Phase 1 Study of the Pharmacokinetics of High Dose Amoxicillin With and Without Probenecid in Pregnant Women

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05309928

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This phase I pharmacokinetic study compares four medication regimens (high or low dose amoxicillin +/- probenecid) in 40 healthy pregnant women at the time of delivery. The goal of the study is to assess medication safety and efficacy as measured by the attainment of therapeutic levels in maternal serum and amniotic fluid. This information will be used to identify a dosing regimen that is expected to reach therapeutic levels in maternal and fetal compartments. In future trials, effective dosing strategies identified can be tested in women with syphilis in pregnancy.

Condition or Disease	Intervention/Treatment	Phase
Syphilis, Congenital	Drug: Amoxicillin	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

A Rational Approach to the Identification of New Treatment Options to Prevent Congenital Syphilis: Phase 1 Study of the Pharmacokinetics of High Dose Amoxicillin With and Without Probenecid in Pregnant Women

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Amox 1 GM Amoxicillin 1000 mg PO	Drug: Amoxicillin medication administration Other Names: Probenecid
Experimental: Amox 1GM + Probenecid Amoxicillin 1000 mg PO + Probenecid 1000 mg PO	Drug: Amoxicillin medication administration Other Names: Probenecid
Experimental: Amox 3 GM Amoxicillin 3000 mg PO	Drug: Amoxicillin medication administration Other Names: Probenecid
Experimental: Amox 3 GM + Probenecid Amoxicillin 3000 mg PO + Probenecid 1000 mg PO	Drug: Amoxicillin medication administration Other Names: Probenecid

Outcome Measures

Primary Outcome Measures

Change of Amoxicillin Level in Plasma [0, 1, 2, 3, 4, 6, 8 hours after medication administration]
quantitative drug level in blood
Amoxicillin Level in Amniotic Fluid [0-8 hours after medication administration]
quantitative drug level in amniotic fluid
Amoxicillin Level in Cord Blood [at delivery]
quantitative drug level in cord blood

Secondary Outcome Measures

Incidence of Adverse Events in Women [Safety and Tolerability] [0-24 hours after administration]
safety and tolerability of medication in women
Incidence of Adverse Events in Neonates [Safety and Tolerability] [during the first 3 days of life]
safety and tolerability in neonate of in utero medication exposure

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Pregnant, engaged in prenatal care with a medical provider (at least one visit)
Estimated gestational age ≥ 35 weeks
Able to provide informed consent
English speaking

Exclusion Criteria:

Receipt of amoxicillin or probenecid within the past 7 days. (Routine GBS prophylaxis with ampicillin or other antibiotic and routine surgical prophylaxis prior to cesarean is allowed).
Known hypersensitivity or intolerance of amoxicillin, penicillin, other beta lactam or cephalosporin antibiotics or probenecid.
Spontaneous rupture of membranes prior to enrollment.
Known renal impairment (serum creatinine ≥1.0 mg/dL).
Active concomitant medications known to interact with amoxicillin: allopurinol, methotrexate, mycophenolate, immune checkpoint inhibitors (ie. pembrolizumab), tetracyclines (ie. doxycycline), vitamin K antagonists (ie. warfarin), aminoglycosides (ie. gentamicin).