AV-101 Alone and in Combination With Probenecid in Healthy Subjects

NCT05280054 | Unknown Phase 1 FDA Drug

• 1 other identifier: AV-101 CL005
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, two period, fixed-sequence, drug-drug interaction study to compare the PK and PD of orally administered AV-101 alone and in combination with probenecid in healthy subjects. In Treatment Period 1, subjects will receive AV-101 following an overnight fast of at least 8 hours. In Treatment Period 2, subjects will fast overnight for at least 8 hours, and then receive AV-101 2 hours after receiving 1,000 mg probenecid. Each Treatment Period will be separated by a washout period. The doses of AV-101 in Cohort 1 and a possible Cohort 2 will be 360 mg and 720 mg, respectively. Optional Cohorts 3 and 4 may be enrolled depending on results from Cohorts 1 and 2. CSF will be collected via indwelling catheter to determine the PK of AV-101 and its active metabolite 7-Cl-KYNA.

Conditions

Drug Drug Interaction

Outcome Measures

Primary Outcomes (2)

• Plasma and CSF concentrations of 7-chloro-kynurenic acid (7-Cl-KYNA) in ng/ml

  Difference in 7-Cl-KYNA levels after AV-101 with and without probenecid

  24 hours

• Plasma and CSF concentrations of 4-chloro-kynurenine (AV-101) in ng/ml

  Difference in 4-Cl-KYN levels after AV-101 with and without probenecid

  24 hours

Study Arms (2)

AV-101

EXPERIMENTAL

AV-101 360 mg oral capsules single dose

Drug: AV-101

AV-101 + Probenecid

EXPERIMENTAL

AV-101 360 mg oral capsules + 1000 mg Probenecid

Drug: AV-101; Drug: Probenecid

Interventions

AV-101 DRUG

360 mg capsules

Also known as: 4-chloro-kynurenine

AV-101; AV-101 + Probenecid

Probenecid DRUG

1000 mg oral

AV-101 + Probenecid

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must be a male or non-pregnant, non-breastfeeding female.
• Subject must be between 18 and 55 years of age (inclusive) at the Screening Visit.
• The subject has a body mass index (BMI) between 18.5 kg/m2 and 30 kg/m2 inclusive, with a minimal body weight of 60 kg.
• Female subjects must agree to use double barrier contraception (condom for male partner) and the female using an acceptable form of birth control from screening until 14 days after completion of the study.
• Subject is willing and able to remain in the clinic research unit for the entire duration of each confinement period.
• Subject must be clinically healthy, as assessed by the Investigator, to participate in the study, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead electrocardiogram (ECG), and vital sign measurements performed at the Screening Visit and Admission. Repeat assessment may be performed at the Screening Visit

You may not qualify if:

• Subject on over-the-counter, herbal and prescription medications as well as investigational medicinal products (IMP)s and not completing 14 days or 5 half-lives whichever is longer at the time of screening should be excluded.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
• Has a clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening that in the opinion of the Investigator would preclude the subject from safely participating in the trial.-
• Is a female with a positive pregnancy test result.
• Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methylenedioxymethamphetamine, oxycodone, phencyclidine, tricyclic antidepressants, propoxyphene, and opiates).
• Has a positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or Human Immunodeficiency Virus (HIV) at screening or has been previously treated for Hepatitis B, Hepatitis C, or HIV infection.
• Subject with a QT interval corrected for heart rate using Fridericia's correction (QTcF) greater than 450 ms (males) or greater than 470 ms (females), at screening obtained after at least 5 minutes rest in a supine position using the ECG machine algorithm.
• Subject with a history of allergic reaction to probenecid.
• History of suicide behavior and ideation. At screening, if the C-SSRS responses ("yes" answers to item 4 or 5) indicate that the subject may have experienced suicidal ideation associated with actual intent or plan within 12 months of screening, may have had a history of suicidal behavior within the past 10 years, or had any lifetime history of recurrent suicidal behavior, the subject will be excluded from participation in the study.
• Subject who has a positive reverse transcription polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 \[COVID-19\]) during the Screening or a positive Rapid Swab test for SARS-CoV-2 at Admission.
• Subject who has clinical signs and symptoms consistent with SARS-CoV-2 infection, e.g., fever, dry cough, dyspnea, sore throat, fatigue, or positive SARS-CoV-2 test result within 14 days prior to the Screening Visit or at Admission.
• Subject who had a severe course of SARS-CoV-2 (extracorporeal membrane oxygenation, mechanically ventilated).
• Subject who has recent (within 14 days prior to the Screening Visit or between the Screening Visit and the Admission) exposure to someone who has SARS-CoV-2 symptoms or positive test result.
• Hypersensitivity to anesthetic or derivatives used during CSF collection or any medication used to prepare the area of the lumbar puncture (LP).
• Previous CSF collection within 30 days prior to admission (Day -1) to the clinic research unit.

Sponsors & Collaborators

• VistaGen Therapeutics, Inc.: lead
• Parexel: collaborator

Study Sites (1)

Parexel Early Phase Clinical Unit

Glendale, California, 91206, United States

RECRUITING

MeSH Terms

Interventions

4-chlorokynurenine; Probenecid

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Central Study Contacts

Parexel Phase 1 Unit

CONTACT

888-228-7495; study.losangeles@parexel.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: AV-101 alone followed by AV-101 + Probenecid

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: March 15, 2022
• Study Start: December 23, 2021
• Primary Completion: September 1, 2022
• Study Completion: November 1, 2022
• Last Updated: March 15, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)