Pharmacokinetics and Safety of Cefazolin 3gm DUPLEX in Adults (3gCefPK)

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of a Single 3 Gram Dose of Cefazolin in Adult Subjects Weighing >= 120 kg Scheduled for Surgery

This study is designed to evaluate the pharmacokinetics (PK) of a single 3 gm dose of cefazolin from a DUPLEX container, in adult subjects (weighing >/= 120 kg) scheduled for surgery. Cefazolin will be administered as a 30-minute intravenous (IV) infusion, per cefazolin Package Insert. Five PK samples per subject will be obtained up to 8 hours after dosing. These data will then be assessed by the validated Cefazolin PK Model to verify there are no significant PK changes within this study population.

Study Overview

• Status: Completed
• Conditions: Infections
• Intervention / Treatment: Drug: Cefazolin 3gm for Injection USP and Dextrose Injection USP

Detailed Description

This is a Phase 1, open-label, single-dose, multiple-center, study to determine the pharmacokinetics of a single 3 g dose of cefazolin administered as a 30 minute IV infusion prior to surgery in adult subjects weighing >/= 120 kg. Adult subjects will be enrolled in order to ensure at least 12 subjects complete the study. Enrollment will be competitive across the study sites. All subjects will have Screening and baseline evaluations performed to ensure their eligibility for the study The Screening Period is up to 30 days before administration of study drug on Day 1.

Study drug will be administrated as an infusion over 30 minutes starting approximately 0.5 hours before surgery begins and following institutional guidelines on Day 1 (day of surgery). Planned surgical procedures may be performed outpatient or inpatient and are expected to last no longer than 3 hours.

If the surgery is extended unexpectedly beyond the 3-hour limit, additional doses of study drug are permitted according to institutional guidelines. PK blood sample collection will continue after the administration of an additional dose of cefazolin. Safety in this population will also be assessed.

All subjects will have five (5) individual whole blood samples (4 mL each) collected for the estimation of cefazolin concentration in plasma at the following times after the start of the infusion: 0.5 (+/-10 min) end of infusion, 1 h (+/-15 min), 2 h (+/-15 min), 4 h (+/-15 min) and 8 h (+/-15 min).

Safety will be assessed by monitoring adverse events (AEs), physical examination, vital signs, and clinical laboratory tests. A follow-up visit will be performed on Day 8 (+/-1 day) for safety assessments.

A subject is considered a study completer if he/she has completed all study related procedures through the end of surgery and the required PK sample collections. It is highly preferred that the subjects also participate in the Day 8 (+/-1 day) Safety Follow-up. For subjects who withdraw or are withdrawn before study completion of the study, every effort will be made to perform all Safety Follow up procedures.

Any subject who withdraws or is withdrawn before collection of at least 4 of the 5 PK samples will not be consider as a PK completer. If necessary, additional subjects must be enrolled to ensure that there are at least 12 PK completers.

On Day 8 (+/-1 day), a Safety follow-up will be conducted. If this is an in-person visit, the following will be performed: vital signs, clinical laboratory tests, examination of the infusion site, review of AEs and concomitant medication. If an in-person visit is not possible, every effort will be made to contact the subject by phone and the subjects will be asked about any AEs and concomitant medication they may have taken.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Columbus, Georgia, United States, 31904
      • IACT Health - Roswell - IACT - HyperCore - PPDS
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Hightower Clinical, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female aged >/= 18 years;
2. Must weigh >/= 120 kg
3. Able to understand and sign the Informed Consent Form(s) (ICF);
4. Is scheduled for surgery that is expected to last less than 3 hours;
5. Is scheduled for any type of surgery where a single-dose perioperative cefazolin prophylaxis is appropriate.

Exclusion Criteria:

1. If female, is pregnant or lactating/breastfeeding.
2. If female that is of childbearing potential and sexually active, and is not using an effective method of birth control, e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or have a partner with a vasectomy.
3. Has a history of renal impairment -- Subject has an eGFR of <80 mL/min/1.73m2 performed at Screening as calculated by the following equation: 186 x (Creatinine/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black) (FDA Guidance for Industry Pharmacokinetics in Patients with Impaired Renal Function)
4. Has a known allergy or hypersensitivity to β lactam/cephalosporin antibiotics, corn products, or dextrose-containing products or solutions, or any of the other ingredients of Cefazolin for Injection United States Pharmacopeia (USP) and Dextrose Injection USP in DUPLEX.
5. Has a result of any laboratory test (or repeat test, if done), obtained as standard of care, that is outside the normal limit of the site's laboratory reference range AND is considered by the investigator to be clinically significant.
6. Has had a recent (within 14 days prior to the planned surgery) administration of cefazolin.
7. Has had administration of any medication (e.g., prescription, herbal, over-the-counter medication[s] or dietary supplements) known to interact with cefazolin within 5 days prior to the study treatment administration.
8. Has a known history of human immunodeficiency virus, hepatitis B, or hepatitis C infection.
9. Has a current history of medical condition(s), which in the opinion of the investigator, would interfere with the evaluation of the study treatment.
10. Has a known history of organ transplant.
11. Has a clinically relevant disease/dysfunction of or a history of severe cardiac, pulmonary or hepatic disease.
12. Is undergoing any cardiovascular procedure including, but not limited to, major cardiac surgery, cardiac catheterizations (including electrophysiology studies), ablations, automatic implantable cardioverter-defibrillator (AICD), and pacemaker.
13. Has received any other investigational drug/device within 30 days prior to the study treatment administration.
14. Has any planned medical intervention or personal event that might interfere with ability to comply with the study requirements.
15. The subject has any condition that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the data.
16. Is unable or unwilling to adhere to the study-specified procedures and restrictions.
17. Is an employee of the Sponsor, Investigator or study-center, has direct involvement in the study or other studies under the direction of that Investigator or study-center, or is a family member of the employees or the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cefazolin 3gm Injection; Study drug will be administrated as an infusion over 30 minutes starting approximately 0.5 hours before surgery begins and following institutional guidelines on Day 1 (day of surgery). All subjects will have five (5) individual whole blood samples (4 mL each) collected for the estimation of cefazolin concentration in plasma at the following times after the start of the infusion: 0.5 (+/-10 min) end of infusion, 1 h (+/-15 min), 2 h (+/-15 min), 4 h (+/-15 min), and 8 h (+/-15 min).

Drug: Cefazolin 3gm for Injection USP and Dextrose Injection USP; Cefazolin 3gm for Injection USP and Dextrose Injection USP in the DUPLEX® Drug Delivery System. Administration will occur once as a 30 minute IV infusion prior to surgery in adult subjects weighing >/= 120 kg; Other Names: Cefazolin 3gm in DUPLEX (50ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cefazolin Plasma Concentration Following Infusion	Concentrations will be determined through analysis of 5 blood samples drawn at 0.5 (end of infusion), 1, 2, 4, and 8 hours after the start of study drug infusion.	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematology: Hematocrit (Hct)		2 days with optional visit on Day 8
Clinical Chemistry: Sodium	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: Potassium	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: Chloride	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: Albumin	g/L	2 days with optional visit on Day 8
Clinical Chemistry: Calcium	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: Creatinine	micro-mol/L	2 days with optional visit on Day 8
Number of Participants With Treatment-Emergent Adverse Events [Safety] According to Study Protocol	Safety will be assessed by monitoring adverse events (AEs), physical examination, vital signs, and clinical laboratory tests.	2 days with optional visit on Day 8
Hematology: Hemoglobin (Hb)	gm/L	2 days with optional visit on Day 8
Hematology: Mean Corpuscular Volume (MCV)	fL	2 days with optional visit on Day 8
Hematology: Mean Corpuscular Hemoglobin (MCH)	pg	2 days with optional visit on Day 8
Hematology: Mean Corpuscular Hemoglobin Concentration	mmol/L	2 days with optional visit on Day 8
Hematology: Platelet Count	platelets / L	2 days with optional visit on Day 8
Hematology: RBC	cells/L	2 days with optional visit on Day 8
Hematology: WBC	cells/L	2 days with optional visit on Day 8
Clinical Chemistry: CO2 (Bicarbonate)	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: Glucose	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: ALT	IU/L	2 days with optional visit on Day 8
Clinical Chemistry: AST	IU/L	2 days with optional visit on Day 8
Clinical Chemistry: Creatine Phosphokinase (CPK)	ukat / L	2 days with optional visit on Day 8
Clinical Chemistry: Lactic Acid Dehydrogenase (LDH)	IU/L	2 days with optional visit on Day 8
Clinical Chemistry: Alkaline Phosphatase	IU/L	2 days with optional visit on Day 8
Clinical Chemistry: Uric Acid	umol/L	2 days with optional visit on Day 8
Clinical Chemistry: Phosphate	mmol/L	2 days with optional visit on Day 8
Clinical Chemistry: Total Protein	g/L	2 days with optional visit on Day 8
Clinical Chemistry: Total Bilirubin	micro-mol/L	2 days with optional visit on Day 8
Clinical Chemistry: Blood Urea Nitrogen	mmol/L	2 days with optional visit on Day 8
Vital Signs: Temperature	Degree centigrade	Baseline; post-infusion at 30-minutes, 2-hours, 4-hours, and 8-hours; post-surgery
Vital Signs: Blood Pressure (Systolic)	mm Hg	Baseline; post-infusion at 30-minutes, 2-hours, 4-hours, and 8-hours; post-surgery
Vital Signs: Heart Rate	Beats per minute	Baseline; post-infusion at 30-minutes, 2-hours, 4-hours, and 8-hours; post-surgery
Vital Signs: Respiratory Rate	Breaths per minute	Baseline; post-infusion at 30-minutes, 2-hours, 4-hours, and 8-hours; post-surgery
Vital Signs: Weight	kg	Baseline
Vital Signs: Height	cm	Baseline
Vital Signs: BMI	kg/cm^2	Baseline
ECG: PR Interval	msec	2 days
ECG: QRS Duration	msec	2 days
ECG: QT Interval	msec	2 days
Urine Pregnancy Test	(If appropriate) If positive, a confirmatory serum test will be performed.	Baseline
Vital Signs: Blood Pressure (Diastolic)	mm Hg	Baseline; post-infusion at 30-minutes, 2-hours, 4-hours, and 8-hours; post-surgery

Collaborators and Investigators

• Sponsor: B. Braun Medical Inc.

Publications and helpful links

General Publications

• Haessler D, Reverdy ME, Neidecker J, Brule P, Ninet J, Lehot JJ. Antibiotic prophylaxis with cefazolin and gentamicin in cardiac surgery for children less than ten kilograms. J Cardiothorac Vasc Anesth. 2003 Apr;17(2):221-5. doi: 10.1053/jcan.2003.51.
• Kamath VH, Cheung JP, Mak KC, Wong YW, Cheung WY, Luk KD, Cheung KM. Antimicrobial prophylaxis to prevent surgical site infection in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion: 2 doses versus antibiotics till drain removal. Eur Spine J. 2016 Oct;25(10):3242-3248. doi: 10.1007/s00586-016-4491-7. Epub 2016 Mar 12.
• Khan AJ. Clinical and laboratory evaluation of cefazolin: a new cephalosporin antibiotic in pediatric patients. Curr Ther Res Clin Exp. 1973 Oct;15(10):727-33. No abstract available.
• Koshida R, Nakashima E, Ichimura F, Nakano O, Watanabe R, Taniguchi N, Tsuji A. Comparative distribution kinetics of cefazolin and tobramycin in children. J Pharmacobiodyn. 1987 Sep;10(9):436-42. doi: 10.1248/bpb1978.10.436.
• Lee KR, Ring JC, Leggiadro RJ. Prophylactic antibiotic use in pediatric cardiovascular surgery: a survey of current practice. Pediatr Infect Dis J. 1995 Apr;14(4):267-9. doi: 10.1097/00006454-199504000-00004.
• Leggett JE, Fantin B, Ebert S, Totsuka K, Vogelman B, Calame W, Mattie H, Craig WA. Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models. J Infect Dis. 1989 Feb;159(2):281-92. doi: 10.1093/infdis/159.2.281.
• Maher KO, VanDerElzen K, Bove EL, Mosca RS, Chenoweth CE, Kulik TJ. A retrospective review of three antibiotic prophylaxis regimens for pediatric cardiac surgical patients. Ann Thorac Surg. 2002 Oct;74(4):1195-200. doi: 10.1016/s0003-4975(02)03893-6.
• Rodgers GL, Fisher MC, Lo A, Cresswell A, Long SS. Study of antibiotic prophylaxis during burn wound debridement in children. J Burn Care Rehabil. 1997 Jul-Aug;18(4):342-6. doi: 10.1097/00004630-199707000-00012.
• Ross S, Rodriguez W, Khan W. The cephalosporin antibiotics in pediatric practice. South Med J. 1977 Jul;70(7):855-61. doi: 10.1097/00007611-197707000-00026.
• Schmitz ML, Blumer JL, Cetnarowski W, Rubino CM. Determination of appropriate weight-based cutoffs for empiric cefazolin dosing using data from a phase 1 pharmacokinetics and safety study of cefazolin administered for surgical prophylaxis in pediatric patients aged 10 to 12 years. Antimicrob Agents Chemother. 2015 Jul;59(7):4173-80. doi: 10.1128/AAC.00082-15. Epub 2015 May 4.
• Schmitz ML, Rubino CM, Onufrak NJ, Martinez DV, Licursi D, Karpf A, Cetnarowski W. Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients. J Clin Pharmacol. 2021 May;61(5):666-676. doi: 10.1002/jcph.1785. Epub 2020 Dec 9.

Helpful Links

• Nahata MC, Winters CB, Powell DA. Variation in prophylactic antibiotic use in pediatric orthopedic surgery. Drug Intell Clin Pharm. 1985;19(11):834-6
• Nahata MC, Durrell DE, Ginn-Pease ME, et al. Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery. Eur J Drug Metab Pharmacokinet. 1991;16(1):49-52

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2022
• Primary Completion (Actual): July 13, 2023
• Study Completion (Actual): July 13, 2023

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: antibiotic; Cephalosporin; infection control; surgical prophylaxis
• Additional Relevant MeSH Terms: Infections; Anti-Bacterial Agents; Anti-Infective Agents; Cefazolin
• Other Study ID Numbers: US-G-H-2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No