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Trial registered on ANZCTR


Registration number
ACTRN12619000775112
Ethics application status
Approved
Date submitted
15/05/2019
Date registered
24/05/2019
Date last updated
5/09/2019
Date data sharing statement initially provided
24/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open-Label Ascending Dose Pharmacokinetic, Safety and Tolerability Study of Treatment with TKAine System (Bupivacaine HCl Monohydrate) After Total Knee Arthroplasty (TKA)
Scientific title
An Open-Label Ascending Dose Pharmacokinetic, Safety and Tolerability Study of Treatment with TKAine System (Bupivacaine HCl Monohydrate) After Total Knee Arthroplasty (TKA)
Secondary ID [1] 298250 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative pain in patients following Total Knee Arthroplasty (TKA) procedures 312846 0
Condition category
Condition code
Anaesthesiology 311350 311350 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
TKAine is a bupivacaine HCl-releasing bioresorbable implant system that is placed within the knee capsule after a Total Knee Arthroplasty procedure at the time of surgery and prior to surgical closure of the knee capsule. Each TKAine depot is an implant that delivers bupivacaine drug with a polymer matrix that bioresorbs over time.

This is a dose ascending study where the total dose for each cohort is administered at one time at the time of surgery by an orthopaedic surgeon. The starting dose is 300 mg bupivacaine hydrochloride monohydrate. The escalation schedule will be determined by the Data Safety Monitoring Board (DSMB) and can be escalated up to 8 TKAine depots at a total dose of 2400 mg bupivacaine hydrochloride monohydrate. Each cohort will be assessed by the DSMB prior to initiating the next cohort.

Up to four total dose levels will be assessed. A minimum of 3 subjects will be enrolled in each of Cohort 1 and Cohort 2. A minimum of 6 subjects will be enrolled in each of Cohort 3 and Cohort 4. No more than 30 total subjects will be enrolled in the study from all the Cohorts combined.
Intervention code [1] 314489 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320079 0
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.
Timepoint [1] 320079 0
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, 30, 45 and 60.
Secondary outcome [1] 370458 0
Safety and tolerability will be assessed by PK concentration, adverse events, and electrocardiograms.

Potential adverse events may include cardiotoxicity and neurotoxicity. Adverse events data will be collected using medical records, participant reported outcomes, and direct observations.
Timepoint [1] 370458 0
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, 30, 45 and 60.
Secondary outcome [2] 370459 0
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.
Timepoint [2] 370459 0
This data is collected within 24hrs after surgery.

Eligibility
Key inclusion criteria
1. Male or female, greater than or equal to 18 and less than or equal to 75 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.
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.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has a planned concurrent surgical procedure (e.g., bilateral TKA).
2. Has had any previous arthroplasty, unicompartmental knee arthroplasty or TKA in either 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Dose-ascending study by cohort. Each patient within a cohort will receive equivalent dosing.
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
None

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13760 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 26509 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 302790 0
Commercial sector/Industry
Name [1] 302790 0
Foundry Therapeutics 1, Pty Ltd
Address [1] 302790 0
Level 19 HWT Tower
40 City Road
Southbank, VIC 3006
Country [1] 302790 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Foundry Therapeutics 1, Pty Ltd
Address
Level 19 HWT Tower
40 City Road
Southbank, VIC 3006
Country
Australia
Secondary sponsor category [1] 302736 0
None
Name [1] 302736 0
None
Address [1] 302736 0
None
Country [1] 302736 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303381 0
Bellberry HREC
Ethics committee address [1] 303381 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 303381 0
Australia
Date submitted for ethics approval [1] 303381 0
15/05/2019
Approval date [1] 303381 0
05/07/2019
Ethics approval number [1] 303381 0

Summary
Brief summary
The primary objective of the study is to determine the amount of bupivacaine in the blood for adult subjects undergoing a total knee arthroplasty.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93474 0
Dr David Broe
Address 93474 0
Prince of Wales Public Hospital
320-346 Barker Street
Randwick, NSW 2031
Country 93474 0
Australia
Phone 93474 0
+61 0296504397
Fax 93474 0
Email 93474 0
dbroeortho@gmail.com
Contact person for public queries
Name 93475 0
Mrs Melinda Morrell
Address 93475 0
Foundry Therapeutics 1, Pty Ltd
Level 19 HWT Tower
40 City Road
Southbank, VIC 3006
Country 93475 0
Australia
Phone 93475 0
+61 0488844056
Fax 93475 0
Email 93475 0
melinda@thefoundry.com
Contact person for scientific queries
Name 93476 0
Mrs Melinda Morrell
Address 93476 0
Foundry Therapeutics 1, Pty Ltd
Level 19 HWT Tower
40 City Road
Southbank, VIC 3006
Country 93476 0
Australia
Phone 93476 0
+61 0488844056
Fax 93476 0
Email 93476 0
melinda@thefoundry.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is an early assessment of the safety and tolerability of a novel product for which sharing of data would not be useful to existing commercial products or pain management approaches.
What supporting documents are/will be available?
No other documents available
Summary results
No Results