The Use of AVL-3288 to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine

NCT03281694 | Withdrawn Phase 1 DMC

• 1 other identifier: HP-0009999
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Single-center, randomized, double-blind, placebo-controlled, proof-of-principle study to evaluate potential cognitive benefits of a single oral dose of AVL-3288 (3 mg) in the presence and absence of transdermal nicotine (7 mg/24 hrs) in healthy non-smokers, while monitoring the safety and tolerability of AVL-3288.

Conditions

Cognitive Change

Keywords

nicotine; positive allosteric modulator; attention; cognition

Outcome Measures

Primary Outcomes (6)

• Spatial Attentional Resource Allocation Task reaction time

  average reaction time of trials with a signal detection response

  5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day

• Spatial Attentional Resource Allocation Task omission errors

  percentage of trials on which no response was registered

  5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day

• Rapid Visual Information Processing Task signal detection

  signal detection index based on hit rate and false alarm rate

  5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day

• Rapid Visual Information Processing Task reaction time

  average reaction time on trials with a correct response

  5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day

• Change Detection Task accuracy

  % of correct responses

  5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day

• Change Detection reaction time

  average reaction time across trials

  5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day

Secondary Outcomes (3)

• Vital signs: blood pressure

  hourly for 8 hours on each test day

• Vital signs: heart rate

  hourly for 8 hours on each test day

• ECG

  Before and 4 hours after ingestion of oral solution on each test day

Study Arms (1)

Nicotine - AVL-3288 Interaction Study

OTHER

Over four different test days, all participants will be tested with Placebo, Nicotine, AVL-3288, and Nicotine + AVL-3288, in a counterbalanced sequence.

Drug: Placebo; Drug: Nicotine; Drug: AVL-3288; Drug: Nicotine + AVL-3288

Interventions

Placebo DRUG

placebo skin patch and placebo oral solution

Nicotine - AVL-3288 Interaction Study

Nicotine DRUG

nicotine skin patch (7 mg/24 hrs) and placebo oral solution

Nicotine - AVL-3288 Interaction Study

AVL-3288 DRUG

placebo skin patch and AVL-3288 oral solution (3 mg)

Nicotine - AVL-3288 Interaction Study

Nicotine + AVL-3288 DRUG

nicotine skin patch (7 mg/24 hrs) and AVL-3288 oral solution (3 mg)

Nicotine - AVL-3288 Interaction Study

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 21-50 years.
• Male or female willing to use qualified methods of contraception for the study duration and up to 2 months after its end. Qualified methods are: intrauterine device, condoms, oral contraceptives, surgical sterilization of the subject or the partner at least one year in advance, or postmenopausal status of the female defined as at least two years without menstruation.
• No exposure to any nicotine-containing product in the last year.
• Smoked no more that 40 cigarettes, cigars or cigarillos in lifetime.
• Normal or corrected to normal vision (at least 20/80).
• Body weight 110-220 lbs.

You may not qualify if:

• Pregnant or breast-feeding.
• DSM Axis I mood, anxiety or psychotic disorder.
• Drug or alcohol abuse or dependence currently or in the last 2 years.
• Cardiovascular or cerebrovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities (see below).
• Uncontrolled hypertension (resting systolic BP \>150 or diastolic \>95 mm Hg).
• Hypotension (resting systolic BP below 90 or diastolic below 60).
• Significant kidney or liver impairment.
• Moderate to severe asthma.
• Type I diabetes.
• Gastrointestinal illness.
• Use of any prescription or over-the-counter medication except birth control or non-steroidal antiinflammatory drugs on an as-needed basis.
• History of or current neurological illnesses, such as stroke, seizure disorders, neurodegenerative diseases, or organic brain syndrome.
• Learning disability, mental retardation, or any other condition that impedes cognition.
• Any surgeries requiring full anesthesia scheduled within 2 weeks of any of the study test sessions.
• Inability to perform the Rapid Visual Information Processing Task.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

MeSH Terms

Interventions

Nicotine; AVL3288

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The study will be double-blind. Only the statistician performing randomization and the dispensing pharmacist will know the sequence of test conditions.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director Maryland Psychiatric Research Center

Study Record Dates

• First Submitted: September 6, 2017
• First Posted: September 13, 2017
• Study Start: May 1, 2018
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share