Clinical trial NCT04294862: Tissue Distribution, Pharmacokinetics, Safety, and Tolerability After a Single Dose of TNP-2092 in Participants Undergoing Primary Total Hip or Knee Arthroplasty
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prosthetic Joint Infection
Keywords: TNP-2092
tissue distribution
THA
TKA
safety
PK
Lead sponsor: TenNor Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-04
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Concentration of TNP-2092 in synovial fluid
timeFrame: 2 hours after infusion
measure: Concentration of TNP-2092 in bone
timeFrame: 2 hours after infusion
Secondary outcomes:
measure: Plasma PK of a single IV dose of TNP-2092
timeFrame: pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion
measure: Plasma PK of a single IV dose of TNP-2092
timeFrame: pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion
measure: Plasma PK of a single IV dose of TNP-2092
timeFrame: pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion
measure: Plasma PK of a single IV dose of TNP-2092
timeFrame: pre-dose, end of infusion, 1 hours, 3 hous, 6 hours, 12 hours and 24 hours after infusion
measure: Rate of adverse event with TNP-2092
timeFrame: Day2, Day7, Day14
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Rothman Orthopedic Institute
state: Pennsylvania
Study officials:
References: