Tissue Distribution, Pharmacokinetics, Safety, and Tolerability After a Single Dose of TNP-2092 in Participants Undergoing Primary Total Hip or Knee Arthroplasty

Study Overview
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Brief Summary
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This study will investigate TNP-2092 distribution into joint tissues in participants undergoing a total hip arthroplasty (THA) or a total knee arthroplasty (TKA). Tissue distribution is the primary objective, and plasma pharmacokinetics (PK), safety, and tolerability are secondary objectives.

Detailed Description
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This is a Phase 1, open-label study to evaluate the tissue distribution, plasma PK, safety, and tolerability after a single 300 mg intravenous (IV) dose of TNP-2092 administered before induction of anesthesia in adult participants undergoing THA or TKA. Sixteen patients who are scheduled to undergo primary THA or TKA will be enrolled. The enrolled participants who meet the inclusion/exclusion criteria will receive the study intervention (a single 300 mg IV dose of TNP-2092) 2 hours before induction of anesthesia on Day 1. Tissue samples from bone and synovial fluid will be collected during surgery and analyzed for TNP-2092 and cefazolin concentrations. Plasma samples will be collected on Day 1 and Day 2 for PK analysis. Safety and tolerability information will be collected on Day 1 and Day 2 at the clinical center, on Day 7 by phone, and on Day 14 at a final follow-up visit.

Official Title
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An Open-Label Study to Evaluate Tissue Distribution, Plasma Pharmacokinetics, Safety, and Tolerability After a Single Intravenous Dose of TNP-2092 in Adult Participants Undergoing Primary Total Hip or Knee Arthroplasty

Conditions
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Prosthetic Joint Infection

Intervention / Treatment
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* Drug: TNP-2092


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are eligible to be included in the study only if all inclusion criteria are met: Male or females, 18 years of age or older Participants who require primary THA or TKA Body mass index (BMI) >=18 kg/m2 but <=40 kg/m2 Capable of giving signed informed consent Exclusion Criteria: Participants are excluded from the study if any of the following exclusion criteria are met: History or hypersensitivity or intolerability to any of the following drugs: any member of fluoroquinolones, rifamycin, cefazolin or TNP-2092 History of known methicillin-resistant Staphylococcus aureus (MRSA) infections Presence of any surgical or medical condition that in the opinion of the principal investigator and the medical monitor that could impact the interpretation of the results of the study; Evidence of significant hepatic, hematologic or immunologic disease; History or evidence of severe renal disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNP-2092 300mg IV<br>TNP-2092 for injection 100mg/vial, 300mg, BID, 1 dose | Drug: TNP-2092<br>* TNP-2092 for injection 100mg/vial<br>* Other names: CBR-2092;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of TNP-2092 in synovial fluid | Concentration in ng/mL | 2 hours after infusion | 
| Concentration of TNP-2092 in bone | Concentration in ng/g | 2 hours after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma PK of a single IV dose of TNP-2092 | CTissue: Drug concentration in tissue, ng/mL | pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion | 
| Plasma PK of a single IV dose of TNP-2092 | Cmax: Peak plasma concentration,ng/mL | pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion | 
| Plasma PK of a single IV dose of TNP-2092 | Tmax: Time to maximum plasma concentration, hours | pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion | 
| Plasma PK of a single IV dose of TNP-2092 | AUC0-24: AUC versus time from time 0 to 24 hours, h*ng/mL | pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion | 
| Rate of adverse event with TNP-2092 | Description of adverse events as assessed by CTCAE 4.0 | Day2, Day7, Day14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TNP-2092, tissue distribution, THA, TKA, safety, PK