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

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

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.

Study Overview

• Status: Completed
• Conditions: Prosthetic Joint Infection
• Intervention / Treatment: Drug: TNP-2092

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Rothman Orthopedic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TNP-2092 300mg IV; TNP-2092 for injection 100mg/vial, 300mg, BID, 1 dose	Drug: TNP-2092; TNP-2092 for injection 100mg/vial; Other Names: CBR-2092

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TenNor Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2021
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): June 29, 2022

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: March 1, 2020
• First Posted (ACTUAL): March 4, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: safety; PK; THA; TKA; TNP-2092; tissue distribution
• Other Study ID Numbers: PJI001-04

Drug and device information, study documents

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