Drug Drug InteractionPhase 1NCT05280054
AV-101 Alone and in Combination With Probenecid in Healthy Subjects
A Phase 1 study testing AV-101 and Probenecid in people with Drug Drug Interaction, run by VistaGen Therapeutics, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Drug Interaction
- What is being tested?
- AV-101 and Probenecid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Dec 2021to 1 Nov 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Parexel Early Phase Clinical Unit
Glendale, California, 91206
About this study
Official title: 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.
- Conditions
- Drug Drug Interaction
- Being tested
- AV-101, Probenecid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AV-101Drug
Also called 4-chloro-kynurenine
360 mg capsules
ProbenecidDrug
1000 mg oral
| Study group | Role | What they receive |
|---|---|---|
| AV-101 | Experimental | AV-101 360 mg oral capsules single dose Receives: Drug: AV-101 |
| AV-101 + Probenecid | Experimental | AV-101 360 mg oral capsules + 1000 mg Probenecid Receives: Drug: AV-101; Drug: Probenecid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start23 Dec 2021
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Drug InteractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- AV-101 alone followed by AV-101 + Probenecid
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VistaGen Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05280054
- Sponsor's protocol ID
- AV-101 CL005
- Status last verified
- Dec 2021
- First submitted
- 27 Dec 2021
- Last updated
- 15 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05280054
- Acronym / sponsor ID
- AV-101 CL005
- Conditions
- Drug Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- VistaGen Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 23 Dec 2021 (actual)
- Primary completion
- 1 Sep 2022 (estimated)
- Study completion
- 1 Nov 2022 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- AV-101 alone followed by AV-101 + Probenecid
| Arm | Type | Receives |
|---|---|---|
| AV-101 | Experimental | Drug: AV-101AV-101 360 mg oral capsules single dose |
| AV-101 + Probenecid | Experimental | Drug: AV-101, Drug: ProbenecidAV-101 360 mg oral capsules + 1000 mg Probenecid |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (20 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AV-101Also: 4-chloro-kynurenine360 mg capsules | Drug | AV-101, AV-101 + Probenecid |
| Probenecid1000 mg oral | Drug | AV-101 + Probenecid |
Primary outcome
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AV-101 and Probenecid in people with Drug Drug Interaction, run by VistaGen Therapeutics, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Parexel Phase 1 Unit (888-228-7495, study.losangeles@parexel.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma and CSF concentrations of 7-chloro-kynurenic acid (7-Cl-KYNA) in ng/ml (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.