Pharmacokinetics and Safety of Cefazolin 3gm DUPLEX in Adults

NCT05205486 | Completed Phase 1 Results FDA Drug

• 1 other identifier: US-G-H-2101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Infections

Keywords

Cephalosporin; antibiotic; infection control; surgical prophylaxis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (39)

• Number of Participants With Treatment-Emergent Adverse Events [Safety] According to Study Protocol

  2 days with optional visit on Day 8

• Hematology: Hemoglobin (Hb)

  2 days with optional visit on Day 8

• Hematology: Hematocrit (Hct)

  2 days with optional visit on Day 8

• Hematology: Mean Corpuscular Volume (MCV)

  2 days with optional visit on Day 8

• Hematology: Mean Corpuscular Hemoglobin (MCH)

  2 days with optional visit on Day 8

Study Arms (1)

Cefazolin 3gm Injection

EXPERIMENTAL

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

Interventions

Cefazolin 3gm for Injection USP and Dextrose Injection USP DRUG

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

Also known as: Cefazolin 3gm in DUPLEX (50ml)

Cefazolin 3gm Injection

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• If female, is pregnant or lactating/breastfeeding.
• 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.
• 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)
• 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.
• 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.
• Has had a recent (within 14 days prior to the planned surgery) administration of cefazolin.
• 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.
• Has a known history of human immunodeficiency virus, hepatitis B, or hepatitis C infection.
• Has a current history of medical condition(s), which in the opinion of the investigator, would interfere with the evaluation of the study treatment.
• Has a known history of organ transplant.
• Has a clinically relevant disease/dysfunction of or a history of severe cardiac, pulmonary or hepatic disease.
• 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.
• Has received any other investigational drug/device within 30 days prior to the study treatment administration.
• Has any planned medical intervention or personal event that might interfere with ability to comply with the study requirements.
• 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.

Sponsors & Collaborators

• B. Braun Medical Inc.: lead

Study Sites (2)

IACT Health - Roswell - IACT - HyperCore - PPDS

Columbus, Georgia, 31904, United States

Location

Hightower Clinical, LLC

Oklahoma City, Oklahoma, 73102, United States

Location

Related Publications (11)

• 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.

  PMID: 12698406 BACKGROUND

• 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.

  PMID: 26971263 BACKGROUND

• 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.

  PMID: 4201317 BACKGROUND

• 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.

  PMID: 3437384 BACKGROUND

• 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.

  PMID: 7603806 BACKGROUND

• 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.

  PMID: 2644371 BACKGROUND

• 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.

  PMID: 12400768 BACKGROUND

• 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.

  PMID: 9261702 BACKGROUND

• 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.

  PMID: 877649 BACKGROUND

• 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.

  PMID: 25941220 BACKGROUND

• 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.

  PMID: 33202066 BACKGROUND

Related 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

MeSH Terms

Conditions

Infections

Results Point of Contact

• Title: Director, Scientific Affairs Operations
• Organization: B. Braun Medical Inc.

kevin.minnich@bbraunusa.com

610-596-2512

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label, non-randomized pharmacokinetic study. All subjects will be receiving the same study treatment, thus masking is unnecessary.
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, non-randomized pharmacokinetic study. All subjects will be receiving the same study treatment, thus blinding is unnecessary.

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: January 25, 2022
• Study Start: April 5, 2022
• Primary Completion: July 13, 2023
• Study Completion: July 13, 2023
• Last Updated: February 28, 2025
• Results First Posted: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)