TLC590 for Postoperative Pain

Recruiting at 1 trial location

Overseen By Grace Tsao

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taiwan Liposome Company

Must not be taking: Anticonvulsants, Antiarrhythmics, Opioids, others

Disqualifiers: Seizures, Cardiac arrhythmia, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 2 open-label trial investigates the pharmacokinetics (PK), pharmacodynamics, and safety profile of TLC590 across various surgical procedures. Researchers aim to determine the maximum tolerated dose (MTD) of TLC590 via Safety Monitoring Committee (SMC). The study evaluates TLC590 in bunionectomy, laparoscopy-assisted open ventral hernia repair, breast augmentation, abdominoplasty, and total knee arthroplasty models. Additionally, it determines the relative bioavailability of TLC590 to ropivacaine injection.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications, especially those related to seizures, cardiac arrhythmias, and daily analgesics, may affect eligibility, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug TLC590 for postoperative pain?

Research shows that ropivacaine, a component of TLC590, can help reduce pain after surgeries like breast cancer surgery and spine fusion surgery. In these studies, ropivacaine was effective in lowering pain scores and reducing the need for additional pain medication. ^{1 2 3 4 5}

Is TLC590 (Ropivacaine Extended-Release Injectable Suspension) safe for humans?

Ropivacaine, the active ingredient in TLC590, is generally considered safer than similar drugs, but there have been reports of seizures and convulsions when administered incorrectly or in high doses. It is important to follow proper administration guidelines to minimize risks. ^{6 7 8 9 10}

How is the drug TLC590 different from other treatments for postoperative pain?

TLC590 is unique because it is an extended-release formulation of ropivacaine, designed to provide long-lasting pain relief after surgery, unlike standard ropivacaine which only lasts for several hours. ^{1 2 7 11 12}

Research Team

Tien-Tzu Tai, MD

Principal Investigator

Taiwan Liposome Company

Eligibility Criteria

This trial is for individuals undergoing certain surgeries (like bunionectomy, hernia repair, breast augmentation, tummy tuck, or knee replacement) who need pain management post-operation. Specific eligibility criteria are not provided here.

Inclusion Criteria

I am not pregnant and follow the required birth control measures.

BMI >18 and ≤39 kg/m2

Able and willing to provide written informed consent

Exclusion Criteria

I have not had cancer in the last 2 years, with some exceptions.

I have a history of irregular heartbeats or take medication for it.

History of suicidal behavior or positive test results for specific infections

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TLC590 or ropivacaine injection across various surgical models to evaluate pharmacokinetics, pharmacodynamics, and safety

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TLC590

Trial Overview The study is testing TLC590 to see how it's processed in the body and its safety across different surgeries. It compares TLC590 with a standard pain relief injection called ropivacaine to find the highest dose patients can tolerate without severe side effects.

Participant Groups

Group I: Part 3, Cohort 8 Experimental Treatment 1 Intervention

Abdominoplasty: The MTD of TLC590

Group II: Part 3, Cohort 7 Experimental Treatment 1 Intervention

Total Knee Arthroplasty: The MTD of TLC590

Group III: Part 3, Cohort 6 Experimental Treatment 1 Intervention

Laparoscopy-assisted Open Ventral Hernia: The MTD of TLC590

Group IV: Part 2, Cohort 5 Experimental Treatment 1 Intervention

Breast Augmentation: TLC590 with the SMC-suggested dose

Group V: Part 2, Cohort 4 Experimental Treatment 2 Interventions

Breast Augmentation: TLC590 or Ropivacaine

Group VI: Part 2, Cohort 3 Experimental Treatment 2 Interventions

Breast Augmentation: TLC590 or Ropivacaine

Group VII: Part 1, Cohort 2 Experimental Treatment 1 Intervention

Laparoscopy-assisted Open Ventral Hernia: TLC590

Group VIII: Part 1, Cohort 1 Experimental Treatment 1 Intervention

Bunionectomy: Increasing dose cohorts for TLC590

Who Is Running the Clinical Trial?

Taiwan Liposome Company

Lead Sponsor

Trials

19

Recruited

1,800+

Findings from Research

In a study involving 81 patients, infiltration of ropivacaine did not significantly reduce acute pain after breast cancer surgery compared to a placebo, as measured by pain scores and medication use.

One year later, there was no difference in the incidence of chronic pain between the ropivacaine and placebo groups, indicating that ropivacaine scar infiltration was ineffective for both acute and chronic pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ropivacaine infiltration during breast cancer surgery: postoperative acute and chronic pain effect]. Baudry, G., Steghens, A., Laplaza, D., et al.[2022]

In a pilot study involving postoperative patients after total knee arthroplasty, an intraarticular injection of 100 mL of 0.2% ropivacaine showed a trend towards lower pain scores compared to placebo, but this was not statistically significant.

Despite the initial trend in pain reduction, the use of ropivacaine did not lead to a significant decrease in narcotic usage, indicating that it may not be an effective standalone treatment for pain management after knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of intraarticular ropivacaine for pain management immediately following total knee arthroplasty. Rosen, AS., Colwell, CW., Pulido, PA., et al.[2021]

Infusing ropivacaine at the port sites after laparoscopic cholecystectomy significantly reduced postoperative pain scores at 1 hour and at discharge compared to normal saline, indicating its efficacy in pain management.

Patients receiving ropivacaine also required less meperidine for pain relief and had shorter hospital stays, suggesting that this local anesthesia technique can enhance recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local anesthesia with ropivacaine for patients undergoing laparoscopic cholecystectomy. Liu, YY., Yeh, CN., Lee, HL., et al.[2022]

Continuous wound infusion of ropivacaine significantly reduced postoperative pain scores and opioid consumption in 60 patients after open hepatectomy, leading to better pain management.

Patients receiving ropivacaine also experienced faster bowel recovery and shorter hospital stays, with no reported surgical wound infections, indicating that this method is both safe and effective for enhancing recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of postoperative continuous wound infiltration with local anesthesia after open hepatectomy]. Yu, H., Li, ZY., Yu, X.[2018]

In a study of 38 patients undergoing spine stabilization surgery, continuous wound instillation of ropivacaine significantly reduced pain scores and the need for additional pain medication compared to standard IV morphine and ketorolac treatment.

The use of ropivacaine not only improved pain management but also resulted in less postoperative blood loss and a shorter hospital stay, with no observed toxic side effects, indicating its safety and efficacy for postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery. Bianconi, M., Ferraro, L., Ricci, R., et al.[2022]

In a study involving continuous infusion of ropivacaine after colon cancer surgery, the maximum unbound ropivacaine concentration was significantly below the toxicity threshold, indicating a strong safety profile for this pain management approach.

The infusion of ropivacaine for 96 hours was found to be a safe alternative to standard opioid analgesia, potentially reducing opioid-related side effects and improving patient recovery, while also suggesting that higher doses could be tested for better pain control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 96-hour incision-site continuous infusion of ropivacaine for postoperative analgesia after bowel cancer resection. Corso, OH., Morris, RG., Hewett, PJ., et al.[2018]

A case report of a 75-year-old woman showed that despite the general safety profile of ropivacaine, it can still cause serious side effects like convulsions immediately after epidural administration, highlighting the need for caution in elderly patients.

The patient experienced a generalized tonic-clonic convulsion but recovered well after treatment, indicating that while ropivacaine is associated with good cardiovascular stability, there remains a risk of inadvertent intravascular injection during epidural procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ropivacaine-induced convulsion immediately after epidural administration--a case report. Cherng, CH., Wong, CS., Ho, ST.[2018]

Ropivacaine is generally considered safer than bupivacaine due to its lower systemic toxicity, but this case highlights that it can still cause serious side effects, such as seizures.

In a reported case, a patient experienced a seizure after receiving 120 mg of ropivacaine intravenously, indicating that while the risk is lower, systemic toxicity can still occur with ropivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ropivacaine-induced seizure after extradural anaesthesia. Abouleish, EI., Elias, M., Nelson, C.[2019]

In a study of 24 patients across three age groups, it was found that older patients (aged 61 and above) had a significantly longer elimination half-life and decreased clearance of ropivacaine after epidural administration, indicating that age affects the drug's pharmacokinetics.

Despite these age-related differences in absorption and elimination, the study concluded that they are unlikely to increase the risk of systemic toxicity from a single epidural dose of ropivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of age on the systemic absorption and systemic disposition of ropivacaine after epidural administration. Simon, MJ., Veering, BT., Vletter, AA., et al.[2018]

A case report describes a patient who experienced withdrawal symptoms after a continuous epidural analgesia with ropivacaine was abruptly stopped, highlighting the potential for withdrawal effects from this local anesthetic.

The symptoms of agitation, tremors, tachycardia, and tachypnea resolved quickly after re-administering ropivacaine, suggesting that prolonged use may lead to physiological changes, such as upregulation of sodium channels, which could contribute to withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ropivacaine withdrawal syndrome: a case report]. Viderman, D., Portnyagin, I., la Fleur, P., et al.[2022]

A new long-acting formulation of ropivacaine was developed using a self-assembling peptide, which allows for a slow release of the drug, significantly extending its analgesic effects compared to conventional ropivacaine.

In rodent models, this nanocrystal formulation provided effective pain relief without causing local toxicity, suggesting it could be a safe and effective option for long-term postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction Between Ropivacaine and a Self-Assembling Peptide: A Nanoformulation for Long-Acting Analgesia. Peng, F., Liu, J., Zhang, Y., et al.[2022]

In a study of 310 patients undergoing major abdominal colorectal surgery, continuous wound infusion of ropivacaine provided minimal benefit compared to saline, showing no significant differences in pain management or recovery outcomes.

While there was a slight reduction in pain on movement on Day 1 for the ropivacaine group, this effect was not sustained beyond the first day, indicating that a multimodal approach to pain management remains the most effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous wound infusion of local anesthetic for the control of pain after elective abdominal colorectal surgery. Polglase, AL., McMurrick, PJ., Simpson, PJ., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

[Ropivacaine infiltration during breast cancer surgery: postoperative acute and chronic pain effect]. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of intraarticular ropivacaine for pain management immediately following total knee arthroplasty. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Local anesthesia with ropivacaine for patients undergoing laparoscopic cholecystectomy. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Efficacy of postoperative continuous wound infiltration with local anesthesia after open hepatectomy]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of 96-hour incision-site continuous infusion of ropivacaine for postoperative analgesia after bowel cancer resection. [2018]

7. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Ropivacaine-induced convulsion immediately after epidural administration--a case report. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Ropivacaine-induced seizure after extradural anaesthesia. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

The effect of age on the systemic absorption and systemic disposition of ropivacaine after epidural administration. [2018]

10. Brazil pubmed.ncbi.nlm.nih.gov

[Ropivacaine withdrawal syndrome: a case report]. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Interaction Between Ropivacaine and a Self-Assembling Peptide: A Nanoformulation for Long-Acting Analgesia. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Continuous wound infusion of local anesthetic for the control of pain after elective abdominal colorectal surgery. [2018]