- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05280054
AV-101 Alone and in Combination With Probenecid in Healthy Subjects
March 3, 2022 updated by: VistaGen Therapeutics, Inc.
An Open-label, Drug Interaction Study to Evaluate Safety, Pharmacokinetic, and Pharmacodynamic Effect of Oral Administration of AV-101 Alone and in Combination With Probenecid in Healthy Subjects
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Parexel Phase 1 Unit
- Phone Number: 888-228-7495
- Email: study.losangeles@parexel.com
Study Locations
-
-
California
-
Glendale, California, United States, 91206
- Recruiting
- PAREXEL Early Phase Clinical Unit
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- History of vertebral deformities, major lumbar back surgery, clinically significant back pain, clinically significant abnormal X-ray, and/or injury, in the opinion of the Investigator that would preclude the subject participation or CSF collection during study not possible.
- An ongoing skin infection at the LP site.
- Clinically significant coagulation tests values outside the normal reference range (prothrombin time/international normalized ratio, partial thromboplastin time) at screening per Principal Investigator discretion.
- Evidence of disease within 4 weeks before dosing related to chronic headache, migraines, joint pain or other disorders or disease resulting in chronic or intermittent pain.
- Any personal or family history of seizure (including febrile seizures) or diagnosis of epilepsy or episode of unexplained loss of consciousness.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NON_RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: AV-101
AV-101 360 mg oral capsules single dose
|
360 mg capsules
Other Names:
|
EXPERIMENTAL: AV-101 + Probenecid
AV-101 360 mg oral capsules + 1000 mg Probenecid
|
360 mg capsules
Other Names:
1000 mg oral
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma and CSF concentrations of 7-chloro-kynurenic acid (7-Cl-KYNA) in ng/ml
Time Frame: 24 hours
|
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
Time Frame: 24 hours
|
Difference in 4-Cl-KYN levels after AV-101 with and without probenecid
|
24 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
December 23, 2021
Primary Completion (ANTICIPATED)
September 1, 2022
Study Completion (ANTICIPATED)
November 1, 2022
Study Registration Dates
First Submitted
December 27, 2021
First Submitted That Met QC Criteria
March 3, 2022
First Posted (ACTUAL)
March 15, 2022
Study Record Updates
Last Update Posted (ACTUAL)
March 15, 2022
Last Update Submitted That Met QC Criteria
March 3, 2022
Last Verified
December 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AV-101 CL005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Drug Drug Interaction
-
Hutchison Medipharma LimitedCompletedFood-drug Interaction | Drug InteractionUnited States
-
University of Southern CaliforniaRecruitingDrug Drug InteractionUnited States
-
Daewoong Pharmaceutical Co. LTD.Active, not recruitingDrug Drug InteractionKorea, Republic of
-
Daewoong Pharmaceutical Co. LTD.Enrolling by invitationDrug-drug InteractionKorea, Republic of
-
Daewoong Pharmaceutical Co. LTD.CompletedDrug Drug InteractionKorea, Republic of
-
ItalfarmacoCompletedDrug-Drug InteractionPortugal
-
Aurinia Pharmaceuticals Inc.CompletedDrug-drug InteractionUnited States
-
Blade TherapeuticsCompletedDrug Drug InteractionUnited States
-
Daewoong Pharmaceutical Co. LTD.CompletedDrug-drug InteractionAustralia
-
Nanjing Yoko Biomedical Co., Ltd.CompletedDrug-drug InteractionChina
Clinical Trials on AV-101
-
Marijn Lijffijt, PhDMichael E. DeBakey VA Medical Center; VistaGen Therapeutics, Inc.Completed
-
Aerovate TherapeuticsActive, not recruitingPulmonary Arterial HypertensionUnited States, Belgium, Spain, Australia, Canada, Singapore, China, Germany, Latvia, Italy, United Kingdom, Portugal, France, Mexico, Argentina, Poland, Chile, Israel, South Africa, Colombia
-
Aerovate TherapeuticsActive, not recruitingPulmonary Arterial HypertensionGermany, United States, Belgium, Spain, Australia, Israel, Canada, Singapore, China, Latvia, Italy, Sweden, France, United Kingdom, Austria, Czechia, Netherlands, Poland, Mexico, Puerto Rico, Brazil, Portugal, Argentina, Chile, Greece, South...
-
VistaGen Therapeutics, Inc.CompletedMajor Depressive DisorderUnited States
-
VistaGen Therapeutics, Inc.Not yet recruitingParkinson Disease | Dyskinesia, Medication-Induced | L-Dopa Causing Adverse Effects in Therapeutic Use
-
VistaGen Therapeutics, Inc.National Institute on Drug Abuse (NIDA); Cato ResearchCompletedNeuropathic PainUnited States
-
National Institute of Mental Health (NIMH)CompletedMajor DepressionUnited States
-
University Hospital, Gentofte, CopenhagenRigshospitalet, Denmark; Lund University HospitalUnknownHeart Failure | Ischemic CardiomyopathyDenmark, Sweden
-
Northwestern UniversityNational Institute on Aging (NIA)RecruitingPrimary Progressive Aphasia With Suspected Alzheimer's DiseaseUnited States
-
Columbia UniversityNational Institute of Neurological Disorders and Stroke (NINDS)CompletedTauopathies | Frontotemporal Dementia (FTD) | Frontotemporal Lobar Degeneration (FTLD)United States