Clinical Trial of AVL-3288 in Schizophrenia Patients

Double Blind, Two Dose, Cross-over Clinical Trial of the Positive Allosteric Modulator at the alpha7 Nicotinic Cholinergic Receptor AVL-3288 in Schizophrenia Patients

Single-center, outpatient, randomized, double-blind, placebo-controlled, 3-treatment-phase, cross-over study to evaluate the safety, tolerability and efficacy of two oral doses of AVL-3288 each compared to placebo, in patients with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Drug: AVL-3288; Drug: Placebo

Detailed Description

This study will be in 24 non-smoking outpatients with schizophrenia or schizoaffective disorder. Subjects will complete three treatment phases, each involving 5 straight days of taking AVL-3288 (10 mg or 30 mg study drug or placebo) followed by a 16 day washout period in which subjects do not take the study drug to ensure that the drug is completed eliminated from the body before the next phase.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSM-V diagnosis of schizophrenia or schizoaffective disorder
• RBANS Total Scale Score >62
• Willing to provide informed consent
• Medically stable for study participation
• Taking an antipsychotic medication other than clozapine at a stable dose for at least 4 weeks
• Judged clinically not to be at significant suicide or violence risk

Exclusion Criteria:

• Substance abuse (excluding nicotine) within last 90 days
• ECG abnormality that is clinically significant
• Current clozapine use
• Participation in a study of investigational medication/device within 4 weeks
• Pregnancy, lactation, or lack of use of effective birth control
• Active tobacco use
• Presence or positive history of significant medical or neurological illness, including cardiac illness, WBC <3500/mm3, absolute neutrophil count <1500/mm3, ALT or AST values >1.5 times upper limit of normal. Hemoglobin less than 130 g/L (13 g/dL) in males or 120 g/L (12 g/dL) in females or known HIV +
• Contraindication to MRI scanning, including metal implants or claustrophobia
• Medicinal patch, unless removed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVL-3288 10 mg; AVL-3288 10 mg daily for 5 days	Drug: AVL-3288; daily for 5 days; Other Names: Anvylic-3288
Experimental: AVL-3288 30 mg; AVL-3288 30 mg daily for 5 days	Drug: AVL-3288; daily for 5 days; Other Names: Anvylic-3288
Placebo Comparator: Placebo; Placebo daily for 5 days	Drug: Placebo; daily for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score	Compare effect of active drug (AVL-3288) to placebo on RBANS total score	End of each 5-day treatment phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBANS index T-score subscales	Compare effect of active drug (AVL-3288) to placebo on RBANS index T-score subscales	End of each 5-day treatment phase
Brief Psychiatric Rating Scale (BPRS) Total score	Compare effect of active drug (AVL-3288) to placebo on BPRS Total Score.	End of each 5-day treatment phase
Calgary Depression Rating Scale (CDRS) Total score	Compare effect of active drug (AVL-3288) to placebo on CDRS Total Score.	End of each 5-day treatment phase
Scale for the Assessment of Negative Symptoms (SANS) Total score	Compare effect of active drug (AVL-3288) to placebo on SANS Total score	End of each 5-day treatment phase
P50 suppression measured by electroencephalographic (EEG)	Compare P50 suppression measured by EEG between active drug (AVL-3288) and placebo	End of each 5-day treatment phase
Intensity of hippocampal BOLD fMRI signal during MRI scan	Compare intensity of Hippocampal BOLD signal between active drug (AVL-3288) and placebo	end of each 5-day treatment phase

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Jeffrey A Lieberman, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): October 26, 2018
• Study Completion (Actual): November 2, 2018

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: 7370; U01MH094247-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes