Addition of Probenecid to Penicillin-V Therapy

NCT ID: NCT05082909

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-21
• Study Completion Date: 2022-07-07

Brief 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 outcomes and also provide a rationale for exploration of probenecid's effects on a larger number of beta-lactam antibiotics.

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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Penicillin alone

Penicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours.

Group Type: ACTIVE_COMPARATOR

Probenecid

Intervention Type: DRUG

Addition of 500mg QDS to oral penicillin.

Penicillin plus probenecid

Penicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours.

PLUS

Probenecid 500mg QDS for 36 hours.

Group Type: EXPERIMENTAL

Probenecid

Intervention Type: DRUG

Addition of 500mg QDS to oral penicillin.

Interventions

Probenecid

Addition of 500mg QDS to oral penicillin.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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).
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy Rawson, PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial Clinical Research Facility

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

21HH6936

Identifier Type: -

Identifier Source: org_study_id