Trial Outcomes & Findings for Addition of Probenecid to Penicillin-V Therapy (NCT NCT05082909)
NCT ID: NCT05082909
Last Updated: 2025-01-30
Results Overview
Measurement of blood concentration at 45 minutes post dose with and without probenecid.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
21 participants
Primary outcome timeframe
45 minutes post an observed dose.
Results posted on
2025-01-30
Participant Flow
Participant milestones
| Measure |
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
Sequence:
1. Penicillin orally at dose of 250mg for 36 hours.
2. Washout period
3. Penicillin orally at dose of 250mg PLUS probenecid 500mg QDS for 36 hours.
|
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
Sequence:
1. Penicillin orally at dose of 500mg for 36 hours.
2. Washout period
3. Penicillin orally at dose of 500mg PLUS probenecid 500mg QDS for 36 hours.
|
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
Sequence:
1. Penicillin orally at dose of 750mg for 36 hours.
2. Washout period
3. Penicillin orally at dose of 750mg PLUS probenecid 500mg QDS for 36 hours.
|
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS.
Sequence:
1. Penicillin orally at dose of 250mg PLUS probenecid 500mg QDS for 36 hours.
2. Washout period.
3. Penicillin orally at dose of 250mg for 36 hours.
|
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS.
Sequence:
1. Penicillin orally at dose of 500mg PLUS probenecid 500mg QDS for 36 hours.
2. Washout period.
3. Penicillin orally at dose of 500mg for 36 hours.
|
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS.
Sequence:
1. Penicillin orally at dose of 750mg PLUS probenecid 500mg QDS for 36 hours.
2. Washout period.
3. Penicillin orally at dose of 750mg for 36 hours.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
4
|
2
|
6
|
2
|
|
Overall Study
COMPLETED
|
3
|
4
|
3
|
2
|
6
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
Sequence:
1. Penicillin orally at dose of 250mg for 36 hours.
2. Washout period
3. Penicillin orally at dose of 250mg PLUS probenecid 500mg QDS for 36 hours.
|
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
Sequence:
1. Penicillin orally at dose of 500mg for 36 hours.
2. Washout period
3. Penicillin orally at dose of 500mg PLUS probenecid 500mg QDS for 36 hours.
|
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
Sequence:
1. Penicillin orally at dose of 750mg for 36 hours.
2. Washout period
3. Penicillin orally at dose of 750mg PLUS probenecid 500mg QDS for 36 hours.
|
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS.
Sequence:
1. Penicillin orally at dose of 250mg PLUS probenecid 500mg QDS for 36 hours.
2. Washout period.
3. Penicillin orally at dose of 250mg for 36 hours.
|
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS.
Sequence:
1. Penicillin orally at dose of 500mg PLUS probenecid 500mg QDS for 36 hours.
2. Washout period.
3. Penicillin orally at dose of 500mg for 36 hours.
|
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS.
Sequence:
1. Penicillin orally at dose of 750mg PLUS probenecid 500mg QDS for 36 hours.
2. Washout period.
3. Penicillin orally at dose of 750mg for 36 hours.
|
|---|---|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
n=3 Participants
Sequence:
1. Penicillin orally at dose of 250mg QDS for 36 hours.
2. Washout period
3. Penicillin orally at dose of 250mg QDS and probenecid 500mg QDS to oral penicillin for 36 hours.
|
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
n=4 Participants
Sequence:
1. Penicillin orally at dose of 500mg QDS for 36 hours.
2. Washout period
3. Penicillin orally at dose of 500mg QDS and probenecid 500mg QDS to oral penicillin for 36 hours.
|
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
n=4 Participants
Sequence:
1. Penicillin orally at dose of 750mg QDS for 36 hours.
2. Washout period
3. Penicillin orally at dose of 750mg QDS and probenecid 500mg QDS to oral penicillin for 36 hours
|
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS
n=2 Participants
Sequence:
1. Penicillin orally at dose of 250mg QDS and probenecid 500mg QDS to oral penicillin for 36 hours
2. Washout period
3. Penicillin orally at dose of 250mg QDS for 36 hours.
|
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS
n=6 Participants
Sequence:
1. Penicillin orally at dose of 500mg QDS and probenecid 500mg QDS to oral penicillin for 36 hours
2. Washout period
3. Penicillin orally at dose of 500mg QDS for 36 hours.
|
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS
n=2 Participants
Sequence:
1. Penicillin orally at dose of 750mg QDS and probenecid 500mg QDS to oral penicillin for 36 hours
2. Washout period
3. Penicillin orally at dose of 750mg QDS for 36 hours.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
50 years
STANDARD_DEVIATION 18 • n=3 Participants
|
55 years
STANDARD_DEVIATION 11 • n=4 Participants
|
52 years
STANDARD_DEVIATION 14 • n=4 Participants
|
48 years
STANDARD_DEVIATION 22 • n=2 Participants
|
67 years
STANDARD_DEVIATION 6 • n=6 Participants
|
30 years
STANDARD_DEVIATION 2 • n=2 Participants
|
53 years
STANDARD_DEVIATION 17 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=3 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=2 Participants
|
4 Participants
n=6 Participants
|
0 Participants
n=2 Participants
|
8 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=3 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=2 Participants
|
2 Participants
n=6 Participants
|
2 Participants
n=2 Participants
|
13 Participants
n=21 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United Kingdom
|
3 participants
n=3 Participants
|
4 participants
n=4 Participants
|
4 participants
n=4 Participants
|
2 participants
n=2 Participants
|
6 participants
n=6 Participants
|
2 participants
n=2 Participants
|
21 participants
n=21 Participants
|
|
Weight
|
68 Kilograms
STANDARD_DEVIATION 5 • n=3 Participants
|
68 Kilograms
STANDARD_DEVIATION 8 • n=4 Participants
|
74 Kilograms
STANDARD_DEVIATION 11 • n=4 Participants
|
70 Kilograms
STANDARD_DEVIATION 0 • n=2 Participants
|
71 Kilograms
STANDARD_DEVIATION 6 • n=6 Participants
|
88 Kilograms
STANDARD_DEVIATION 1 • n=2 Participants
|
72 Kilograms
STANDARD_DEVIATION 9 • n=21 Participants
|
|
Height
|
167 cm
STANDARD_DEVIATION 10 • n=3 Participants
|
169 cm
STANDARD_DEVIATION 10 • n=4 Participants
|
170 cm
STANDARD_DEVIATION 5 • n=4 Participants
|
171 cm
STANDARD_DEVIATION 5 • n=2 Participants
|
174 cm
STANDARD_DEVIATION 4 • n=6 Participants
|
179 cm
STANDARD_DEVIATION 3 • n=2 Participants
|
171.5 cm
STANDARD_DEVIATION 7.8 • n=21 Participants
|
|
Creatinine
|
62 micromol/L
STANDARD_DEVIATION 5 • n=3 Participants
|
68 micromol/L
STANDARD_DEVIATION 6 • n=4 Participants
|
69 micromol/L
STANDARD_DEVIATION 2 • n=4 Participants
|
64 micromol/L
STANDARD_DEVIATION 3 • n=2 Participants
|
70 micromol/L
STANDARD_DEVIATION 7 • n=6 Participants
|
78 micromol/L
STANDARD_DEVIATION 5 • n=2 Participants
|
68 micromol/L
STANDARD_DEVIATION 9 • n=21 Participants
|
|
Albumin
|
42 g/L
STANDARD_DEVIATION 3 • n=3 Participants
|
41 g/L
STANDARD_DEVIATION 2 • n=4 Participants
|
41 g/L
STANDARD_DEVIATION 2 • n=4 Participants
|
41 g/L
STANDARD_DEVIATION 3 • n=2 Participants
|
40 g/L
STANDARD_DEVIATION 2 • n=6 Participants
|
43 g/L
STANDARD_DEVIATION 1 • n=2 Participants
|
41 g/L
STANDARD_DEVIATION 2 • n=21 Participants
|
PRIMARY outcome
Timeframe: 45 minutes post an observed dose.Measurement of blood concentration at 45 minutes post dose with and without probenecid.
Outcome measures
| Measure |
250mg Penicillin Arm 1
n=3 Participants
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
|
250mg Penicillin Arm 2
n=2 Participants
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS
|
500mg Penicillin Arm 1
n=4 Participants
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
|
500mg Penicillin Arm 2
n=6 Participants
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS
|
750mg Penicillin Arm 1
n=3 Participants
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
|
750mg Penicillin Arm 2
n=2 Participants
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS
|
|---|---|---|---|---|---|---|
|
Measurement of Total and Unbound Penicillin-V Concentration
Unbound penicillin concentration (mg/L) - penicillin plus probenecid
|
1.58 mg/L
Standard Deviation 0.87
|
1.74 mg/L
Standard Deviation 0.14
|
2.36 mg/L
Standard Deviation 0.59
|
1.52 mg/L
Standard Deviation 0.76
|
2.63 mg/L
Standard Deviation 0.64
|
2.84 mg/L
Standard Deviation 0.77
|
|
Measurement of Total and Unbound Penicillin-V Concentration
Total penicillin concentration (mg/L) - penicillin alone
|
2.07 mg/L
Standard Deviation 0.16
|
2.8 mg/L
Standard Deviation 0.10
|
5.03 mg/L
Standard Deviation 1.46
|
3.62 mg/L
Standard Deviation 1.56
|
6.53 mg/L
Standard Deviation 5.38
|
6.2 mg/L
Standard Deviation 0.8
|
|
Measurement of Total and Unbound Penicillin-V Concentration
Unbound penicillin concentration (mg/L) - penicillin alone
|
0.39 mg/L
Standard Deviation 0.04
|
0.56 mg/L
Standard Deviation 0.01
|
0.97 mg/L
Standard Deviation 0.22
|
0.65 mg/L
Standard Deviation 0.27
|
1.22 mg/L
Standard Deviation 0.34
|
1.08 mg/L
Standard Deviation 0.15
|
|
Measurement of Total and Unbound Penicillin-V Concentration
Total penicillin concentration (mg/L) - penicillin plus probenecid
|
4.83 mg/L
Standard Deviation 0.91
|
7.45 mg/L
Standard Deviation 1.05
|
10.88 mg/L
Standard Deviation 2.41
|
6.50 mg/L
Standard Deviation 3.20
|
12 mg/L
Standard Deviation 2.27
|
12 mg/L
Standard Deviation 3
|
PRIMARY outcome
Timeframe: 180 minutes post an observed dose.Measurement of blood concentration at 180 minutes post dose with and without probenecid.
Outcome measures
| Measure |
250mg Penicillin Arm 1
n=3 Participants
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
|
250mg Penicillin Arm 2
n=2 Participants
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS
|
500mg Penicillin Arm 1
n=4 Participants
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
|
500mg Penicillin Arm 2
n=6 Participants
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS
|
750mg Penicillin Arm 1
n=3 Participants
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
|
750mg Penicillin Arm 2
n=2 Participants
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS
|
|---|---|---|---|---|---|---|
|
Measurement of Total and Unbound Penicillin-V Concentration
Total penicillin concentration (mg/L) - penicillin alone
|
0.13 mg/L
Standard Deviation 0.05
|
0.85 mg/L
Standard Deviation 0.45
|
0.98 mg/L
Standard Deviation 0.76
|
0.85 mg/L
Standard Deviation 0.26
|
1.97 mg/L
Standard Deviation 0.76
|
0.45 mg/L
Standard Deviation 0.15
|
|
Measurement of Total and Unbound Penicillin-V Concentration
Unbound penicillin concentration (mg/L) - penicillin alone
|
0.03 mg/L
Standard Deviation 0.01
|
0.15 mg/L
Standard Deviation 0.07
|
0.18 mg/L
Standard Deviation 0.14
|
0.16 mg/L
Standard Deviation 0.05
|
0.35 mg/L
Standard Deviation 0.13
|
0.09 mg/L
Standard Deviation 0.03
|
|
Measurement of Total and Unbound Penicillin-V Concentration
Total penicillin concentration (mg/L) - penicillin plus probenecid
|
1.58 mg/L
Standard Deviation 0.87
|
2.35 mg/L
Standard Deviation 1.15
|
5.18 mg/L
Standard Deviation 2.15
|
2.22 mg/L
Standard Deviation 0.56
|
6.67 mg/L
Standard Deviation 3.09
|
3.55 mg/L
Standard Deviation 1.45
|
|
Measurement of Total and Unbound Penicillin-V Concentration
Unbound penicillin concentration (mg/L) - penicillin plus probenecid
|
0.33 mg/L
Standard Deviation 0.16
|
0.49 mg/L
Standard Deviation 0.21
|
1.18 mg/L
Standard Deviation 0.51
|
0.49 mg/L
Standard Deviation 0.11
|
1.46 mg/L
Standard Deviation 0.78
|
0.81 mg/L
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: 45 minutes post an observed dose.Population: All 20 participants received the same dose (500mg QDS) of probenecid regardless of study arm. Results are therefore presented for all participants for this outcome.
Measurement of blood concentration at 45 minutes post observed probenecid dose. Combined data for all participants given that the same dose of probenecid was taken by all participants.
Outcome measures
| Measure |
250mg Penicillin Arm 1
n=20 Participants
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
|
250mg Penicillin Arm 2
n=20 Participants
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS
|
500mg Penicillin Arm 1
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
|
500mg Penicillin Arm 2
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS
|
750mg Penicillin Arm 1
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
|
750mg Penicillin Arm 2
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS
|
|---|---|---|---|---|---|---|
|
Measurement of Total and Unbound Probenecid Concentration
|
79.0 mg/L
Standard Deviation 21.4
|
6.6 mg/L
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 180 minutes post an observed dose.Population: All 20 participants received the same dose (500mg QDS) of probenecid regardless of study arm. Results are therefore presented for all participants for this outcome.
Measurement of blood concentration at 180 minutes post observed probenecid dose. Combined data for all participants given that the same dose of probenecid was taken by all participants.
Outcome measures
| Measure |
250mg Penicillin Arm 1
n=20 Participants
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS
|
250mg Penicillin Arm 2
n=20 Participants
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS
|
500mg Penicillin Arm 1
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS
|
500mg Penicillin Arm 2
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS
|
750mg Penicillin Arm 1
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS
|
750mg Penicillin Arm 2
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS
|
|---|---|---|---|---|---|---|
|
Measurement of Total and Unbound Probenecid Concentration
|
81.1 mg/L
Standard Deviation 20.6
|
6.6 mg/L
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
Adverse Events
Penicillin Alone
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Penicillin Plus Probenecid
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Penicillin Alone
n=20 participants at risk
Penicillin orally QDS for 36 hours.
This data has been grouped to present a comparison of penicillin vs. probenecid irrespective of dose.
|
Penicillin Plus Probenecid
n=20 participants at risk
Penicillin orally for 36 hours.
PLUS
Probenecid 500mg QDS for 36 hours.
This data has been grouped to present a comparison of penicillin vs. probenecid irrespective of dose.
|
|---|---|---|
|
Gastrointestinal disorders
Mild, expected (GI side effects)
|
15.0%
3/20 • Number of events 4 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
25.0%
5/20 • Number of events 7 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
|
Nervous system disorders
Mild, expected (headache)
|
5.0%
1/20 • Number of events 1 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
15.0%
3/20 • Number of events 3 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
|
Infections and infestations
Unexpected, not related to IMP
|
5.0%
1/20 • Number of events 1 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
0.00%
0/20 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
|
Musculoskeletal and connective tissue disorders
Unexpected, not related to IMP
|
5.0%
1/20 • Number of events 1 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
0.00%
0/20 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
|
Metabolism and nutrition disorders
Unexpected, possible association with IMP
|
5.0%
1/20 • Number of events 1 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
0.00%
0/20 • Data collected over 3 weeks from participant enrolment to final visit completion per participant.
Results have been reported as per our protocol. Results are not reported per arm/group as dose dependent adverse events were not assessed. Assessment of adverse events aimed to compare penicillin alone against penicillin with probenecid, as is presented in this table.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place