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

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

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Basmisanil

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group Inc.
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest, LLC
  • California
    • Culver City, California, United States, 90230
      • ProScience Research Group
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Glendale, California, United States, 91206
      • California Clinical Trials
    • Long Beach, California, United States, 90807
      • Alliance for Wellness, dba Alliance for Research
    • National City, California, United States, 91950
      • Synergy Clinical Research
    • Oakland, California, United States, 94607
      • Pacific Research Partners, LLC
    • Orange, California, United States, 92868
      • NRC Research Institute
    • Pico Rivera, California, United States, 90660
      • CNRI - Los Angeles, LLC
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research, LLC
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Network Inc.
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic
  • Florida
    • Largo, Florida, United States, 33770
      • Vantage Clinical Trials
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, Inc.
    • Maitland, Florida, United States, 32751
      • Meridien Research
    • Miami, Florida, United States, 33136
      • University of Miami Dept of Psychiatry
    • North Miami, Florida, United States, 33161
      • Behavioral Clinical Research, Inc.
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Center for Psychiatric Research
  • Indiana
    • Anderson, Indiana, United States, 46060
      • Community Clinical Research Center
  • Louisiana
    • Shreveport, Louisiana, United States, 71104-2136
      • Booker, J. Gary, MD, APMC
    • Shreveport, Louisiana, United States, 71115
      • Louisiana Clinical Research, LLC
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Boston Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63118
      • Arch Clinical Trials, LLC
    • Saint Louis, Missouri, United States, 63141
      • St Louis Clinical Trials
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
    • New York, New York, United States, 10035
      • Manhattan Psychiatric Center; Psychopharmacology Research Unit
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clinical Research, Inc.
    • Cleveland, Ohio, United States, 44106
      • University Hospitals
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Texas
    • Garland, Texas, United States, 75042
      • Pillar Clinical Research LLC
    • Irving, Texas, United States, 75062
      • University Hills Clinical Research - Irving;Office of Dr. Knesevich
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Placebo Comparator: Placebo; Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.	Drug: Placebo; Participants received matching Placebo to Basmisanil, as per the dosing schedules described above.
Experimental: Basmisanil 80mg BID; Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks.	Drug: Basmisanil; Participants received either 80 milligrams (mg) or 240 mg of Basmisanil, as per the dosing schedules described above.
Experimental: Basmisanil 240mg BID; Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.	Drug: Basmisanil; Participants received either 80 milligrams (mg) or 240 mg of Basmisanil, as per the dosing schedules described above.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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)
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
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
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2016
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: November 1, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: BP39207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No