Trial Outcomes & Findings for Antidepressant Effects of the Glycine Receptor Antagonist AV-101 (4-chlorokynurenine) in Major Depressive Disorder (NCT NCT02484456)
NCT ID: NCT02484456
Last Updated: 2022-04-11
Results Overview
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
COMPLETED
PHASE2
22 participants
Post Dose Day 0
2022-04-11
Participant Flow
22 participants signed consent. 3 participants withdrew before start of treatment leaving 19 participants starting.
Participant milestones
| Measure |
AV 101 (4-chlorokynurenine), Then Placebo
After a two-week drug-free period, participants received daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,080mg/day for seven days, then dose increased to AV 101 1,440mg/day for next seven days followed by a two-week washout period; then crossover to placebo phase with daily dose of placebo pill for two weeks.
|
Placebo, Then AV 101 (4-chlorokynurenine)
After a two-week drug-free period, participants received daily dose of placebo pill for two weeks followed by two-week washout period; then crossover to AV 101 (4-chlorokynurenine) treatment phase with daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then dose increased to AV 101 1,440mg/day for next seven days.
|
|---|---|---|
|
First Treatment Period: Week 1
STARTED
|
10
|
9
|
|
First Treatment Period: Week 1
COMPLETED
|
10
|
9
|
|
First Treatment Period: Week 1
NOT COMPLETED
|
0
|
0
|
|
First Treatment Period: Week 2
STARTED
|
10
|
9
|
|
First Treatment Period: Week 2
COMPLETED
|
10
|
9
|
|
First Treatment Period: Week 2
NOT COMPLETED
|
0
|
0
|
|
Washout Period
STARTED
|
10
|
9
|
|
Washout Period
COMPLETED
|
10
|
8
|
|
Washout Period
NOT COMPLETED
|
0
|
1
|
|
Second Treatment Period: Week 1
STARTED
|
10
|
8
|
|
Second Treatment Period: Week 1
COMPLETED
|
9
|
7
|
|
Second Treatment Period: Week 1
NOT COMPLETED
|
1
|
1
|
|
Second Treatment Period: Week 2
STARTED
|
9
|
7
|
|
Second Treatment Period: Week 2
COMPLETED
|
9
|
6
|
|
Second Treatment Period: Week 2
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
AV 101 (4-chlorokynurenine), Then Placebo
After a two-week drug-free period, participants received daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,080mg/day for seven days, then dose increased to AV 101 1,440mg/day for next seven days followed by a two-week washout period; then crossover to placebo phase with daily dose of placebo pill for two weeks.
|
Placebo, Then AV 101 (4-chlorokynurenine)
After a two-week drug-free period, participants received daily dose of placebo pill for two weeks followed by two-week washout period; then crossover to AV 101 (4-chlorokynurenine) treatment phase with daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then dose increased to AV 101 1,440mg/day for next seven days.
|
|---|---|---|
|
Washout Period
Withdrawal by Subject
|
0
|
1
|
|
Second Treatment Period: Week 1
Adverse Event
|
1
|
0
|
|
Second Treatment Period: Week 1
Withdrawal by Subject
|
0
|
1
|
|
Second Treatment Period: Week 2
Adverse Event
|
0
|
1
|
Baseline Characteristics
Antidepressant Effects of the Glycine Receptor Antagonist AV-101 (4-chlorokynurenine) in Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
AV 101 (4-chlorokynurenine), Then Placebo
n=10 Participants
After a two-week drug-free period, participants received daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,080mg/day for seven days, then dose increased to AV 101 1,440mg/day for next seven days followed by a two-week washout period; then crossover to placebo phase with daily dose of placebo pill for two weeks.
|
Placebo, Then AV 101 (4-chlorokynurenine)
n=9 Participants
After a two-week drug-free period, participants received daily dose of placebo pill for two weeks followed by two-week washout period; then crossover to AV 101 (4-chlorokynurenine) treatment phase with daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then dose increased to AV 101 1,440mg/day for next seven days.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Post Dose Day 0Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Depression Rating Score
|
20.22 score on a scale
Standard Error 0.68
|
20.56 score on a scale
Standard Error 0.51
|
PRIMARY outcome
Timeframe: Post Dose Day 1Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Depression Rating Score
|
20.22 score on a scale
Standard Error 0.58
|
20.06 score on a scale
Standard Error 0.52
|
PRIMARY outcome
Timeframe: Post Dose Day 2Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Depression Rating Score
|
20.75 score on a scale
Standard Error 0.62
|
20.41 score on a scale
Standard Error 0.71
|
PRIMARY outcome
Timeframe: Post Dose Day 3Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Depression Rating Score
|
19.51 score on a scale
Standard Error 0.72
|
20.74 score on a scale
Standard Error 0.83
|
PRIMARY outcome
Timeframe: Post Dose Day 7Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Depression Rating Score
|
21.28 score on a scale
Standard Error 0.70
|
20.43 score on a scale
Standard Error 1.10
|
PRIMARY outcome
Timeframe: Post Dose Day 13Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Depression Rating scale is a 17-item global measure of depressive symptoms on a 5-point scale ranging from 0 = not present to 4 = severe (full score values = 0,1,2,3,4). Some items rated on a scale of 0-2 (0, 1, 2) with 0 = not present to 2 = more severe. Total scores are a sum of the individual items. The maximum total score being 52 on the 17-point scale, and the minimum score being 0.Total scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Depression Rating Score
|
21.52 score on a scale
Standard Error 1.13
|
19.69 score on a scale
Standard Error 1.13
|
SECONDARY outcome
Timeframe: Post Dose Day 0Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Beck Depression Inventory (BDI) is a 21-item measure of depression with each question on a 4-point scale ranging from 0=minimal to 3 = more severe (full list score values = 0,1,2,3). Total scores are a sum of individual items. The minimal depression = 0-13, mild depression = 14-19, moderate depression = 20-28, and severe depression = 29-63. The maximum score being 63 and the minimum possible score = 0.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Beck Depression Score
|
25.35 score on a scale
Standard Error 0.79
|
25.79 score on a scale
Standard Error 0.63
|
SECONDARY outcome
Timeframe: Post Dose Day 1Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Beck Depression Inventory (BDI) is a 21-item measure of depression with each question on a 4-point scale ranging from 0=minimal to 3 = more severe (full list score values = 0,1,2,3). Total scores are a sum of individual items. The minimal depression = 0-13, mild depression = 14-19, moderate depression = 20-28, and severe depression = 29-63. The maximum score being 63 and the minimum possible score = 0.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Beck Depression Score
|
24.76 score on a scale
Standard Error 0.84
|
24.75 score on a scale
Standard Error 1.04
|
SECONDARY outcome
Timeframe: Post Dose Day 2Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Beck Depression Inventory (BDI) is a 21-item measure of depression with each question on a 4-point scale ranging from 0=minimal to 3 = more severe (full list score values = 0,1,2,3). Total scores are a sum of individual items. The minimal depression = 0-13, mild depression = 14-19, moderate depression = 20-28, and severe depression = 29-63. The maximum score being 63 and the minimum possible score = 0.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Beck Depression Score
|
25.88 score on a scale
Standard Error 0.67
|
26.14 score on a scale
Standard Error 0.99
|
SECONDARY outcome
Timeframe: Post Dose Day 3Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Beck Depression Inventory (BDI) is a 21-item measure of depression with each question on a 4-point scale ranging from 0=minimal to 3 = more severe (full list score values = 0,1,2,3). Total scores are a sum of individual items. The minimal depression = 0-13, mild depression = 14-19, moderate depression = 20-28, and severe depression = 29-63. The maximum score being 63 and the minimum possible score = 0.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Beck Depression Score
|
25.64 score on a scale
Standard Error 0.69
|
24.64 score on a scale
Standard Error 1.35
|
SECONDARY outcome
Timeframe: Post Dose Day 7Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Beck Depression Inventory (BDI) is a 21-item measure of depression with each question on a 4-point scale ranging from 0=minimal to 3 = more severe (full list score values = 0,1,2,3). Total scores are a sum of individual items. The minimal depression = 0-13, mild depression = 14-19, moderate depression = 20-28, and severe depression = 29-63. The maximum score being 63 and the minimum possible score = 0.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Beck Depression Score
|
25.82 score on a scale
Standard Error 1.13
|
24.22 score on a scale
Standard Error 1.35
|
SECONDARY outcome
Timeframe: Post Dose Day 13Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Beck Depression Inventory (BDI) is a 21-item measure of depression with each question on a 4-point scale ranging from 0=minimal to 3 = more severe (full list score values = 0,1,2,3). Total scores are a sum of individual items. The minimal depression = 0-13, mild depression = 14-19, moderate depression = 20-28, and severe depression = 29-63. The maximum score being 63 and the minimum possible score = 0.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Beck Depression Score
|
25.86 score on a scale
Standard Error 1.09
|
23.84 score on a scale
Standard Error 1.55
|
SECONDARY outcome
Timeframe: Post Dose Day 0Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item global measure of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe) (full score list = 0,1,2,3,4), with a total score range of 0-56 (0 = minimum score and 56 = maximum), where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores are a sum of individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Anxiety Rating Score
|
15.71 score on a scale
Standard Error 0.56
|
16.20 score on a scale
Standard Error 0.72
|
SECONDARY outcome
Timeframe: Post Dose Day 1Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item global measure of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe) (full score list = 0,1,2,3,4), with a total score range of 0-56 (0 = minimum score and 56 = maximum), where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores are a sum of individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Anxiety Rating Score
|
17.30 score on a scale
Standard Error 0.61
|
16.67 score on a scale
Standard Error 0.75
|
SECONDARY outcome
Timeframe: Post Dose Day 2Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item global measure of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe) (full score list = 0,1,2,3,4), with a total score range of 0-56 (0 = minimum score and 56 = maximum), where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores are a sum of individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Anxiety Rating Score
|
17.83 score on a scale
Standard Error 0.55
|
17.66 score on a scale
Standard Error 0.94
|
SECONDARY outcome
Timeframe: Post Dose Day 3Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item global measure of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe) (full score list = 0,1,2,3,4), with a total score range of 0-56 (0 = minimum score and 56 = maximum), where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores are a sum of individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Anxiety Rating Score
|
16.48 score on a scale
Standard Error 0.65
|
17.87 score on a scale
Standard Error 0.62
|
SECONDARY outcome
Timeframe: Post Dose Day 7Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item global measure of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe) (full score list = 0,1,2,3,4), with a total score range of 0-56 (0 = minimum score and 56 = maximum), where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores are a sum of individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Anxiety Rating Score
|
18.42 score on a scale
Standard Error 0.74
|
17.25 score on a scale
Standard Error 1.06
|
SECONDARY outcome
Timeframe: Post Dose Day 13Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item global measure of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe) (full score list = 0,1,2,3,4), with a total score range of 0-56 (0 = minimum score and 56 = maximum), where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores are a sum of individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Hamilton Anxiety Rating Score
|
18.33 score on a scale
Standard Error 0.81
|
16.28 score on a scale
Standard Error 0.97
|
SECONDARY outcome
Timeframe: Post Dose Day 0Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item global measure evaluating core symptoms of depression. Questions concern how the patient has felt over the past week. Each item is rated on a scale from 0 to 6, with 0 being "normal/not present" and 6 being "extreme" (full score list = 0,1,2,3,4,5,6). Maximum score = 60, minimum score = 0. Total scores are a sum of the individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Montgomery-Asberg Depression Rating Score
|
29.28 score on a scale
Standard Error 0.62
|
29.48 score on a scale
Standard Error 0.76
|
SECONDARY outcome
Timeframe: Post Dose Day 1Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item global measure evaluating core symptoms of depression. Questions concern how the patient has felt over the past week. Each item is rated on a scale from 0 to 6, with 0 being "normal/not present" and 6 being "extreme" (full score list = 0,1,2,3,4,5,6). Maximum score = 60, minimum score = 0. Total scores are a sum of the individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Montgomery-Asberg Depression Rating Score
|
28.75 score on a scale
Standard Error 0.63
|
28.79 score on a scale
Standard Error 1.06
|
SECONDARY outcome
Timeframe: Post Dose Day 2Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item global measure evaluating core symptoms of depression. Questions concern how the patient has felt over the past week. Each item is rated on a scale from 0 to 6, with 0 being "normal/not present" and 6 being "extreme" (full score list = 0,1,2,3,4,5,6). Maximum score = 60, minimum score = 0. Total scores are a sum of the individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Montgomery-Asberg Depression Rating Score
|
29.51 score on a scale
Standard Error 0.48
|
29.84 score on a scale
Standard Error 1.30
|
SECONDARY outcome
Timeframe: Post Dose Day 3Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item global measure evaluating core symptoms of depression. Questions concern how the patient has felt over the past week. Each item is rated on a scale from 0 to 6, with 0 being "normal/not present" and 6 being "extreme" (full score list = 0,1,2,3,4,5,6). Maximum score = 60, minimum score = 0. Total scores are a sum of the individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Montgomery-Asberg Depression Rating Score
|
29.85 score on a scale
Standard Error 0.71
|
30.81 score on a scale
Standard Error 1.10
|
SECONDARY outcome
Timeframe: Post Dose Day 7Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item global measure evaluating core symptoms of depression. Questions concern how the patient has felt over the past week. Each item is rated on a scale from 0 to 6, with 0 being "normal/not present" and 6 being "extreme" (full score list = 0,1,2,3,4,5,6). Maximum score = 60, minimum score = 0. Total scores are a sum of the individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Montgomery-Asberg Depression Rating Score
|
30.45 score on a scale
Standard Error 0.89
|
28.64 score on a scale
Standard Error 1.67
|
SECONDARY outcome
Timeframe: Post Dose Day 13Population: The primary analysis compared active drug condition with placebo condition. Using within subject data (each person serving as their own control), we estimated means for drug, placebo and their difference at each time point. If outcome data were missing subsequent to a participant dropping out, their available data was included in the model.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item global measure evaluating core symptoms of depression. Questions concern how the patient has felt over the past week. Each item is rated on a scale from 0 to 6, with 0 being "normal/not present" and 6 being "extreme" (full score list = 0,1,2,3,4,5,6). Maximum score = 60, minimum score = 0. Total scores are a sum of the individual items.
Outcome measures
| Measure |
AV 101 (4-chlorokynurenine)
n=19 Participants
Participants received daily oral dose of AV 101 monotherapy 1,080mg/day for seven days, then 1,440mg/day for next seven days.
|
Placebo
n=19 Participants
Participants received a daily oral dose of placebo pills for 2 weeks.
|
|---|---|---|
|
Model Adjusted Means for Montgomery-Asberg Depression Rating Score
|
29.70 score on a scale
Standard Error 1.05
|
27.06 score on a scale
Standard Error 1.25
|
Adverse Events
AV 101 (4-chlorokynurenine) 1,080 mg for 1 Week
AV 101 (4-chlorokynurenine) 1,440 mg for 1 Week
Placebo 2 Weeks
Serious adverse events
| Measure |
AV 101 (4-chlorokynurenine) 1,080 mg for 1 Week
n=19 participants at risk
Daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,080mg/day for seven days
|
AV 101 (4-chlorokynurenine) 1,440 mg for 1 Week
n=19 participants at risk
Daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,440 mg/day for seven days
|
Placebo 2 Weeks
n=19 participants at risk
Daily dose of placebo pill for two weeks
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Cerebrospinal fluid leakage
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
Other adverse events
| Measure |
AV 101 (4-chlorokynurenine) 1,080 mg for 1 Week
n=19 participants at risk
Daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,080mg/day for seven days
|
AV 101 (4-chlorokynurenine) 1,440 mg for 1 Week
n=19 participants at risk
Daily oral dose of AV 101 (4-chlorokynurenine) monotherapy 1,440 mg/day for seven days
|
Placebo 2 Weeks
n=19 participants at risk
Daily dose of placebo pill for two weeks
|
|---|---|---|---|
|
Cardiac disorders
Chest pain
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Eye disorders
Eye irritation
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Eye disorders
Vision blurred
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
10.5%
2/19 • 3 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
General disorders
Cold sweat
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
General disorders
Decreased appetite
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
General disorders
Fatigue
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
General disorders
Irritability
|
10.5%
2/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
General disorders
Pyrexia
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
15.8%
3/19 • 3 months
|
0.00%
0/19 • 3 months
|
15.8%
3/19 • 3 months
|
|
Nervous system disorders
Advanced sleep phase
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
10.5%
2/19 • 3 months
|
|
Nervous system disorders
Headache
|
26.3%
5/19 • 3 months
|
0.00%
0/19 • 3 months
|
15.8%
3/19 • 3 months
|
|
Nervous system disorders
Insomnia
|
15.8%
3/19 • 3 months
|
0.00%
0/19 • 3 months
|
10.5%
2/19 • 3 months
|
|
Nervous system disorders
Memory impairment
|
10.5%
2/19 • 3 months
|
5.3%
1/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Nervous system disorders
Motor dysfunction
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
10.5%
2/19 • 3 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Nervous system disorders
Sedation
|
15.8%
3/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Nervous system disorders
Sensory loss
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
10.5%
2/19 • 3 months
|
|
Nervous system disorders
Sleep phase rhythm disturbance
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Nervous system disorders
Tremor
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Infections and infestations
Influenza
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Gastrointestinal disorders
Pharyngitis
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
Gastrointestinal disorders
Reflux gastritis
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
0.00%
0/19 • 3 months
|
|
General disorders
Asthenia
|
0.00%
0/19 • 3 months
|
5.3%
1/19 • 3 months
|
0.00%
0/19 • 3 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place