Study of EVP-6308 to Assess the Dose- and Concentration-dependent Displacement of [18F]MNI-659 by EVP-6308

Study Overview
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Brief Summary
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This is an open-label, single-arm, multiple ascending dose Phase I study to assess the dose- and concentration-dependent displacement of [18F]MNI-659 [a PET tracer targeting phosphodiesterase 10 (PDE10)] by EVP-6308.

Official Title
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A Phase 1, Open-Label, Multiple Ascending Dose, [18F]MNI-659 PET-Imaging Study to Evaluate PDE10A Occupancy After Dosing With EVP-6308 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: EVP-6308


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Healthy male or female volunteers, 18 to 50 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. History of exposure to any radiation >15 mSv/year (e.g., occupational or radiation therapy) over the past year.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target occupancy of [18F]MNI-659. | Change in binding potential. | Baseline and Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of EVP-6308 as assessed by adverse events, vital signs, clinical laboratory tests, C-SSRS, and electrocardiogram (ECG). | The following will be evaluated: clinical laboratory evaluations (chemistry, hematology, coagulation and urinalysis), physical examination, directed neurological examination, vital signs, orthostatic blood pressure, 12-lead ECG, and assessment for suicidality. Adverse events and concomitant medications will be collected from the time of signing the informed consent. | Baseline to Day 4 or Early Termination | 
| Pharmacokinetics of EVP-6308 and EVP-6308 N-oxide. | Pharmacokinetic parameters to be determined include Cmax, Tmax, t1/2, and CL/F. | Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enzyme occupancy, Positron emission tomography (PET), Phosphodiesterase 10 inhibitor