An Open-Label Ascending Dose Pharmacokinetic, Safety and Tolerability Study of Treatment with TKAine System (Bupivacaine HCl Monohydrate) After Total Knee Arthroplasty (TKA)
- Conditions
- Post-operative pain in patients following Total Knee Arthroplasty (TKA) proceduresAnaesthesiology - Pain management
- Registration Number
- ACTRN12619000775112
- Lead Sponsor
- Foundry Therapeutics 1, Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 22
1. Male or female, greater than or equal to 18 and less than or equal to 80 years of age at the Screening Visit.
2. Female subjects only: Postmenopausal, surgically sterile, or willing to use acceptable means of contraception from the Screening Visit through the Final Follow-up Visit. Medically acceptable methods of contraception that may be used by the subject include birth control pills, diaphragm with spermicide, intrauterine device (IUD), condom with spermicide, vaginal spermicidal suppository, or progestin implant or injection (used consistently for more than or equal to 3 months at the time of screening). Female subjects who are not of child bearing potential must have a medical history recorded of surgical sterilization (more than or equal to 6 months post-surgery at the time of screening) or post-menopausal (not experienced a menstrual period more than or equal to 2 years at the time of screening).
3. Scheduled to undergo primary unilateral TKA under anesthesia.
4. American Society of Anesthesiology (ASA) Physical Classification System class 1-2. ASA 3 is permitted if BMI is the only reason for classifying as ASA 3.
5. Primary indication of surgical procedure is knee pain.
6. Able and willing to comply with all study visits and procedures.
7. Willing and capable of providing written informed consent.
1. Has a planned concurrent surgical procedure (e.g., bilateral TKA).
2. Has had any previous arthroplasty, unicompartmental knee arthroplasty or TKA in the study knee.
3. Has varus more than 10° and valgus more than 15°.
4. Has a pre-existing concurrent acute or chronic painful physical condition for which they routinely take narcotic analgesics other than for surgical knee.
5. Has a contraindication or a known or suspected history of hypersensitivity or idiosyncratic reaction to required study medications including surgical medications such as anesthesia.
6. Unable to abstain from opioid use for knee pain (including codeine) within 2 weeks (14 days) of surgery.
7. Has taken NSAIDs within 7 days prior to the scheduled surgery. (Does not include Celecoxib on day of surgery).
8. Has been administered any anesthetic including but not limited to bupivacaine, ropivacaine or lidocaine within 5 days prior to the scheduled surgery.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall PK parameters for plasma bupivacaine include AUC¬0-24¬, AUC0-infinity, Cmax, tmax, and t1/2; and dose specific PK parameters include Cmax, tmax, and AUC.[Plasma PK samples will be taken at baseline (prior to TKAine placement) and after TKAine placement on Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21, 24, 27, 30, 45 and 60]
- Secondary Outcome Measures
Name Time Method The time to ambulate is the first time the subject first gets out of bed. The time will be assessed by direct observation and comparing the time the subject first gets out of bed compared to the time of surgical closure.<br>[This data is collected within 24hrs after surgery.];Safety and tolerability will be assessed by PK concentration, adverse events, and electrocardiograms.<br><br>Potential adverse events may include cardiotoxicity and neurotoxicity. Adverse events data will be collected using medical records, participant reported outcomes, and direct observations.<br>[Study Assessments will be taken at baseline (prior to TKAine placement) and after TKAine placement on Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21, 24, 27, 30, 45 and 60.]