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

Phase 1

Completed

• Conditions: Prosthetic Joint Infection
• Interventions: Drug: TNP-2092

• Registration Number: NCT04294862
• Lead Sponsor: TenNor Therapeutics Limited

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-02-25
• Study First Submitted QC: 2020-03-01
• Study First Posted: 2020-03-04
• Study Start: 2021-03-01
• Primary Completion: 2021-12-31
• Study Completion: 2022-06-29
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-18
• Last Update Posted: 2022-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Participants are eligible to be included in the study only if all inclusion criteria are met:

1. Male or females, 18 years of age or older
2. Participants who require primary THA or TKA
3. Body mass index (BMI) >=18 kg/m2 but <=40 kg/m2
4. Capable of giving signed informed consent

Exclusion Criteria

Participants are excluded from the study if any of the following exclusion criteria are met:

1. History or hypersensitivity or intolerability to any of the following drugs: any member of fluoroquinolones, rifamycin, cefazolin or TNP-2092
2. History of known methicillin-resistant Staphylococcus aureus (MRSA) infections
3. 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;
4. Evidence of significant hepatic, hematologic or immunologic disease;
5. History or evidence of severe renal disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TNP-2092 300mg IV	TNP-2092	TNP-2092 for injection 100mg/vial, 300mg, BID, 1 dose

Primary Outcome Measures

Name	Time	Method
Concentration of TNP-2092 in synovial fluid	2 hours after infusion	Concentration in ng/mL
Concentration of TNP-2092 in bone	2 hours after infusion	Concentration in ng/g

Secondary Outcome Measures

Name	Time	Method
Rate of adverse event with TNP-2092	Day2, Day7, Day14	Description of adverse events as assessed by CTCAE 4.0
Plasma PK of a single IV dose of TNP-2092	pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion	AUC0-24: AUC versus time from time 0 to 24 hours, h\*ng/mL

Trial Locations

Locations (1)

Rothman Orthopedic Institute; 🇺🇸 Philadelphia, Pennsylvania, United States