A 26-Week Extension Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy

Study Overview
=================
Brief Summary
-----------------
This study is being conducted to further investigate the safety of prolonged exposure to EVP-6124 in subjects with Schizophrenia receiving a stable dose of an atypical antipsychotic who completed double-blind treatment on studies EVP-6124-015 and EVP-6124-016.

Official Title
-----------------
A Multicenter 26-Week Extension Study to Evaluate the Safety and Clinical Effects of Prolonged Exposure to Two Doses of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, as an Adjunctive Pro-cognitive Treatment in Subjects With Schizophrenia on Chronic Stable Atypical Antipsychotic Therapy

Conditions
-----------------
Schizophrenia, Impaired Cognition

Intervention / Treatment
-----------------
* Drug: EVP-6124


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Completion of the Day 182 visit in a previous 26-week double-blind study (EVP-6124-015 or EVP-6124-016). Subject has signed informed consent for this extension study, indicating that the subject understands the purpose of and procedures required for the study, before the initiation of any extension study specific procedures. Subjects who are unable to provide informed consent will not be included in the study No clinically significant changes in the subject's medical status during the participation in EVP-6124-015 or EVP-6124-016. Any significant changes in health care status and their impact on subject eligibility will be reviewed by the investigator and sponsor on a case-by-case basis. In the opinion of the investigator, the extension treatment is in the best interest of the subject. Fertile, sexually active subjects (men and women) must use an effective method of contraception during the study. Females and the female partners of male must be surgically sterile (hysterectomy or bilateral tubal ligation), postmenopausal for at least 1 year, willing to practice adequate methods of contraception if of childbearing potential (defined as consistent use of combined effective methods of contraception [including at least one barrier method]). Female subjects must have a negative urine pregnancy test predose on Day 1. Exclusion Criteria: Significant risk for suicidal or violent behavior, as determined by the investigator. Significant risk for suicidal behavior is defined as 1) suicidal ideation as endorsed on items 4 and 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS); 2) suicidal behaviors detected by the C-SSRS; or 3) psychiatric interview and examination. Adverse events from the previous study (EVP-6124-015 or EVP-6124-016) that have not resolved, are of moderate or greater severity and judged to be possibly related or related to study drug and are thought by the investigator to be contraindications to study participation. Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study. Female subjects who are pregnant. Subjects who received any other investigational treatment during participation in either EVP-6124-015 or EVP-6124-016 other than assigned study medication.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVP-6124 low dose<br>low dose Tablet, Once Daily, Day 1 through Day 182 | Drug: EVP-6124<br>* Arm 1, 2<br>|
| Experimental: EVP-6124, high dose<br>high dose Tablet, Once Daily, Day 1 through Day 182 | Drug: EVP-6124<br>* Arm 1, 2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of EVP-6124 or Placebo in Subjects with Schizophrenia | All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG, and laboratory tests (hematology/blood/chemistry/urinalysis) | Baseline through Day 182 or Early Termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Clinical Global Impression (CGI) - Severity (CGI-S) to Day 182 |  | Baseline to Day 182 or Early Termination | 
| Change from Baseline in the Clinical Global Impression (CGI) - Change (CGI-C) to Day 182 |  | Baseline to Day 182 or Early Termination | 
| Change from Baseline in the EuroQol-5D (EQ-5D-5L) to Day 182 |  | Baseline to Day 182 or Early Termination | 
| Change from Baseline in the Columbia Suicide Severity Rating Scale (C-SSRS) to Day 182 |  | Baseline to Day 182 or Early Termination | 
| Change from Baseline in the Client Socio-Demographic and Service Receipt Inventory-European Version (CSSRI-EU) to Day 182 |  | Baseline to Day 182 or Early Termination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia, Cognition, Cognition Impairment, Alpha-7 nAChR