Safety and Tolerability of GATE-251 in Normal Human Volunteers

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of single ascending doses of GATE-251 in normal human volunteers

Detailed Description
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Single ascending dose (SAD), double-blind placebo-controlled study in normal human volunteers. Secondary objectives: To evaluate the pharmacokinetics (PK) and eeg biomarker of target engagement of GATE-251 following increasing single doses of GATE-251. GATE-251 or Placebo: Dose/Mode of Administration: Single dose; oral

Official Title
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A Phase 1, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AGN-241751 After Oral Administration in Healthy Volunteers

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: GATE-251
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agree to effective method of birth control If female, negative pregnancy test at screening and Day -1 Nonsmoking at least 2 years BMI 18-30 Supine pulse rate 30-100 Exclusion Criteria: Known hypersensitivity to NMDA receptor drugs clinically significant disease in any body system QTcF > 430 ms in males, >450 ms in females positive test for hepatitis B or C abnormal liver function tests on Day -1 History of alcohol or other substance abuse during the previous 5 years Positive drug screen at screening or Day -1 Taken any medication within the past 14 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind placebo controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 microgram GATE-251<br>GATE-251, 100 microgram tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 1 mg GATE-251<br>GATE-251, 1 mg tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 3 mg GATE-251<br>GATE-251, 3 mg tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 10 mg GATE-251<br>GATE-251, 10 mg tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 25 mg GATE-251<br>GATE-251, 25 mg tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 50 mg GATE-251<br>GATE-251, 50 mg tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 100 mg GATE-251<br>GATE-251, 100 mg tablet, PO, Single Dose with 28 day follow up | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 1 mg GATE-251 with CSF collection<br>GATE-251, 1 mg tablet, PO, Single Dose with 28 day follow up, with CSF collection | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Experimental: 10 mg GATE-251 with CSF collection<br>GATE-251, 10 mg tablet, PO, Single Dose with 28 day follow up, with CSF collection | Drug: GATE-251<br>* Single dose of GATE-251<br>|
| Placebo Comparator: Placebo<br>Placebo tablet, PO, Single Dose with 28 day follow up | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events | through study completion | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics, maximum plasma concentration | maximum plasma concentration | 24 hours | 
| Pharmacokinetics, time to maximum plasma concentration | time to maximum plasma concentration | 24 hours | 
| Pharmacokinetics, area under the curve for plasma concentration | area under the curve, plasma calculated 0-infinity | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NMDA receptor, NMDA receptor positive allosteric modulator, pharmacokinetics, biomarker, eeg