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

Prosthetic Joint Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04294862
• Other study ID #: PJI001-04
• Status: Completed
• Phase: Phase 1
• Start date: March 1, 2021
• Est. completion date: June 29, 2022

Study information

• Verified date: October 2022
• Source: TenNor Therapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: June 29, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prosthetic Joint Infection

Intervention

Drug:
• TNP-2092
TNP-2092 for injection 100mg/vial

Locations

Country	Name	City	State
United States	Rothman Orthopedic Institute	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
TenNor Therapeutics Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of TNP-2092 in synovial fluid	Concentration in ng/mL	2 hours after infusion
Primary	Concentration of TNP-2092 in bone	Concentration in ng/g	2 hours after infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Rate of adverse event with TNP-2092	Description of adverse events as assessed by CTCAE 4.0	Day2, Day7, Day14