Trial Outcomes & Findings for Electrophysiological Biomarkers of AV-101 (NCT NCT03583554)

NCT ID: NCT03583554

Last Updated: 2022-02-17

Results Overview

Mean power (in microVolt squared; uV\^2) of 40-Hz Auditory Steady State Response (ASSR; an auditory task using 40Hz click trains) calculated across 38-42Hz. Mean +/- SE across pre-treatment baseline and 4 post-treatment measures one every hour controlled for time, with outcomes the mean per treatment arm obtained from Linear Mixed Model analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: 4 hours
• Results posted on: 2022-02-17

Participant Flow

Participants with eligible if they were between 18 and 64 years old, a US military veteran, and have no history of psychiatric illness.

This is a randomized cross-over design, meaning that all subjects received all doses. Total recruited was 18, and total randomized was 12. Ten subjects completed all study visits.

Participant milestones

Measure	Placebo, Then AV-101 720 mg, Then AV-101 1440 mg Participants first received a single dose of oral placebo. After at least 3 days wash-out participants got a single dose of oral AV-101 720mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral AV-101 1440mg (matching placebo capsules).	AV-101 720 mg, Then AV-101 1440 mg, Then Placebo Participants first received a single dose of oral AV-101 720mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral AV-101 1440mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral placebo.	AV-101 1440 mg, Then Placebo Then, AV-101 720 mg Then Participants first received a single dose of oral AV-101 1440mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral placebo. After at least 3 days wash-out participants got a single dose of oral AV-101 720mg (matching placebo capsules).
Period 1 STARTED	4	4	4
Period 1 COMPLETED	4	4	4
Period 1 NOT COMPLETED	0	0	0
Period 2 STARTED	4	4	4
Period 2 COMPLETED	3	4	3
Period 2 NOT COMPLETED	1	0	1
Period 3 STARTED	3	4	3
Period 3 COMPLETED	3	4	3
Period 3 NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Placebo, Then AV-101 720 mg, Then AV-101 1440 mg Participants first received a single dose of oral placebo. After at least 3 days wash-out participants got a single dose of oral AV-101 720mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral AV-101 1440mg (matching placebo capsules).	AV-101 720 mg, Then AV-101 1440 mg, Then Placebo Participants first received a single dose of oral AV-101 720mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral AV-101 1440mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral placebo.	AV-101 1440 mg, Then Placebo Then, AV-101 720 mg Then Participants first received a single dose of oral AV-101 1440mg (matching placebo capsules). After at least 3 days wash-out participants got a single dose of oral placebo. After at least 3 days wash-out participants got a single dose of oral AV-101 720mg (matching placebo capsules).
Period 2 Did not receive treatment due to loss of contact	1	0	1

Baseline Characteristics

Electrophysiological Biomarkers of AV-101

Baseline characteristics by cohort

Measure	All Study Participants n=12 Participants All 12 study participants who started the study
Age, Continuous	31.33 years STANDARD_DEVIATION 6.28 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 hours

Mean power (in microVolt squared; uV^2) of 40-Hz Auditory Steady State Response (ASSR; an auditory task using 40Hz click trains) calculated across 38-42Hz.

Mean +/- SE across pre-treatment baseline and 4 post-treatment measures one every hour controlled for time, with outcomes the mean per treatment arm obtained from Linear Mixed Model analysis.

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Mean 40-Hz Auditory Steady State Response Power	0.34 uV^2 Standard Error 0.11	0.43 uV^2 Standard Error 0.11	0.60 uV^2 Standard Error 0.11

SECONDARY outcome

Timeframe: 4 hours

Assesses the peak change from baseline and corrected for placebo (placebo set at 0) across a 4 hours time frame after drug intake. 4-Chloro-kynurenine is the main ingredient of AV-101 and is a precursor of 7-Chloro-kynurenic acid.

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Peak Change in Plasma Concentration of AV-101 Marker 4-Chloro-kynurenine	0 ng/Ml Standard Deviation 0	28,532 ng/Ml Standard Deviation 21,462	51,450 ng/Ml Standard Deviation 21,182

SECONDARY outcome

Timeframe: 4 hours

Assesses the peak change from baseline and corrected for placebo (placebo set at 0) across a 4 hours time frame after drug intake. 7-Chloro-kynurenic acid is the main metabolite of AV-101 (4-Chloro-kynurenine).

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Peak Change in Plasma Concentration of AV-101 Marker 7-Chloro-kynurenic Acid	0 ng/Ml Standard Deviation 0	93 ng/Ml Standard Deviation 48	412 ng/Ml Standard Deviation 473

SECONDARY outcome

Timeframe: 5 hours

Systolic blood pressure Mean +/- SE averaged across all timepoints (including baseline). Systolic blood pressure was measured 15 minutes before drug intake and every 15 minutes from drug intake until 5 hours after intake controlled for time, with outcomes the mean per treatment arm obtained from Linear Mixed Model analysis.

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Mean Systolic Blood Pressure	122.5 mm Hg Standard Error 2.7	119.6 mm Hg Standard Error 2.7	120.1 mm Hg Standard Error 2.7

SECONDARY outcome

Timeframe: 5 hours

Diastolic blood pressure Mean +/- SE averaged across all timepoints (including baseline). Diastolic blood pressure was measured 15 minutes before drug intake and every 15 minutes from drug intake until 5 hours after intake controlled for time, with outcomes the mean per treatment arm obtained from Linear Mixed Model analysis

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Mean Diastolic Blood Pressure	80.8 mm Hg Standard Error 2.35	79 mm Hg Standard Error 2.35	76.3 mm Hg Standard Error 2.35

SECONDARY outcome

Timeframe: 5 hours

Pulse Mean +/- SE averaged across all timepoints (including baseline). Pulse was measured 15 minutes before drug intake and every 15 minutes from drug intake until 5 hours after intake controlled for time, with outcomes the mean per treatment arm obtained from Linear Mixed Model analysis

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Mean Pulse	68.8 beat per minute (bpm) Standard Error 1.82	70.5 beat per minute (bpm) Standard Error 1.82	69.9 beat per minute (bpm) Standard Error 1.82

SECONDARY outcome

Timeframe: 5 hours

POMS total score Mean +/- SE averaged across all timepoints (including baseline). Systolic blood pressure was measured directly before drug intake and every hours from drug intake until 5 hours after intake controlled for time, with outcomes the mean per treatment arm obtained from Linear Mixed Model analysis

The POMS is a 40 item scale. Each item is scored on a 0 (absent) - 4 (extreme) scale. POMS total score ranges from 0 to 160. Higher scores mean more extreme dysregulated mood. Subscales are tension (6 items; score anger 0-24), depression (6 items, range 0-24), fatigue (5 items, range 0-20), vigor (6 items, range 0-24), confusion (5 items, range 0-20), anger (7 items, range 0-28), and mania-related affect (5 items, range 0-20).

Outcome measures

Measure	Placebo n=10 Participants Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=10 Participants One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=10 Participants One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Mean Profile of Moods Scale Total Score	11.6 Units on a scale Standard Error 1.65	12 Units on a scale Standard Error 1.65	11.6 Units on a scale Standard Error 1.65

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

AV-101 720 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

AV-101 1440 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=12 participants at risk Placebo Placebo: Single dose of 4 placebo oral capsules	AV-101 720 mg n=12 participants at risk One time 720 mg L-4-Chlorokynurenine AV-101 720 mg: Single dose of 2 360 mg AV-101 oral capsules + 2 placebo oral capsules	AV-101 1440 mg n=12 participants at risk One time 1440 mg L-4-Chlorokynurenine AV-101 1440 mg: Single dose of 4 360 mg AV-101 oral capsules
Gastrointestinal disorders diarrhea	0.00% 0/12 • 24 hours Asked by study team if experiencing any health complications last 24 hours since study intake. Any health complications not related to the study medication were also asked about when subjects at study visits from the moment that they were enrolled in the study until they had completed the study.	0.00% 0/12 • 24 hours Asked by study team if experiencing any health complications last 24 hours since study intake. Any health complications not related to the study medication were also asked about when subjects at study visits from the moment that they were enrolled in the study until they had completed the study.	8.3% 1/12 • Number of events 1 • 24 hours Asked by study team if experiencing any health complications last 24 hours since study intake. Any health complications not related to the study medication were also asked about when subjects at study visits from the moment that they were enrolled in the study until they had completed the study.
Nervous system disorders Elation	0.00% 0/12 • 24 hours Asked by study team if experiencing any health complications last 24 hours since study intake. Any health complications not related to the study medication were also asked about when subjects at study visits from the moment that they were enrolled in the study until they had completed the study.	8.3% 1/12 • Number of events 1 • 24 hours Asked by study team if experiencing any health complications last 24 hours since study intake. Any health complications not related to the study medication were also asked about when subjects at study visits from the moment that they were enrolled in the study until they had completed the study.	0.00% 0/12 • 24 hours Asked by study team if experiencing any health complications last 24 hours since study intake. Any health complications not related to the study medication were also asked about when subjects at study visits from the moment that they were enrolled in the study until they had completed the study.

Additional Information

Dr. Marijn Lijffijt, Assistant Professorq

Baylor College of Medicine and Michael E. DeBakey VA Medical Center

Phone: 713-798-5642

Email: marijn.lijffijt@bcm.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place