Clinical trial NCT01851603: Phase I Study to Evaluate the Safety and Pharmacokinetics of Oral Doses of Anvylic-3288 in Healthy Subjects
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Schizophrenia
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2013-05-10
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a brief inpatient study to determine the safety of a new drug in healthy people.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteer

Exclusion Criteria:

* Substance use. We do not accept inquiries by email.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 48 hours
Secondary outcomes:
measure: Number of participants with adverse events.
timeFrame: 10 days
Other outcomes:
measure: Repeatable Battery for Assessment of Neuropsychological Status Total Scale T Score
timeFrame: 24 hours
measure: P50 Auditory Sensory Gating Ratio
timeFrame: 24 hours
Locations:
city: Aurora
country: United States
facility: U of Colorado Denver
state: Colorado
Study officials:
affiliation: U of Colorado Denver
name: Robert Freedman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.