Safety, Tolerability and Pharmacokinetics of Multiple Doses of AV-101 in Healthy Volunteers

December 18, 2012 updated by: VistaGen Therapeutics, Inc.

A Phase 1b, Single-Site, Randomized, Double-Blind,Placebo-Controlled, Dose-Escalation Study: Safety, Pharmacokinetics, and Antihyperalgesic Activity of Multiple Doses of AV-101 on Capsaicin-Induced Pain in Healthy Volunteers

This is a Phase 1b study involving multiple oral doses of AV-101 in healthy male and female subjects. The safety, pharmacokinetics, and antihyperalgesic effect of AV-101 on capsaicin-induced hyperalgesia will be assessed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Healthy subjects will be randomized into three dose cohorts (360, 1,080, and 1,440 mg) to receive daily oral doses of AV-101 for 14 consecutive days. Each cohort has 12 subjects on active drug and 4 subjects on placebo. Safety, PK, and antihyperalgesic effects of treatment with AV-101 will be assessed.

At the screening visit between Day -28 and Day -7 before randomization, 250 μg of capsaicin will be intradermally delivered into the volar aspect of one forearm. Subjects must report a pain score of at least 4 out of 10 to qualify for the study. On Day 1 and Day 14 the following data are collected: (1) neurosensory testing (thermal sensation, thermal pain, touch, and mechanical pain) on the forearm; (2) neurocognitive evaluation; and (3) 12-lead electrocardiogram, blood pressure, heart rate, respiratory rate, and temperature. PK samples will be collected on Days 1, 2, 14, and 15. The capsaicin-induced pain will be assessed at screening, on Day 1, and Day 14. An intradermal injection of capsaicin into the forearm on Day 1 and Day 14 will be followed by the efficacy measures. On Day 1 before administration of the first dose, subjects will be given a paper diary to record daily self-administration of each dose, concomitant medications, and adverse events during the 14-day treatment period.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92037
        • UCSD Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A subject will be eligible for participation in the full study only if all of the following criteria are met:

    1. Be male or female, aged 21 to 60 years inclusive, healthy, able and willing to provide written informed consent to participate in the study.
    2. Be able to read and speak English sufficiently to understand and follow the study instructions, including completion of pain intensity rating scales.
    3. For males, must use birth control (condom) to prevent fathering children; for females must be nonlactating, not pregnant, and using a reliable contraception method (e.g., abstinence, intrauterine device, hormonal birth control, or double barrier method [male condom, female condom, or diaphragm plus a spermicidal agent such as contraceptive foam, jelly, or cream]).
    4. Have a visual analog pain score of at least 4 out of 10 at screening.

Exclusion Criteria:

  • Subjects will be excluded from the study if any one or more of the following conditions apply:

    1. History of peripheral neuropathy or any chronic pain condition.
    2. History of significant hepatic, ophthalmic (including previous or current cataract), cardiovascular, renal, gastrointestinal, hematological, neurological, endocrine (including diabetes), metabolic, pulmonary, or psychiatric disease. Significance will be determined by the principal investigator.
    3. Clinically significant abnormality on the screening electrocardiogram that in the judgment of the investigator would place the subject at risk of cardiac adverse event as a result of capsaicin injection or administration of AV-101.
    4. Cognitive or psychiatric disorders that may diminish compliance with study procedures.
    5. Dermatopathology, skin hypersensitivity, or skin lesions in the areas of capsaicin application.
    6. Allergy to capsaicin or the study medication.
    7. Current tobacco use.
    8. Use of chemotherapy agents or history of cancer, other than resolved skin cancer, within 5 years before the screening visit.
    9. History of drug or alcohol abuse within 1 year before screening.
    10. History of AIDS, testing as HIV positive, or use of antiretroviral therapy.
    11. Use of, within 4 weeks before study drug dosing, any investigational drug, any epidural or intrathecal agent, corticosteroids, topical anesthetics, topical analgesics, central alpha agents (e.g., clonidine), alpha blockers (e.g., praxosin, terazosin), beta blockers, calcium channel blockers, or ACE inhibitors.
    12. Use within 7 days before and during the entire period of study drug dosing of long-acting nonsteroidal anti-inflammatory drug (NSAIDs) such as piroxicam or naproxen.
    13. Use within 36 hours before and during the entire period of study drug dosing of NSAIDs, aspirin, acetaminophen, antihistamines, sympathomimetics (e.g., pseudoephedrine and ephedrine), caffeine or alcohol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AV-101

Subjects will be randomized into one of three dose cohorts (360, 1,080, and 1,440 mg) to receive a daily oral dose for 14 consecutive days. Each cohort will have 12 subjects on active drug and 4 subjects on placebo.

--------------------------------------------------------------------------------
Drug: AV-101
Placebo or AV-101 at 360 mg, 1080 mg, or 1440 mg will be dosed once daily for 14 consecutive days.
Other Names:
  • L-4-Cl-KYN
Placebo Comparator: microcrystalline cellulose
Subjects will be randomized into one of three cohorts (360, 1,080, and 1,440 mg) to receive a daily oral dose for 14 consecutive days. Each cohort will have 12 subjects on active drug and 4 subjects on placebo.
Drug: Placebo
Placebo or AV-101 at 360 mg, 1080 mg, or 1440 mg will be dosed once daily for 14 consecutive days.
Other Names:
  • microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetics
Time Frame: PK samples will be collected at time 0, 0.5, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dosing on Day 1 and Day 14.
To evaluate pharmacokinetics of three dose levels of orally-administered AV-101 given once a day for 14 days in healthy volunteers by measuring Cmax, half-life, Tmax, and AUC.
PK samples will be collected at time 0, 0.5, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dosing on Day 1 and Day 14.
Safety
Time Frame: 28 days
To evaluate the safety of three dose levels of orally-administered AV-101 given once a day for 14 days in healthy volunteers by evaluating the number of subjects with treatment-emergent adverse events and changes from baseline to end of study in vital signs, hematology, hepatic profile, renal profile, urinalysis, and clinical laboratory parameters.
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Antihyperalgesic activity
Time Frame: 28-49 Days
To examine the antihyperalgesic effects of orally-administered, multiple doses of AV-101 in healthy volunteers by using the intradermal capsaicin model.
28-49 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VistaGen Therapeutics, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)
Cato Research

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Ralph Snodgrass, PhD, VistaGen Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 16, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 1, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 20, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VSG-CL-002
  • R44DA018515 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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