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AV-101 (L-4-chlorokynurenine) in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesia

Primary Purpose

Parkinson Disease, Dyskinesia, Medication-Induced, L-Dopa Causing Adverse Effects in Therapeutic Use

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
AV-101
Placebo
Sponsored by
VistaGen Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female adults, 30 to 80 years of age, inclusive.
  2. Diagnosis of idiopathic PD meeting the United Kingdom Parkinson's disease Society Brain Bank criteria.
  3. Levodopa-induced dyskinesia present greater than 25% of the day as per MDS-UPDRS.
  4. Dyskinesia of at least moderate severity as per MDS-UPDRS
  5. Subjects currently receiving anti-parkinsonian medications that contain levodopa and carbidopa are eligible provided they have been on a stable dose of these medications for at least 1 month prior to randomization.
  6. Subjects currently receiving antidepressants such as selective serotonin reuptake inhibitors, provided the dose has been stable for at least 1 month prior to randomization.
  7. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:

    1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is postmenopausal with her last menses at least 1 year prior to screening); or
    2. . Childbearing potential, and meets all of the following criteria: i. Women with a negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment.

ii. Women who are willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, intrauterine device, sexual abstinence. The form of birth control will be documented at screening.

iii. Male partner must use a condom.

Exclusion Criteria:

  1. Women with childbearing potential who are not willing to use one of the specified forms of birth control during the study or whose partner is unwilling to use a condom.
  2. Women who are pregnant or breastfeeding.
  3. Women with a positive pregnancy test at screening or baseline.
  4. Currently taking a prohibited adjunct therapy such amantadine or monoamine oxidase (MAO) inhibitors must be discontinued at least 3 weeks prior to baseline.
  5. Subject had a prior surgery for PD except Deep Brain Stimulation (Deep Brain Stimulation must not have been performed within one year of screening)
  6. Hoehn and Yahr score of 5 when "off".
  7. Subject with Cognitive impairment and/or history of psychiatric manifestations or active hallucinations.
  8. History of positive screening urine test for drugs of abuse at screening: cannabinoids (if the subject has a legitimate medical prescription for cannabis, subject must agree to abstain during the entirety of the study and to have a negative test at baseline), cocaine, barbiturates, opiates. A positive benzodiazepine result will be allowed if there is a valid and prescribed medical use for these agents. For all other positive results, a single re-test is permitted at the judgement of the investigator; results of any retest must be available prior to the baseline visit and must be negative.
  9. In poor general health, as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and 12-lead electrocardiogram (ECG).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    AV-101

    Placebo

    Arm Description

    1440 mg of L-4-chlorokynurenine administered twice a day orally

    Matching capsules of placebo

    Outcomes

    Primary Outcome Measures

    Unified Dyskinesia Rating Scale
    (UDysRS) Part 3 AUC
    Unified Dyskinesia Rating Scale
    (UDysRS) Part 3 Peak Score

    Secondary Outcome Measures

    Movement Disorder Society- Unified Parkinson's Disease Rating Scale
    (MDS-UPDRS) part III (Parkinsonian disability)

    Full Information

    First Posted
    October 27, 2019
    Last Updated
    May 25, 2021
    Sponsor
    VistaGen Therapeutics, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04147949
    Brief Title
    AV-101 (L-4-chlorokynurenine) in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesia
    Official Title
    Randomized, Double-Blind, Placebo-Controlled, Crossover, Proof-of-Concept Phase 2 Study to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2022 (Anticipated)
    Primary Completion Date
    December 2023 (Anticipated)
    Study Completion Date
    April 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    VistaGen Therapeutics, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a randomized, double-blind, placebo-controlled, crossover, proof-of-concept Phase 2 study to test efficacy and safety of AV-101 (L-4-chlorokynurenine) in Parkinson's Disease subjects with levodopa-induced dyskinesia. The trial will be conducted in two treatment periods, in which each treatment period will consist of 14 days. The two treatment periods will be separated by a 1-week washout period. During the first treatment period, subjects meeting all eligibility criteria will be randomly assigned to receive either 1440 mg AV-101 or placebo in a 1:1 ratio. AV-101 or placebo will be administered BID for 14 days (every 12 hours). After the washout period, all subjects will be crossed over to receive the alternate treatment during the second treatment period (14-day period). On the last day of each treatment period (Visit 4 [Day 14] and Visit 7 [Day35]), subjects will be assessed in clinic while in the practically "off" state and will receive the morning dose of the study drug at the clinic. This will be followed, within 25-30 minutes, by oral administration of a dose of levodopa that is 150% of the subject's normal dose. Assessments of dyskinesia and PD motor symptoms will be performed before and after levodopa/carbidopa administration.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Parkinson Disease, Dyskinesia, Medication-Induced, L-Dopa Causing Adverse Effects in Therapeutic Use

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    AV-101
    Arm Type
    Experimental
    Arm Description
    1440 mg of L-4-chlorokynurenine administered twice a day orally
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Matching capsules of placebo
    Intervention Type
    Drug
    Intervention Name(s)
    AV-101
    Other Intervention Name(s)
    L-4-chlorokynurenine
    Intervention Description
    Oral capsules taken twice daily for 14 days
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Oral capsules taken twice a day for 14 days
    Primary Outcome Measure Information:
    Title
    Unified Dyskinesia Rating Scale
    Description
    (UDysRS) Part 3 AUC
    Time Frame
    14 days
    Title
    Unified Dyskinesia Rating Scale
    Description
    (UDysRS) Part 3 Peak Score
    Time Frame
    14 days
    Secondary Outcome Measure Information:
    Title
    Movement Disorder Society- Unified Parkinson's Disease Rating Scale
    Description
    (MDS-UPDRS) part III (Parkinsonian disability)
    Time Frame
    14 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    30 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female adults, 30 to 80 years of age, inclusive. Diagnosis of idiopathic PD meeting the United Kingdom Parkinson's disease Society Brain Bank criteria. Levodopa-induced dyskinesia present greater than 25% of the day as per MDS-UPDRS. Dyskinesia of at least moderate severity as per MDS-UPDRS Subjects currently receiving anti-parkinsonian medications that contain levodopa and carbidopa are eligible provided they have been on a stable dose of these medications for at least 1 month prior to randomization. Subjects currently receiving antidepressants such as selective serotonin reuptake inhibitors, provided the dose has been stable for at least 1 month prior to randomization. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria: Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is postmenopausal with her last menses at least 1 year prior to screening); or . Childbearing potential, and meets all of the following criteria: i. Women with a negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment. ii. Women who are willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, intrauterine device, sexual abstinence. The form of birth control will be documented at screening. iii. Male partner must use a condom. Exclusion Criteria: Women with childbearing potential who are not willing to use one of the specified forms of birth control during the study or whose partner is unwilling to use a condom. Women who are pregnant or breastfeeding. Women with a positive pregnancy test at screening or baseline. Currently taking a prohibited adjunct therapy such amantadine or monoamine oxidase (MAO) inhibitors must be discontinued at least 3 weeks prior to baseline. Subject had a prior surgery for PD except Deep Brain Stimulation (Deep Brain Stimulation must not have been performed within one year of screening) Hoehn and Yahr score of 5 when "off". Subject with Cognitive impairment and/or history of psychiatric manifestations or active hallucinations. History of positive screening urine test for drugs of abuse at screening: cannabinoids (if the subject has a legitimate medical prescription for cannabis, subject must agree to abstain during the entirety of the study and to have a negative test at baseline), cocaine, barbiturates, opiates. A positive benzodiazepine result will be allowed if there is a valid and prescribed medical use for these agents. For all other positive results, a single re-test is permitted at the judgement of the investigator; results of any retest must be available prior to the baseline visit and must be negative. In poor general health, as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and 12-lead electrocardiogram (ECG).

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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