Study to Assess the Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Effects of EVP-6308 and the Potential of EVP-6308 to Affect the PK Properties of the Antipsychotic Regimen in Subjects With Schizophrenia Currently Receiving Stable Treatment With up to 2 Atypical Antipsychotics

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, sequential cohort, ascending oral dose study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of EVP-6308 administered for 14 days in subjects with schizophrenia who are on a stable anti-psychotic regimen.

Official Title
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A Double-Blind, Escalating Dose Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Evaluation of Repeat Doses of EVP-6308 or Placebo in Subjects With Schizophrenia on a Stable Antipsychotic Regimen

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Drug: EVP-6308
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Diagnosed with schizophrenia, male or female subjects, 18 to 60 years of age Exclusion Criteria: Clinically significant abnormalities on physical examination, medical history, ECG, vital signs, laboratory values, or unstable medical or psychiatric illness Any disorder that may interfere with drug absorption Clinically significant allergy or sensitivity to medications Positive test for human immunodeficiency virus (HIV) antibodies, Hepatitis B surface antigen, or Hepatitis C antibody Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: EVP-6308; Arm 1<br>low dose, Capsule, Twice Daily, Day 1 through Day 14 | Drug: Drug: EVP-6308<br>* Arms 1, 2, 3<br>|
| Experimental: Experimental: EVP-6308; Arm 2<br>intermediate dose, Capsule, Once Daily, Day 1 through Day 14 | Drug: Drug: EVP-6308<br>* Arms 1, 2, 3<br>|
| Experimental: Experimental: EVP-6308; Arm 3<br>high dose, Capsule, Once Daily, Day 1 through Day 14 | Drug: Drug: EVP-6308<br>* Arms 1, 2, 3<br>|
| Placebo Comparator: Placebo Comparator; Arm 4<br>Placebo, Capsule, Once Daily, Day 1 through Day 14 | Drug: Placebo<br>* Arm 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of EVP-6308 in subjects with schizophrenia currently receiving stable treatment with up to 2 atypical antipsychotics | Vital signs measurements, Clinical laboratory tests, Physical examination, ECG findings, Columbia-Suicide Severity Rating Scale. Adverse events and concomitant medications will be collected from the time of signing the informed consent. | Baseline to Day 21 or Early Termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of EVP-6308 in subjects with schizophrenia and the potential for EVP-6308 to affect the pharmacokinetic properties of the antipsychotic regimen | PK parameters to be determined for EVP-6308 and EVP-6308 N-oxide metabolite include Cmax, Tmax,, AUC, and t1/2. PK parameters to be determined for the antipsychotic include Cmax, Tmax, AUC, and CL/F. | Day -1 through Day 16 | 
| Potential pharmacodynamics effects of EVP-6308 | Quantitative EEG, Positive and Negative Syndrome Scale, Clinician Global Impression - Severity, Barnes Akathisia Rating Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale, Cognitive Battery. | Baseline to Day 21 or Early Termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phosphodiesterase 10 inhibitor