Infection, BacterialPhase 1/2ADDPROPENNCT05082909

Addition of Probenecid to Penicillin-V Therapy

A Phase 1/2 study testing Probenecid in people with Infection, Bacterial, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study aims to build on previous work characterising the PK of penicillin-V to explore the potential impact of probenecid on PK-PD target attainment. Achievement of the aims of this study would provide data to support the design of experimental studies exploring the clinical impact of probenecid on treatment… Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Infection, Bacterial
What is being tested?: Probenecid
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 1 siteUnited Kingdom
Study dates: 21 Dec 2021to 7 Jul 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Adult healthy volunteers (>18 years old).
Previously taken penicillin-based antibiotics without allergic response.
Estimated Glomerular Filtration Rate (eGFR) > 90.

Who cannot join

Lacking capacity to consent.
Documented allergy to penicillin, other beta-lactam antibiotics, or probenecid.
History of G6PD Deficiency.
Known blood dyscrasias.
Anaemia (Hb < 12g/dL female, 13g/dL males).
Abnormal liver function (ALT, AST, ALP or bilirubin > ULN).

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eGFR < 90.
Pregnant or likely to become pregnant during study period.
Breastfeeding women.
Symptoms consistent with active infection.
History of gout or uric acid kidney stones.
Taking regular medication that may interact with probenecid including, but not limited to methotrexate, lorazepam, acetaminophen, oral hypoglycaemic medication, sulfa containing drugs, non-steroidal anti-inflammatory drugs.
History of evidence of any medical, neurological, or psychological condition that would expose the subject to an undue risk of a significant adverse event or interfere with study assessments during the course of the trial as determined by the clinical judgement of the investigator.
Recent involvement in other research (within prior 3 months).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Imperial Clinical Research Facility
London

Other trials in United Kingdom

About this study

Official title: Addition of Probenecid to Penicillin-V Therapy: an Open Label, Cross-over Study in Healthy Volunteers

Hypothesis: Addition of probenecid to oral phenoxymethylpenicillin (penicillin-V) has a clinically relevant effect on pharmacokinetic-pharmacodynamic (PK-PD) target attainment.

Read the detailed description

Participants will be screened and consented to attend Imperial College Clinical Research Facility (CRF) at Hammersmith Hospital on two study visits, at least 7 days apart. For one visit (randomised), participants will be required to take penicillin-V only. For their other visit, they will take penicillin-V plus probenecid at standard recommended dose. Prior to the study visits, participants may be required to have taken 36-hours of penicillin +/- probenecid, documenting this in a dosing diary. On arrival at the CRF, the participant will take an observed dose of penicillin +/- probenecid. They will undergo blood draw via needle phlebotomy or a cannula (participant choice) at 45 and 180 minutes post the observed. Samples will be spun down and frozen at -80oC. They will subsequently be analysed using an in-house HPLC-MS/MS methodology to determine total and free-unbound drug concentration.

For analysis, data from this study will be pooled with rich PK data from a prior study that assessed plasma concertation of penicillin-V in healthy volunteers. Pmetrics in R will be used to model the data looking to explore the effect of probenecid on clearance of free-penicillin-V. Probability of target attainment for streptococci species will also be estimated to evaluate the potential clinical impact of the addition of probenecid to routine penicillin-V use. Rich PK data for intravenous benzylpenicillin will be used to estimate PK-PD target attainment and PTAs for intravenous formulations, allowing direct comparison of oral and IV regimes.

Conditions: Infection, Bacterial
Being tested: Probenecid
Keywords: Penicillin, Probenecid, Pharmacokinetics
Medical subject headings: Bacterial Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ProbenecidDrug
Addition of 500mg QDS to oral penicillin.

Study groups in NCT05082909
Study group	Role	What they receive
Penicillin alone	Active comparator	Penicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours. Receives: Drug: Probenecid
Penicillin plus probenecid	Experimental	Penicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours. PLUS Probenecid 500mg QDS for 36 hours. Receives: Drug: Probenecid

What is being measured

The primary outcome is the main question the study is designed to answer.

Measurement of Total and Unbound Penicillin-V Concentration
Measurement of blood concentration at 45 minutes post dose with and without probenecid.
Measured: 45 minutes post an observed dose.
Measurement of Total and Unbound Penicillin-V Concentration
Measurement of blood concentration at 180 minutes post dose with and without probenecid.
Measured: 180 minutes post an observed dose.

Secondary outcomes (2)

Measurement of Total and Unbound Probenecid Concentration
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.
Measured: 45 minutes post an observed dose.
Measurement of Total and Unbound Probenecid Concentration
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.
Measured: 180 minutes post an observed dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Dec 20217 Jul 2022

First posted19 Oct 2021
Study start21 Dec 2021
Primary completion7 Jul 2022
Study completion7 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Infection, BacterialStudies of the same condition, open and under way.
More trials run by Imperial College LondonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Randomised, cross-over study
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05082909
Sponsor's protocol ID: 21HH6936
Acronym: ADDPROPEN
Status last verified: Jan 2025
First submitted: 17 Sep 2021
Last updated: 30 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Data will be shared upon reasonable request with appropriate permissions in place.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Infection, Bacterial trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Addition of Probenecid to Penicillin-V Therapy: an Open Label, Cross-over Study in Healthy Volunteers
ClinicalTrials.gov ID: NCT05082909
Acronym / sponsor ID: ADDPROPEN / 21HH6936
Conditions: Infection, Bacterial
Keywords: Penicillin, Probenecid, Pharmacokinetics
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Study start: 21 Dec 2021 (actual)
Primary completion: 7 Jul 2022 (actual)
Study completion: 7 Jul 2022 (actual)
First posted: 19 Oct 2021 (actual)
Results: Posted 30 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Hypothesis: Addition of probenecid to oral phenoxymethylpenicillin (penicillin-V) has a clinically relevant effect on pharmacokinetic-pharmacodynamic (PK-PD) target attainment.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2
Model description: Randomised, cross-over study

Arm	Type	Receives
Penicillin alone	Active comparator	Drug: ProbenecidPenicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours.
Penicillin plus probenecid	Experimental	Drug: ProbenecidPenicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours. PLUS Probenecid 500mg QDS for 36 hours.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Adult healthy volunteers (>18 years old).
Previously taken penicillin-based antibiotics without allergic response.
Estimated Glomerular Filtration Rate (eGFR) > 90.

Key exclusion criteria (14 listed)

Lacking capacity to consent.
Documented allergy to penicillin, other beta-lactam antibiotics, or probenecid.
History of G6PD Deficiency.
Known blood dyscrasias.
Anaemia (Hb < 12g/dL female, 13g/dL males).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ProbenecidAddition of 500mg QDS to oral penicillin.	Drug	Penicillin alone, Penicillin plus probenecid

Primary outcome

Measurement of Total and Unbound Penicillin-V Concentration
Time frame: 45 minutes post an observed dose.
Measurement of blood concentration at 45 minutes post dose with and without probenecid.
Measurement of Total and Unbound Penicillin-V Concentration
Time frame: 180 minutes post an observed dose.
Measurement of blood concentration at 180 minutes post dose with and without probenecid.

2 secondary outcomes

Measurement of Total and Unbound Probenecid Concentration
Time frame: 45 minutes post an observed dose.
Measurement of Total and Unbound Probenecid Concentration
Time frame: 180 minutes post an observed dose.

Results and safety

Results posted to the registry on 30 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Penicillin 250mg QDS THEN Penicillin 250mg QDS Plus Probenecid 500mg QDS	3	3
Penicillin 500mg QDS THEN Penicillin 500mg QDS Plus Probenecid 500mg QDS	4	4
Penicillin 750mg QDS THEN Penicillin 750mg QDS Plus Probenecid 500mg QDS	4	3
Penicillin 250mg QDS Plus Probenecid 500mg QDS THEN Penicillin 250mg QDS.	2	2
Penicillin 500mg QDS Plus Probenecid 500mg QDS THEN Penicillin 500mg QDS.	6	6
Penicillin 750mg QDS Plus Probenecid 500mg QDS THEN Penicillin 750mg QDS.	2	2

Primary outcome: Measurement of Total and Unbound Penicillin-V Concentration

Time frame: 45 minutes post an observed dose.. Mean (Standard Deviation). Unit: mg/L

Measure	250mg Penicillin Arm 1 n = 3	250mg Penicillin Arm 2 n = 2	500mg Penicillin Arm 1 n = 4	500mg Penicillin Arm 2 n = 6	750mg Penicillin Arm 1 n = 3	750mg Penicillin Arm 2 n = 2
Total penicillin concentration (mg/L) - penicillin alone	2.07 (0.16)	2.8 (0.10)	5.03 (1.46)	3.62 (1.56)	6.53 (5.38)	6.2 (0.8)
Unbound penicillin concentration (mg/L) - penicillin alone	0.39 (0.04)	0.56 (0.01)	0.97 (0.22)	0.65 (0.27)	1.22 (0.34)	1.08 (0.15)
Total penicillin concentration (mg/L) - penicillin plus probenecid	4.83 (0.91)	7.45 (1.05)	10.88 (2.41)	6.50 (3.20)	12 (2.27)	12 (3)
Unbound penicillin concentration (mg/L) - penicillin plus probenecid	1.58 (0.87)	1.74 (0.14)	2.36 (0.59)	1.52 (0.76)	2.63 (0.64)	2.84 (0.77)

Primary outcome: Measurement of Total and Unbound Penicillin-V Concentration

Time frame: 180 minutes post an observed dose.. Mean (Standard Deviation). Unit: mg/L

Measure	250mg Penicillin Arm 1 n = 3	250mg Penicillin Arm 2 n = 2	500mg Penicillin Arm 1 n = 4	500mg Penicillin Arm 2 n = 6	750mg Penicillin Arm 1 n = 3	750mg Penicillin Arm 2 n = 2
Total penicillin concentration (mg/L) - penicillin alone	0.13 (0.05)	0.85 (0.45)	0.98 (0.76)	0.85 (0.26)	1.97 (0.76)	0.45 (0.15)
Unbound penicillin concentration (mg/L) - penicillin alone	0.03 (0.01)	0.15 (0.07)	0.18 (0.14)	0.16 (0.05)	0.35 (0.13)	0.09 (0.03)
Total penicillin concentration (mg/L) - penicillin plus probenecid	1.58 (0.87)	2.35 (1.15)	5.18 (2.15)	2.22 (0.56)	6.67 (3.09)	3.55 (1.45)
Unbound penicillin concentration (mg/L) - penicillin plus probenecid	0.33 (0.16)	0.49 (0.21)	1.18 (0.51)	0.49 (0.11)	1.46 (0.78)	0.81 (0.34)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Data collected over 3 weeks from participant enrolment to final visit completion per participant.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Penicillin Alone	0 of 20 (0%)	7 of 20 (35%)	0 of 20
Penicillin Plus Probenecid	0 of 20 (0%)	8 of 20 (40%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Data will be shared upon reasonable request with appropriate permissions in place.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Timothy Rawson, PhD principal investigator

Imperial College London

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Probenecid in people with Infection, Bacterial, run by Imperial College London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of Total and Unbound Penicillin-V Concentration (time frame: 45 minutes post an observed dose.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05082909.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.