Phase I Study to Evaluate the Safety and Pharmacokinetics of Oral Doses of Anvylic-3288 in Healthy Subjects

Study Overview
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Brief Summary
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This is a brief inpatient study to determine the safety of a new drug in healthy people.

Detailed Description
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AVL-3288, a first in class small molecule, selective allosteric modulator of the α7 nAChR, is implicated in the cognitive deficit in patients with neurologic and psychiatric disorders, including schizophrenia, Alzheimer's disease and attention deficit hyperactivity disorder. The mechanism of action, the allosteric modulation of α7 nAChR and improvement of cognitive and memory function both in relevant animal models and patients has been clearly described in recent literature. The effect of AVL-3288 strongly supports the rationale for use in schizophrenia given the dose effect relationship, peaking at a low dose in rats (HED 3 mg), in rodent schizophrenia and memory models. Phase I, single-center, inpatient, randomized, double-blind, placebo-controlled, dose escalating study to evaluate the safety, tolerability and pharmacokinetic profiles of single oral doses of AVL-3288 in healthy subjects. Subjects will be hospitalized in the University of Colorado Clinical Research Center (CTSA) for a 12 hour period after the single dose. Then there will be an ambulatory 24 and 48 hour observation and washout period of 10. Patients will receive an evoked potential measurement, the P50 sensory gating paradigm, and the Repeatable Battery for Assessment of Neuropsychological Status.

Official Title
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Phase I, Single-center, Inpatient, Randomized, Double-blind, Placebo-controlled, Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profiles of Single Oral Doses of AVL-3288 (Anvylic-3288) Healthy Subjects.

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: AVL-3288
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteer Exclusion Criteria: Substance use. We do not accept inquiries by email.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVL-3288<br>Oral administration of AVL-3288 | Device: AVL-3288<br>* Drug<br>* Other names: UCI-4083;|
| Placebo Comparator: Sugar pill<br>Placebo | Drug: Placebo<br>* Identical diluent to that used for AVL-3288<br>* Other names: Diluent solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | 0,1,2,3, 4, 6, 8 ,12, 24, 48 hours post dose | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events. | Corrected QT interval > 500 ms; hepatic enzyme > 3 times above the upper limit of normal values; systolic blood pressure > 200 mm Hg or diastolic blood pressure < 50 mm Hg. | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia