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

NCT01483846 | Completed Phase 1

• 2 other identifiers: VSG-CL-002R44DA018515
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuropathic Pain

Keywords

Neuropathic Pain; Capsaicin Induced Pain

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics

  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

  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 Outcomes (1)

• Antihyperalgesic activity

  28-49 Days

Study Arms (2)

AV-101

EXPERIMENTAL

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

microcrystalline cellulose

PLACEBO COMPARATOR

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

Interventions

AV-101 DRUG

Placebo or AV-101 at 360 mg, 1080 mg, or 1440 mg will be dosed once daily for 14 consecutive days.

Also known as: L-4-Cl-KYN

AV-101

Placebo DRUG

Placebo or AV-101 at 360 mg, 1080 mg, or 1440 mg will be dosed once daily for 14 consecutive days.

Also known as: microcrystalline cellulose

microcrystalline cellulose

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A subject will be eligible for participation in the full study only if all of the following criteria are met:
• Be male or female, aged 21 to 60 years inclusive, healthy, able and willing to provide written informed consent to participate in the study.
• Be able to read and speak English sufficiently to understand and follow the study instructions, including completion of pain intensity rating scales.
• 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 \[male condom, female condom, or diaphragm plus a spermicidal agent such as contraceptive foam, jelly, or cream\]).
• Have a visual analog pain score of at least 4 out of 10 at screening.

You may not qualify if:

• Subjects will be excluded from the study if any one or more of the following conditions apply:
• History of peripheral neuropathy or any chronic pain condition.
• 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.
• 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.
• Cognitive or psychiatric disorders that may diminish compliance with study procedures.
• Dermatopathology, skin hypersensitivity, or skin lesions in the areas of capsaicin application.
• Allergy to capsaicin or the study medication.
• Current tobacco use.
• Use of chemotherapy agents or history of cancer, other than resolved skin cancer, within 5 years before the screening visit.
• History of drug or alcohol abuse within 1 year before screening.
• History of AIDS, testing as HIV positive, or use of antiretroviral therapy.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• VistaGen Therapeutics, Inc.: lead
• Cato Research: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UCSD Medical Center

San Diego, California, 92037, United States

Location

Related Publications (1)

• Wallace M, White A, Grako KA, Lane R, Cato AJ, Snodgrass HR. Randomized, double-blind, placebo-controlled, dose-escalation study: Investigation of the safety, pharmacokinetics, and antihyperalgesic activity of l-4-chlorokynurenine in healthy volunteers. Scand J Pain. 2017 Oct;17:243-251. doi: 10.1016/j.sjpain.2017.05.004. Epub 2017 Jun 15.

  PMID: 29229209 DERIVED

MeSH Terms

Conditions

Neuralgia

Interventions

microcrystalline cellulose

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ralph Snodgrass, PhD

  VistaGen Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: December 1, 2011
• Study Start: December 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 20, 2012

Record last verified: 2012-12

Locations

US (1)