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

Schizophrenia Clinical Trial

— AVL3288  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01851603
• Other study ID #: 12-1186
• Secondary ID: 1U01MH094247
• Status: Terminated
• Phase: Phase 1
• First received: May 6, 2013
• Last updated: December 28, 2016
• Start date: June 2013
• Est. completion date: August 2016

Study information

• Verified date: December 2016
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Healthy volunteer

Exclusion Criteria:

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Device:
• AVL-3288
Drug

Drug:
• Placebo
Identical diluent to that used for AVL-3288

Locations

Country	Name	City	State
United States	U of Colorado Denver	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Primary	Maximum Observed Plasma Concentration (Cmax)	0,1,2,3, 4, 6, 8 ,12, 24, 48 hours post dose	48 hours	No
Secondary	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	Yes