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

This study has been completed.
Sponsor:
Collaborators:
Cato Research
Information provided by (Responsible Party):
VistaGen Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01483846
First received: November 16, 2011
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Neuropathic Pain
Drug: AV-101
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by VistaGen Therapeutics, Inc.:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.

  • Safety [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Antihyperalgesic activity [ Time Frame: 28-49 Days ] [ Designated as safety issue: No ]
    To examine the antihyperalgesic effects of orally-administered, multiple doses of AV-101 in healthy volunteers by using the intradermal capsaicin model.


Enrollment: 50
Study Start Date: December 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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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 Name: 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 Name: microcrystalline cellulose

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.

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483846

Locations
United States, California
UCSD Medical Center
San Diego, California, United States, 92037
Sponsors and Collaborators
VistaGen Therapeutics, Inc.
Cato Research
Investigators
Study Director: Ralph Snodgrass, PhD VistaGen Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: VistaGen Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01483846     History of Changes
Other Study ID Numbers: VSG-CL-002, R44DA018515
Study First Received: November 16, 2011
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by VistaGen Therapeutics, Inc.:
Neuropathic Pain
Capsaicin Induced Pain

Additional relevant MeSH terms:
Neuralgia
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Diseases
Pain
Peripheral Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on November 19, 2014