Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1U01MH094247 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
PI left institution
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a brief inpatient study to determine the safety of a new drug in healthy people.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AVL-3288 | Experimental | Oral administration of AVL-3288 |
|
| Sugar pill | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AVL-3288 | Device | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 0,1,2,3, 4, 6, 8 ,12, 24, 48 hours post dose | 48 hours |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Repeatable Battery for Assessment of Neuropsychological Status Total Scale T Score | T score on Total Scale of the Repeatable Battery for Assessment of Neuropsychological Status, differences between AVL-3288 or placebo arms and pretreatment baseline. | 24 hours |
| P50 Auditory Sensory Gating Ratio |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Robert Freedman, MD | U of Colorado Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| U of Colorado Denver | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17470817 | Background | Ng HJ, Whittemore ER, Tran MB, Hogenkamp DJ, Broide RS, Johnstone TB, Zheng L, Stevens KE, Gee KW. Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci U S A. 2007 May 8;104(19):8059-64. doi: 10.1073/pnas.0701321104. Epub 2007 Apr 30. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo |
| Drug |
Identical diluent to that used for AVL-3288 |
|
|
Ratio = (Conditioning P50 amplitude-Test P50 Amplitude)/Conditioning P50 Amplitude, differences between AVL-3288 or placebo arms from baseline. |
| 24 hours |