Phase I Study to Evaluate the Safety and Pharmacokinetics of Oral Doses of Anvylic-3288 in Healthy Subjects (AVL3288)

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.

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

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Device: AVL-3288; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • U of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy volunteer

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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	Ratio = (Conditioning P50 amplitude-Test P50 Amplitude)/Conditioning P50 Amplitude, differences between AVL-3288 or placebo arms from baseline.	24 hours

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Robert Freedman, MD, U of Colorado Denver

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 6, 2013
• First Submitted That Met QC Criteria: May 9, 2013
• First Posted (Estimate): May 10, 2013

Study Record Updates

• Last Update Posted (Estimate): December 30, 2016
• Last Update Submitted That Met QC Criteria: December 28, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 12-1186; 1U01MH094247 (U.S. NIH Grant/Contract)