Trial Outcomes & Findings for Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study (NCT NCT01944371)
NCT ID: NCT01944371
Last Updated: 2020-05-05
Results Overview
Fold change cell-associated HIV RNA in Total CD4 T-Cells.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Baseline and 3 days
Results posted on
2020-05-05
Participant Flow
Of 34 participants screened for eligibility, we recruited 30 participants at The Alfred Hospital (Melbourne, VIC, Australia) and the San Francisco General Hospital (San Francisco, CA, USA) between September 24, 2013, and March 31, 2014.
Participant milestones
| Measure |
Disulfiram 500mg
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
Baseline characteristics by cohort
| Measure |
Disulfiram 500mg
n=10 Participants
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
n=10 Participants
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
n=10 Participants
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53 years
n=93 Participants
|
54 years
n=4 Participants
|
51 years
n=27 Participants
|
53 years
n=483 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
28 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
22 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=93 Participants
|
6 participants
n=4 Participants
|
5 participants
n=27 Participants
|
15 participants
n=483 Participants
|
|
Region of Enrollment
Australia
|
6 participants
n=93 Participants
|
4 participants
n=4 Participants
|
5 participants
n=27 Participants
|
15 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline and 3 daysFold change cell-associated HIV RNA in Total CD4 T-Cells.
Outcome measures
| Measure |
Disulfiram 500mg
n=10 Participants
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
n=10 Participants
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
n=10 Participants
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
|---|---|---|---|
|
Cell-associated HIV RNA
|
1.7 Fold change
Interval 1.3 to 2.2
|
1.9 Fold change
Interval 1.6 to 2.4
|
1.6 Fold change
Interval 1.2 to 2.1
|
SECONDARY outcome
Timeframe: Baseline and 3 daysFold change in plasma HIV RNA levels from baseline through day 3
Outcome measures
| Measure |
Disulfiram 500mg
n=10 Participants
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
n=10 Participants
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
n=10 Participants
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
|---|---|---|---|
|
Plasma HIV RNA
|
1.50 Fold change
Interval 0.36 to 3.4
|
0.90 Fold change
Interval 0.18 to 1.7
|
1.22 Fold change
Interval 0.32 to 2.83
|
SECONDARY outcome
Timeframe: Baseline and 30 daysFold change in HIV DNA levels between Baseline and Day 30
Outcome measures
| Measure |
Disulfiram 500mg
n=10 Participants
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
n=10 Participants
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
n=10 Participants
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
|---|---|---|---|
|
Proviral HIV DNA
|
1.07 Fold change
Interval 0.89 to 1.28
|
0.83 Fold change
Interval 0.6 to 1.15
|
0.91 Fold change
Interval 0.77 to 1.05
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 31 daysPlasma concentrations of disulfiram were measured on dosing day 1 (hours 0, 2, and 6), day 2 (hour 0), and day 3 (hours 0, 2, and 6), as well as on postdosing days 4, 8, and 31. The area under the curve (AUC) levels over 72 hours was estimated.
Outcome measures
| Measure |
Disulfiram 500mg
n=10 Participants
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
n=10 Participants
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
n=10 Participants
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
|---|---|---|---|
|
Disufiram Pharmacokinetics
|
3,186 mg-hour/liter
|
8,386 mg-hour/liter
|
22,331 mg-hour/liter
|
Adverse Events
Disulfiram 500mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Disulfiram 1000mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Disulfiram 2000mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Disulfiram 500mg
n=10 participants at risk
500mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 1000mg
n=10 participants at risk
1000mg disulfiram by mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
Disulfiram 2000mg
n=10 participants at risk
2000mg disulfiram per mouth per day for 3 days
Disulfiram: This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
|
|---|---|---|---|
|
Hepatobiliary disorders
Increased aspartate aminotransferase
|
10.0%
1/10 • Number of events 1 • Subjects were monitored in an outpatient clinic during the first 6 hours post-dose on days 1 and 3. At each visit, subjects were assessed for any new symptoms and vital signs. A complete blood count and complete metabolic panel were performed during screening, and then at Days 1, 2, 3, 4, 8 and 31. No evaluations were made after Day 31.
The grading system for drug toxicities is located in the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification, August 2009), which can be found on the DAIDS RSC Web Site (http://rsc.tech-res.com/safetyandpharmacovigilance/.)
|
10.0%
1/10 • Number of events 1 • Subjects were monitored in an outpatient clinic during the first 6 hours post-dose on days 1 and 3. At each visit, subjects were assessed for any new symptoms and vital signs. A complete blood count and complete metabolic panel were performed during screening, and then at Days 1, 2, 3, 4, 8 and 31. No evaluations were made after Day 31.
The grading system for drug toxicities is located in the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification, August 2009), which can be found on the DAIDS RSC Web Site (http://rsc.tech-res.com/safetyandpharmacovigilance/.)
|
0.00%
0/10 • Subjects were monitored in an outpatient clinic during the first 6 hours post-dose on days 1 and 3. At each visit, subjects were assessed for any new symptoms and vital signs. A complete blood count and complete metabolic panel were performed during screening, and then at Days 1, 2, 3, 4, 8 and 31. No evaluations were made after Day 31.
The grading system for drug toxicities is located in the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification, August 2009), which can be found on the DAIDS RSC Web Site (http://rsc.tech-res.com/safetyandpharmacovigilance/.)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place