Pharmacokinetics (PK) of Antistaphylococcal Antibiotics in Infants (NICHD-2012-02-Staph Trio)

NCT01728363 | Completed Phase 1 DMC

• 1 other identifier: Pro00037820
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 10

Brief Summary

Multiple center, open-label, PK study

Conditions

Systemic Infection

Keywords

Staphylococcal

Outcome Measures

Primary Outcomes (4)

• Cohort 1: Area under the curve infinity (AUCinfinity) for rifampin

  Pharmacometric analysis of area under the curve at steady state for cohort 1 participants who were dosed with rifampin 10mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

  72 hours

• Cohort 1: Maximum concentration (Cmax) of rifampin

  Pharmacometric analysis of maximum concentration after first dose for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

  72 hours

• Cohort 1: Clearance (CL) of rifampin

  Pharmacometric analysis of the clearance for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

  72 hours

• Cohort 1: Volume of distribution at steady state (Vss) of rifampin

  Pharmacometric analysis of volume of distribution at steady state for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

  72 hours

Secondary Outcomes (2)

• Cohort 1: Adverse events for participants receiving rifampin

  7 days after last study dose

• Cohort 1 participants: serious adverse events for participants receiving rifampin

  7 days after last study dose

Study Arms (3)

Ticarcillin-clavulanate antibiotic

EXPERIMENTAL

Cohort Gestational Age (GA) Postnatal Age (PNA) Dose 1. \<30 weeks \<14 days: 75 mg/kg Q12 hrs x 6 doses 2. \<30 weeks ≥14 days-45 days 75 mg/kg Q 8 hours x 6 doses 3. \<30 weeks \>45 days-90 days 75 mg/kg Q 6 hours x 6 doses Brand name is Timentin. This drug is an antibiotic used to treat a wide variety of bacterial infections. It is a combination of two drugs \& both treat bacterial infections. Ticarcillin is a penicillin-type antibiotic that stops bacterial growth \& clavulanate potassium is an enzyme inhibitor that helps the ticarcillin work better.

Drug: Antibiotic

Rifampin generic antibiotic

EXPERIMENTAL

Cohort GA PNA Dose 1. \<32 weeks \<14 days 10 mg/kg Q 24 hours x 4 doses 2. \<32 weeks ≥14 days-120 days 15 mg/kg Q 24 hours x 4 doses 3. ≥32 weeks \<14 days 15 mg/kg Q 24 hours x 4 doses 4. ≥32 weeks ≥14 days-120 days 20 mg/kg Q 24 hours x 4 doses The brand name is Rifadin, Rimatane. This drug is an antibiotic and a first line antituberculotic and unlabeled use for infections caused by staphylococcus aureus \& staphylococcus epidermis.

Drug: Antibiotic

Clindamycin Generic Antibiotic

EXPERIMENTAL

Cohort GA PNA Dose 1. \<30 weeks \<14 days 10 mg/kg Q 12 hours x 6 doses 2. \<30 weeks ≥14 days-45 days 10 mg/kg Q 8 hours x 6 doses 3. \<30 weeks \>45 days-120 days 10 mg/kg Q 6 hours x 6 doses The brand name is Cleocin. This drug is an antibiotic used to treat a wide variety of bacterial infections and serious infections.

Drug: Antibiotic

Interventions

Antibiotic DRUG

Ticarcillin-clavulanate/Timentin is an antibiotic used to treat a wide variety of bacterial infections. Rifampin/Rifadin/Rimatane is an antibiotic and first line antituberculotic. Clindamycin/Cleocin is an antibiotic used to treat a wide variety of bacterial infections and serious bacterial infections.

Also known as: Ticarcillin-clavulanate generic; Brand Timentin, Rifampin generic; Brand Rifadin, Rimatane, Clindamycin generic; Brand Cleocin

Clindamycin Generic Antibiotic; Rifampin generic antibiotic; Ticarcillin-clavulanate antibiotic

Eligibility Criteria

• Age: 14 Days - 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Sufficient intravascular access
• Suspected systemic infection or receiving 1 of the study drugs per standard of care
• informed consent from legal guardian

You may not qualify if:

• history of allergic reaction to study drugs
• urine output \<0.5 mL/hr/kg over the prior 24 hours
• serum creatinine \>1.7 mg/dl
• Any condition in investigator judgment precludes participation because it could affect participant safety

Sponsors & Collaborators

• Phillip Brian Smith: lead

Study Sites (10)

University of FL

Gainesville, Florida, 32610, United States

Location

UFL Health and Baptist

Jacksonville, Florida, 32209, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Wesley Medical

Wichita, Kansas, 67214, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Kings County Hospital Center

Brooklyn, New York, 11203, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University of Texas Children's Hospital

Galveston, Texas, 77555, United States

Location

Related Publications (5)

• Maharaj AR, Gonzalez D, Cohen-Wolkowiez M, Hornik CP, Edginton AN. Improving Pediatric Protein Binding Estimates: An Evaluation of alpha1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet. 2018 May;57(5):577-589. doi: 10.1007/s40262-017-0576-7.

  PMID: 28779462 BACKGROUND

• Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM. Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2888-94. doi: 10.1128/AAC.03086-15. Print 2016 May.

  PMID: 26926644 RESULT

• Smith PB, Cotten CM, Hudak ML, Sullivan JE, Poindexter BB, Cohen-Wolkowiez M, Boakye-Agyeman F, Lewandowski A, Anand R, Benjamin DK Jr, Laughon MM; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Rifampin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2019 May 24;63(6):e00284-19. doi: 10.1128/AAC.00284-19. Print 2019 Jun.

  PMID: 30910891 RESULT

• Watt KM, Hornik CP, Balevic SJ, Mundakel G, Cotten CM, Harper B, Benjamin DK Jr, Anand R, Laughon M, Smith PB, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Pharmacokinetics of ticarcillin-clavulanate in premature infants. Br J Clin Pharmacol. 2019 May;85(5):1021-1027. doi: 10.1111/bcp.13882. Epub 2019 Mar 6.

  PMID: 30710387 RESULT

• Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Clindamycin in Obese and Nonobese Children. Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02014-16. doi: 10.1128/AAC.02014-16. Print 2017 Apr.

  PMID: 28137820 RESULT

MeSH Terms

Conditions

Toxemia

Interventions

Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Infections

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Philip B Smith, MD

  Duke Clinical Research Institute and DUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 9, 2012
• First Posted: November 19, 2012
• Study Start: January 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

US (10)