treated with antipsychotics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: December 12, 2019
• Est. primary completion date: December 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Diagnosis of schizophrenia of any type utilizing the Mini International Neuropsychiatric Interview and diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) direct clinical assessments, family informants and past medical records
• Evidence of stability of symptoms for 3 months at screening, that is, without hospitalizations for schizophrenia or increase in level of psychiatric care due to worsening of symptoms of schizophrenia
• Participants with schizophrenia clinical symptom severity defined by the following:

hallucinatory behavior item score less than or equal to (</=) 5 and a delusion item score </= 5 of the PANSS

• Participants on a stable regimen of antipsychotic therapy for at least 3 months at screening and receiving no more than two antipsychotics

Exclusion Criteria:

• Participants with current DSM-5 diagnosis other than schizophrenia including bipolar disorder, schizoaffective disorder and major depressive disorder
• Clinically significant neurological illness or significant head trauma that affects cognitive function, in the judgment of the principal investigator
• Full scale intelligence quotient </=65 on the Wechsler Abbreviated Scale of Intelligence at screening
• Positive result at screening for hepatitis B, hepatitis C, or human immunodeficiency virus-1 and 2
• Moderate to severe substance use disorder (other than nicotine or caffeine), as defined by the DSM-5, within the last 12 months
• Suicide attempt within 1 year or currently at risk of suicide in the opinion of the Investigator

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Schizophrenia

Intervention

Drug:
• Basmisanil
Participants received either 80 milligrams (mg) or 240 mg of Basmisanil, as per the dosing schedules described above.
• Placebo
Participants received matching Placebo to Basmisanil, as per the dosing schedules described above.

Locations

Country	Name	City	State
United States	Community Clinical Research Center	Anderson	Indiana
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Hassman Research Institute	Berlin	New Jersey
United States	Boston Medical Center	Boston	Massachusetts
United States	Neuro-Behavioral Clinical Research, Inc.	Canton	Ohio
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	University Hospitals	Cleveland	Ohio
United States	ProScience Research Group	Culver City	California
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	iResearch Atlanta	Decatur	Georgia
United States	CBH Health	Gaithersburg	Maryland
United States	Collaborative Neuroscience Network, Inc.	Garden Grove	California
United States	Pillar Clinical Research LLC	Garland	Texas
United States	California Clinical Trials	Glendale	California
United States	Alexian Brothers Center for Psychiatric Research	Hoffman Estates	Illinois
United States	University Hills Clinical Research - Irving;Office of Dr. Knesevich	Irving	Texas
United States	Vantage Clinical Trials	Largo	Florida
United States	Innovative Clinical Research, Inc.	Lauderhill	Florida
United States	Woodland International Research Group Inc.	Little Rock	Arkansas
United States	Alliance for Wellness, dba Alliance for Research	Long Beach	California
United States	Meridien Research	Maitland	Florida
United States	University of Miami Dept of Psychiatry	Miami	Florida
United States	Synergy Clinical Research	National City	California
United States	Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic	New Haven	Connecticut
United States	Manhattan Psychiatric Center; Psychopharmacology Research Unit	New York	New York
United States	Behavioral Clinical Research, Inc.	North Miami	Florida
United States	Pacific Research Partners, LLC	Oakland	California
United States	NRC Research Institute	Orange	California
United States	CNRI - Los Angeles, LLC	Pico Rivera	California
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Woodland Research Northwest, LLC	Rogers	Arkansas
United States	Arch Clinical Trials, LLC	Saint Louis	Missouri
United States	St Louis Clinical Trials	Saint Louis	Missouri
United States	Artemis Institute for Clinical Research, LLC	San Diego	California
United States	Booker, J. Gary, MD, APMC	Shreveport	Louisiana
United States	Louisiana Clinical Research, LLC	Shreveport	Louisiana
United States	Collaborative Neuroscience Network Inc.	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score	The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB neurocognitive composite T-score is a standardized mean of the six domain scores (excluding social cognition). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher composite T-score represents lower impairment.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in MCCB Cognitive Domain Scores	The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher T-score represents lower impairment.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score	The Paired Associates Learning (PAL I and II) of the WMS-IV (Wechsler Memory Scale Fourth edition) is a test of verbal learning and memory that requires the participant to learn novel word pairs. The participant learns the word pairs across learning trials and is asked to recall them immediately (PAL I) or after a 30-minute delay (PAL II). Data is presented here for 3 Scores: VPA I total raw score, VPA II total raw score and VPA II Recognition total raw score. The total raw score ranges for these 3 Scores are 0 to 56, 0 to 14 and 0 to 40 respectively, with larger total raw scores indicating better performance.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score	Logical memory (LM) assesses narrative memory under free-recall conditions. Two short stories are presented orally. The examinee is asked to retell each story from memory immediately after hearing it (LM I). In the delayed condition (LM II), the examinee is asked to retell both stories from the immediate condition (delayed free recall). Data is presented here for 2 Scores: LM I total raw score and LM II total raw score. The total raw score range is from 0 to 50 with larger total raw scores indicating better performance.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores	The TMT consists of two parts: Trail Making Part A, which is a part of the standard MCCB and Trail Making Part B additionally included in this study. Circles containing numbers (Part A) or both numbers and letters (Part B) must be sequentially connected. The difference (ratio) in performance between Part A and Part B reflects executive processes and will be used to assess executive functioning including cognitive set shifting abilities and data for this ratio is presented here. Smaller ratio values, hence decreases from baseline (TMT-B/TMT-A ratio values below 1) indicate higher executive functioning capabilities.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score	The PSP Total Score is an integer result in the range of 0 to 100. Larger values, hence increases from baseline in the PSP total score, indicate higher social and personal functioning.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score	The main parameter of interest for the Schizophrenia Cognition Rating Scale (SCoRS) is the SCoRS 'Total Score'. The total score range is from 0 to 80 with lower scores indicating better day-to-day functioning.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating	Values for the CGI-S Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating	Values for the CGI-I Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment.	Baseline up to Week 24
Secondary	Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS)	The SQLS is a patient reported scale consisting of 33 items: 2 domain scores (Cognition & Vitality Score [SQLS-CV] and Psycho-social Score [SQLS-P]) as well as a Total score (SQLS-T) are derived. The overall score range is from 0 to 100. On all scales, higher scores represent a lower quality of life.	Baseline up to Week 24
Secondary	Percentage of Participants With Adverse Events (AEs)	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.	Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
Secondary	Apparent Clearance of Basmisanil at Steady State (CL/F,ss)	Population PK model estimated apparent oral clearance of Basmisanil at steady-state.	Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Secondary	Apparent Volume of Distribution of Basmisanil at Steady State (Vz/F,ss)	Population PK model estimated apparent volume of distribution of Basmisanil at steady-state.	Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Secondary	Area Under the Curve of Basmisanil at Steady State (AUC,ss)	Population PK model estimated AUC of Basmisanil at steady-state.	Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Secondary	Maximum Plasma Concentration of Basmisanil at Steady State (Cmax,ss)	Population PK model estimated maximum plasma concentration of Basmisanil at steady-state (ss).	Pre-dose (hour 0) in Days 7, 14, 42, 84, 168