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

NCT ID: NCT01483846

Last Updated: 2012-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2012-09-30

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.

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.

Conditions

Neuropathic Pain

Keywords

Neuropathic Pain; Capsaicin Induced Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

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Group Type: EXPERIMENTAL

AV-101

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

AV-101

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

L-4-Cl-KYN; microcrystalline cellulose

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cato Research

INDUSTRY

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

VistaGen Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph Snodgrass, PhD

Role: STUDY_DIRECTOR

VistaGen Therapeutics, Inc.

Locations

UCSD Medical Center

San Diego, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29229209 (View on PubMed)

Other Identifiers

R44DA018515

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VSG-CL-002

Identifier Type: -

Identifier Source: org_study_id