Neonatal InfectionPhase 1NCT04916951
Oral Amoxicillin and Cephalexin PK/PD in Neonates
A Phase 1 study testing Amoxicillin and Cephalexin in people with Neonatal Infection, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The goal of this study is to figure out the best doses for two oral antibiotics (called amoxicillin and cephalexin) when they are used to treat infections in newborns and young infants. In order to do this, the study plans to enroll two groups of young infants who are admitted to the Children's Hospital Colorado. Read more about this study
- Who is it for?
- Ages 1 day to 60 days
- Conditions the study is for
- Neonatal Infection
- What is being tested?
- Amoxicillin and Cephalexin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2021to 30 Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 1 day to 60 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients admitted to Children's Hospital Colorado derived from two groups:
- Group 1-patients specifically receiving enteral amoxicillin (with or without clavulanate) or cephalexin for any clinical indication;
- Group 2-patients receiving any IV antibiotic who are tolerating full enteral feeds and/or enteral medications.
Who cannot join
- Across both groups, exclusion criteria are: (1) weight <2kg, (2) renal dysfunction, including the use of any renal replacement therapy, (3) significant β-lactam allergy, (4) GI disorders significantly impairing drug absorption, (5) use of external circuits that would affect the study drug's volume of distribution (e.g. ECMO), and (6) clinically significant anemia precluding study-related blood draws.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
Official title: Oral Amoxicillin and Cephalexin Pharmacokinetics/Pharmacodynamics (PK/PD) in the Neonatal Intensive Care Unit
The goal of this study is to figure out the best doses for two oral antibiotics (called amoxicillin and cephalexin) when they are used to treat infections in newborns and young infants. In order to do this, the study plans to enroll two groups of young infants who are admitted to the Children's Hospital Colorado. In the first group, infants already receiving one of these two antibiotics will be enrolled. Over a few days in the hospital, up to 5 blood samples will be collected from each infant to measure how much of the drug is in their body at different points in time after a dose. In the second group, infants who are already receiving an IV antibiotic and who are eating normally or receiving oral medications will be enrolled. These infants will receive one dose by mouth of either amoxicillin or cephalexin, in addition to the IV antibiotic already being used to treat their infection. After the oral antibiotic dose,blood will be drawn every few hours to measure how much of the drug is still in their body. Blood levels of the antibiotics will be used to calculate how much and how often both antibiotics would need to be given to treat a variety of infections that are common in infants. The study will calculate if using a single blood level can predict whether or not an infant might be at risk of the antibiotic not working well enough for them.
Read the detailed description
This proposal's objective is to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) of enteral amoxicillin and cephalexin in neonates and young infants admitted to the hospital, characterize age-stratified PK/PD parameters, and use these data to improve neonatal antibiotic dosing strategies. This will involve developing and validating small-volume sampling assays using dried blood spots. The study hypothesizes that there will be significant inter-individual variation in amoxicillin and cephalexin PK/PD parameters in neonates and that delayed absorption and elimination will lead to longer times to maximal concentrations (Tmax) and prolonged half-lives (T1/2), most prominently in younger ages. In addition, the study hypothesizes that high inter-individual variability will lead to unacceptably low attainment of PK/PD efficacy targets using standard dosing regimens. To address this low target attainment, the study will aim to incorporate therapeutic drug monitoring (TDM), using a serum trough concentration, into this PD model to create a method that more accurately identifies patients likely to succeed with oral (PO) dosing. Preliminary physiologically based pharmacokinetic (PBPK) modeling and intestinal transporter genotyping will also provide a foundation for future studies on the most important factors that lead to interpatient variability in PK parameters. The neonatal population has much to gain from an improved understanding of age-specific PK/PD, as well as more frequent, and earlier, intravenous (IV) to PO transition of antibiotics. The specific aims of this study are to:
Specific Aim 1: Use a population PK approach to define PK parameters of enteral amoxicillin and cephalexin in infants aged 0-60 days, stratified by age group. This will include building preliminary physiologically based pharmacokinetic (PBPK) models for each drug.
Specific Aim 2: Develop and validate amoxicillin and cephalexin dried-blood spot assays.
Specific Aim 3: Perform PD modeling 3A: Perform PD modeling (including Monte Carlo simulation) to evaluate the expected PK/PD target attainment of amoxicillin and cephalexin by age group.
3B: Identify a minimum trough threshold needed to establish 95% target attainment.
Exploratory Aim: Correlate patient genotype for H(+)/peptide transporters (PEPT) 1 and 2 and the organic-anion-transporting polypeptide (OATP) family of transporters with patient-specific PK parameters.
- Conditions
- Neonatal Infection
- Being tested
- Amoxicillin, Cephalexin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmoxicillinDrug
oral one-time dose of amoxicillin
CephalexinDrug
oral one-time dose of cephalexin
| Study group | Role | What they receive |
|---|---|---|
| Amoxicillin - standard-of-care dose | No intervention | Obtain amoxicillin plasma concentrations in patients already receiving amoxicillin |
| Cephalexin - standard-of-care dose | No intervention | Obtain cephalexin plasma concentrations in patients already receiving cephalexin |
| Amoxicillin - study dose | Experimental | Obtain amoxicillin plasma concentrations after a study-administered dose of amoxicillin Receives: Drug: Amoxicillin |
| Cephalexin - study dose | Experimental | Obtain cephalexin plasma concentrations after a study-administered dose of cephalexin Receives: Drug: Cephalexin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time above Minimum Inhibitory Concentration (T > MIC)
As a surrogate of treatment efficacy for amoxicillin and cephalexin, the investigators will determine the time that free plasma concentrations (fT > MIC) of amoxicillin and cephalexin remain above the minimum inhibitory concentration (MIC) of common neonatal pathogens. Monte Carlo simulation will be used to assess for the likelihood of fT > MIC dosing goals.
Measured: up to 24 hours
Secondary outcomes (7)
Clearance (CL/F) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the Clearance, or CL/F (L/h/kg), of both drugs.
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Volume of Distribution (V/F) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the Volume of Distribution, or V/F (L/kg), of both drugs
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Half life (T1/2) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the half life, or T1/2 (hours), of both drugs.
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Area under the curve (AUC) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the area under the curve, or AUC (h*mg/L), of both drugs.
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Peak serum drug concentration (Cmax) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the peak serum drug concentration, or Cmax (mg/L), of both drugs.
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Minimum serum drug concentration (Cmin) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the minimum serum drug concentration, or Cmin (mg/L), of both drugs.
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Time at which maximal drug concentration is achieved (Tmax) of amoxicillin and cephalexin
In defining pharmacokinetic parameters for both amoxicillin and cephalexin, the investigators will assess the time at which maximal drug concentration is achieved, or Tmax (hours), of both drugs.
Measured: Plasma drug concentrations obtained within 12 hours of a dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2021
- Study start14 Jul 2021
- Primary completion30 Nov 2025
- Study completion30 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal InfectionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Haynes, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04916951
- Sponsor's protocol ID
- 20-2877
- Status last verified
- May 2026
- First submitted
- 1 Jun 2021
- Last updated
- 19 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Amoxicillin and Cephalexin Pharmacokinetics/Pharmacodynamics (PK/PD) in the Neonatal Intensive Care Unit
- ClinicalTrials.gov ID
- NCT04916951
- Acronym / sponsor ID
- 20-2877
- Conditions
- Neonatal Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 14 Jul 2021 (actual)
- Primary completion
- 30 Nov 2025 (actual)
- Study completion
- 30 Nov 2025 (actual)
- First posted
- 8 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to figure out the best doses for two oral antibiotics (called amoxicillin and cephalexin) when they are used to treat infections in newborns and young infants. In order to do this, the study plans to enroll two groups of young infants who are admitted to the Children's Hospital Colorado. In the first group, infants already receiving one of these two antibiotics will be enrolled. Over a few days in the hospital, up to 5 blood samples will be collected from each infant to measure how much of the drug is in their body at different points in time after a dose. In the second group, infants who are already receiving an IV antibiotic and who are eating normally or receiving oral medications will be enrolled. These infants will receive one dose by mouth of either amoxicillin or cephalexin, in addition to the IV antibiotic already being used to treat their infection. After the oral antibiotic dose,blood will be drawn every few hours to measure how much of the drug is still in their body. Blood levels of the antibiotics will be used to calculate how much and how often both antibiotics would need to be given to treat a variety of infections that are common in infants. The study will calculate if using a single blood level can predict whether or not an infant might be at risk of the antibiotic not working well enough for them.
Detailed description
This proposal's objective is to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) of enteral amoxicillin and cephalexin in neonates and young infants admitted to the hospital, characterize age-stratified PK/PD parameters, and use these data to improve neonatal antibiotic dosing strategies. This will involve developing and validating small-volume sampling assays using dried blood spots. The study hypothesizes that there will be significant inter-individual variation in amoxicillin and cephalexin PK/PD parameters in neonates and that delayed absorption and elimination will lead to longer times to maximal concentrations (Tmax) and prolonged half-lives (T1/2), most prominently in younger ages. In addition, the study hypothesizes that high inter-individual variability will lead to unacceptably low attainment of PK/PD efficacy targets using standard dosing regimens. To address this low target attainment, the study will aim to incorporate therapeutic drug monitoring (TDM), using a serum trough concentration, into this PD model to create a method that more accurately identifies patients likely to succeed with oral (PO) dosing. Preliminary physiologically based pharmacokinetic (PBPK) modeling and intestinal transporter genotyping will also provide a foundation for future studies on the most important factors that lead to interpatient variability in PK parameters. The neonatal population has much to gain from an improved understanding of age-specific PK/PD, as well as more frequent, and earlier, intravenous (IV) to PO transition of antibiotics. The specific aims of this study are to:
Specific Aim 1: Use a population PK approach to define PK parameters of enteral amoxicillin and cephalexin in infants aged 0-60 days, stratified by age group. This will include building preliminary physiologically based pharmacokinetic (PBPK) models for each drug.
Specific Aim 2: Develop and validate amoxicillin and cephalexin dried-blood spot assays.
Specific Aim 3: Perform PD modeling 3A: Perform PD modeling (including Monte Carlo simulation) to evaluate the expected PK/PD target attainment of amoxicillin and cephalexin by age group.
3B: Identify a minimum trough threshold needed to establish 95% target attainment.
Exploratory Aim: Correlate patient genotype for H(+)/peptide transporters (PEPT) 1 and 2 and the organic-anion-transporting polypeptide (OATP) family of transporters with patient-specific PK parameters.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Amoxicillin - standard-of-care dose | No intervention | –Obtain amoxicillin plasma concentrations in patients already receiving amoxicillin |
| Cephalexin - standard-of-care dose | No intervention | –Obtain cephalexin plasma concentrations in patients already receiving cephalexin |
| Amoxicillin - study dose | Experimental | Drug: AmoxicillinObtain amoxicillin plasma concentrations after a study-administered dose of amoxicillin |
| Cephalexin - study dose | Experimental | Drug: CephalexinObtain cephalexin plasma concentrations after a study-administered dose of cephalexin |
Who may qualify
- Ages
- 1 day to 60 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Patients admitted to Children's Hospital Colorado derived from two groups:
Key exclusion criteria (1 listed)
- Across both groups, exclusion criteria are: (1) weight <2kg, (2) renal dysfunction, including the use of any renal replacement therapy, (3) significant β-lactam allergy, (4) GI disorders significantly impairing drug absorption, (5) use of external circuits that would affect the study drug's volume of distribution (e.g. ECMO), and (6) clinically significant anemia precluding study-related blood draws.
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 |
|---|---|---|
| Amoxicillinoral one-time dose of amoxicillin | Drug | Amoxicillin - study dose |
| Cephalexinoral one-time dose of cephalexin | Drug | Cephalexin - study dose |
Primary outcome
Time above Minimum Inhibitory Concentration (T > MIC)
Time frame: up to 24 hours
As a surrogate of treatment efficacy for amoxicillin and cephalexin, the investigators will determine the time that free plasma concentrations (fT > MIC) of amoxicillin and cephalexin remain above the minimum inhibitory concentration (MIC) of common neonatal pathogens. Monte Carlo simulation will be used to assess for the likelihood of fT > MIC dosing goals.
7 secondary outcomes
Clearance (CL/F) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Volume of Distribution (V/F) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Half life (T1/2) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Area under the curve (AUC) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Peak serum drug concentration (Cmax) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Minimum serum drug concentration (Cmin) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Time at which maximal drug concentration is achieved (Tmax) of amoxicillin and cephalexin
Time frame: Plasma drug concentrations obtained within 12 hours of a dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Individual participant dataSharing planned: No
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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.
Andrew Haynes, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Amoxicillin and Cephalexin in people with Neonatal Infection, run by University of Colorado, Denver at 1 site in United States.
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 1 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 19 May 2026. 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 States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time above Minimum Inhibitory Concentration (T > MIC) (time frame: up to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 May 2026.