Addition of Probenecid to Penicillin-V Therapy

NCT05082909 | Completed Phase 1 Results DMC

• 1 other identifier: 21HH6936
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Infection, Bacterial

Keywords

Penicillin; Probenecid; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Measurement of Total and Unbound Penicillin-V Concentration

  Measurement of blood concentration at 45 minutes post dose with and without probenecid.

  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.

  180 minutes post an observed dose.

Secondary Outcomes (2)

• Measurement of Total and Unbound Probenecid Concentration

  45 minutes post an observed dose.

• Measurement of Total and Unbound Probenecid Concentration

  180 minutes post an observed dose.

Study Arms (2)

Penicillin alone

ACTIVE COMPARATOR

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

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.

Drug: Probenecid

Interventions

Probenecid DRUG

Addition of 500mg QDS to oral penicillin.

Penicillin alone; Penicillin plus probenecid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial Clinical Research Facility

London, United Kingdom

Location

MeSH Terms

Conditions

Bacterial Infections

Interventions

Probenecid

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Dr Timothy Rawson
• Organization: Imperial College London

antibiotic.research@imperial.ac.uk

07891750151

Study Officials

• Timothy Rawson, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, cross-over study

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: October 19, 2021
• Study Start: December 21, 2021
• Primary Completion: July 7, 2022
• Study Completion: July 7, 2022
• Last Updated: January 30, 2025
• Results First Posted: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The protocol will be available from commencement of study. The clinical study report will be published within 12 months of completion of the study.
• Access Criteria: Access via the study principle investigator or online publications.

Locations

GB (1)