Trial Outcomes & Findings for Translating Metabolic Responses to Mechanical Insult Into Early Interventions to Prevent PTOA (NCT NCT04589611)
NCT ID: NCT04589611
Last Updated: 2026-07-06
Results Overview
Safety Measures: CBC and standard clinical chemistry assays to quantify circulating, ALT, AST, Bilirubin, Creatinine, and BUN and the measurement of urine protein content will be evaluated and the number of participants with clinically significant abnormal laboratory values will be determined. Presence of amobarbital will be tested in blood and urine samples and the number of subjects it is detected in will be reported.
TERMINATED
PHASE1/PHASE2
5 participants
Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op.]
2026-07-06
Participant Flow
Participant milestones
| Measure |
Phase I Single Amobarbital/Gel-One Dose
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
Phase IIa Part 1 Amobarbital/Gel-One Dose
20 subjects will be randomized to amobarbital/Gel-One single dose.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
Phase IIa Part 1 Placebo
10 subjects will be randomized to amobarbital/Gel-One single dose.
Placebo (single dose): One dose of placebo during the initial surgical intervention
|
Phase IIa Part 2 Amobarbital/Gel-One Dose
20 subjects will be randomized to one dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
amobarbital/Gel-One (two doses): One dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
|
Phase IIa Part 2 Placebo
20 subjects will be randomized to one dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
Placebo (two doses): One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
0
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
3
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Phase I Single Amobarbital/Gel-One Dose
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
Phase IIa Part 1 Amobarbital/Gel-One Dose
20 subjects will be randomized to amobarbital/Gel-One single dose.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
Phase IIa Part 1 Placebo
10 subjects will be randomized to amobarbital/Gel-One single dose.
Placebo (single dose): One dose of placebo during the initial surgical intervention
|
Phase IIa Part 2 Amobarbital/Gel-One Dose
20 subjects will be randomized to one dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
amobarbital/Gel-One (two doses): One dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
|
Phase IIa Part 2 Placebo
20 subjects will be randomized to one dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
Placebo (two doses): One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
|
|---|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Translating Metabolic Responses to Mechanical Insult Into Early Interventions to Prevent PTOA
Baseline characteristics by cohort
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
Phase IIa Part 1 Amobarbital/Gel-One Dose
20 subjects will be randomized to amobarbital/Gel-One single dose.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
Phase IIa Part 1 Placebo
10 subjects will be randomized to amobarbital/Gel-One single dose.
Placebo (single dose): One dose of placebo during the initial surgical intervention
|
Phase IIa Part 2 Amobarbital/Gel-One Dose
20 subjects will be randomized to one dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
amobarbital/Gel-One (two doses): One dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
|
Phase IIa Part 2 Placebo
20 subjects will be randomized to one dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
Placebo (two doses): One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
5 Participants
n=22 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Age, Continuous
|
39.6 years
STANDARD_DEVIATION 13.4 • n=9 Participants
|
—
|
—
|
—
|
—
|
39.6 years
STANDARD_DEVIATION 13.4 • n=22 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
3 Participants
n=22 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
2 Participants
n=22 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
5 Participants
n=22 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
0 Participants
n=22 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=9 Participants
|
—
|
—
|
—
|
—
|
5 Participants
n=22 Participants
|
|
BMI
|
30.3 kg/m2
STANDARD_DEVIATION 7.1 • n=9 Participants
|
—
|
—
|
—
|
—
|
30.3 kg/m2
STANDARD_DEVIATION 7.1 • n=22 Participants
|
PRIMARY outcome
Timeframe: Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op.]Safety Measures: CBC and standard clinical chemistry assays to quantify circulating, ALT, AST, Bilirubin, Creatinine, and BUN and the measurement of urine protein content will be evaluated and the number of participants with clinically significant abnormal laboratory values will be determined. Presence of amobarbital will be tested in blood and urine samples and the number of subjects it is detected in will be reported.
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically
Amobarbital Detected - Urine
|
0 Participants
|
|
Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically
Amobarbital Detected - Serum
|
0 Participants
|
|
Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically
Abnormal Chemistry Panel
|
0 Participants
|
|
Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically
Abnormal CBC Result
|
0 Participants
|
|
Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically
Abnormal Urine Protein
|
0 Participants
|
PRIMARY outcome
Timeframe: Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op.Population: Samples were not taken and this measurement was not completed
Local toxicity will be determined by examining the osteochondral fragments obtained during the internal fixation surgery for cartilage and synovial histological changes. This outcome was discontinued. Samples were not taken and this measurement was not completed.
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
Determine the Number of Participants With a Change of Local Toxicity in Tissues. (Outcome Discontinued)
|
0 Participants
|
SECONDARY outcome
Timeframe: 3, 6, 12, and 24 monthsPopulation: Only 1 participant had completed PROMIS PI at the 12 month follow-up visit, and none completed this for the 24 month follow-up visit.
Pain Interference scale. Higher scores indicate greater pain interference (worse score). Result is reported as a T-score, with the population norm at 50 and a standard deviation of 10.
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) - Pain Interference
Month 3
|
50.5 t-score
Standard Deviation 8.2
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) - Pain Interference
Month 6
|
55.4 t-score
Standard Deviation 6.6
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) - Pain Interference
Month 12
|
54.6 t-score
there is only 1 subject, so there is no standard deviation
|
SECONDARY outcome
Timeframe: 3, 6, 12 and 24 month follow-up visitPopulation: Only one participant completed PROMIS - Physical Function at 12 month follow-up and none have completed it at a 24 month follow-up visit.
Physical Function - T-score - mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. Higher is better.
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Physical Function
Month 12
|
49.9 score on a scale
Standard Deviation 0
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Physical Function
Month 6
|
44.8 score on a scale
Standard Deviation 5.9
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Physical Function
Month 3
|
39.0 score on a scale
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: 6, 12 and 24 month follow-upPopulation: Only one participant completed PROMIS Global Health Questionnaire at 12 month follow-up visit, and none completed it at 24 month visit. Higher scores are better
Global Health - T-score - mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. Higher is better.
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Global Health Questionnaires - Mental Health and Physical Health Scores
Mental Health Month 6
|
54.2 score on a scale
Standard Deviation 8.1
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Global Health Questionnaires - Mental Health and Physical Health Scores
Physical Health Month 6
|
45.2 score on a scale
Standard Deviation 5.3
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Global Health Questionnaires - Mental Health and Physical Health Scores
Mental Health Month 12
|
62.5 score on a scale
Standard Deviation 0
|
|
Patient Reported Outcome Measurement Information Systems (PROMIS) Global Health Questionnaires - Mental Health and Physical Health Scores
Physical Health Month 12
|
50.8 score on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 6,12 and 24 month follow-upPopulation: Only one participant had AOFAS collected at 12 months and none at month 24.
0-100 point scale with 100 perfect ankle function
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
American Orthopaedic Foot and Ankle Society (AOFAS) Score.
AOFAS Month 6
|
77.8 score on a scale
Standard Deviation 16.9
|
|
American Orthopaedic Foot and Ankle Society (AOFAS) Score.
AOFAS Month 12
|
80 score on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 6, 12 and 24 month follow-upPopulation: Only one participant completed Month 12 and no participants completed this questionnaire at month 24
Description: Results are reported on a percentage scale with 100% perfect (higher is better)
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=5 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
Foot and Ankle Disability Index (FADI). ADL and Sports Scores
FADI ADL Month 6
|
75 score on a scale
Standard Deviation 16.3
|
|
Foot and Ankle Disability Index (FADI). ADL and Sports Scores
FADI Sports Month 6
|
48.1 score on a scale
Standard Deviation 29.4
|
|
Foot and Ankle Disability Index (FADI). ADL and Sports Scores
FADI ADL Month 12
|
80.8 score on a scale
Only one participant completed this questionnaire at Month 12, so a standard deviation cannot be calculated.
|
|
Foot and Ankle Disability Index (FADI). ADL and Sports Scores
FADI Sport Month 12
|
68.8 score on a scale
Only one participant completed this questionnaire at Month 12, so a standard deviation cannot be calculated.
|
SECONDARY outcome
Timeframe: calculated at 6 month follow-upFracture energy is measured in Joules. It is from CT data and measured computationally. It is a continuous measure - Higher Joules = more energy = worse fracture
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=4 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
CT-based Fracture Energy
|
20.89 Joules
Interval 12.56 to 32.6
|
SECONDARY outcome
Timeframe: 6, 12 and 24 month follow-upPopulation: Phase I participants who underwent Vertical CT ankle scans. Because of delays, final followups of the subjects were completed after funding was gone. At the time of those follow ups there had been planned budgeted CT's which would be the source material for CS measures. Because of the small number of pts it was felt the only information that was useful scientifically was for safety. Since contact stress would not contribute to that outcome a decision was made to not pay of those scans.
Vertical CT scan of ankle are segmented and analyzed using finite element analysis. Results are expressed as Contract Stress Exposure (MPa) across areas. Scans were completed in 4 participants at baseline, 4 participants at 6 month visit, 1 participant at month 12 and 1 participant at month 24. Contact stress measurements were not completed on any scans and are not avaialble.
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
CT-based Contact Stress
|
0 mPA
|
SECONDARY outcome
Timeframe: Month 0, 6, 12Population: Mean Joint Space Width
Vertical CT scan of ankle used to measure Joint Space Width at several locations to measure distance to calculate the mean tibiotalar joint space (mm).
Outcome measures
| Measure |
Phase I Single Amobarbital/Gel-One Dose
n=4 Participants
Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II.
amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention
|
|---|---|
|
CT-based Joint Space Width
Baseline
|
3.281 mm
Interval 2.658 to 3.504
|
|
CT-based Joint Space Width
Month 6
|
2.641 mm
Interval 2.271 to 2.927
|
|
CT-based Joint Space Width
Month 12
|
2.673 mm
Interval 2.673 to 2.673
|
Adverse Events
Phase I Single Amobarbital/Gel-One Dose
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place