ATX101 for Postoperative Pain

(SPARK 2 Trial)

Overseen By Clinical Trial Lead

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Allay Therapeutics, Inc.

Must not be taking: Opioids, CBD oil, Kratom

Disqualifiers: High BMI, Recent knee surgery, others

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

Compensation: Varies

Number of Visits: 8

Duration: 1 week

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using medications or products that can impact pain control, like CBD oil or Kratom, from the screening visit until the last trial visit. You must also stop using opioids for knee pain at least 2 weeks before surgery.

What data supports the effectiveness of the drug ATX101 for postoperative pain?

Research shows that bupivacaine, a component of ATX101, can reduce pain and the need for narcotics after surgery, as seen in studies where patients had lower pain scores and used fewer painkillers compared to those given a placebo. ^{1 2 3 4 5}

Is ATX101 (Bupivacaine Hydrochloride) safe for use in humans?

Bupivacaine, used in various forms, has been studied for safety in humans. Some studies report that it can cause paraesthesia (a tingling or prickling sensation) when used as a local anesthetic, but it is generally considered safe for managing postoperative pain. ^{1 6 7 8 9}

How does the drug ATX101 for postoperative pain differ from other treatments?

ATX101 is unique because it combines bupivacaine hydrochloride, a long-acting local anesthetic, with a saline placebo, potentially offering a novel approach to managing postoperative pain without relying on opioids, unlike traditional treatments that often include opioid medications. ^{3 6 10 11 12}

What is the purpose of this trial?

The goal of the ATX101-TKA-004 clinical trial aims to evaluate the efficacy and safety of ATX101 1,500 mg in participants undergoing primary unilateral total knee arthroplasty. The study will compare the effectiveness of ATX101 with a saline placebo and bupivacaine, an active comparator. Additionally, it will assess opioid consumption among participants receiving ATX101 versus those given the saline placebo and bupivacaine. The trial will also focus on the safety and tolerability of ATX101 in the participants.

Research Team

David Hewitt, MD

Principal Investigator

Allay Therapeutics, Inc.

Eligibility Criteria

This trial is for individuals undergoing primary unilateral total knee arthroplasty (knee replacement surgery) to assess pain relief. Participants must meet certain health criteria, which are not specified here.

Inclusion Criteria

Are you scheduled for just one elective surgery with no other procedures planned at the same time?

Exclusion Criteria

Besides the surgery, do you have another chronic pain condition (like severe arthritis or fibromyalgia) that regularly needs pain meds?

Have you ever had an allergic reaction to Tylenol, Advil, aspirin, or opioid pain medicines?

Have you been treated for drug or alcohol dependence in the last two years, or do you currently use recreational drugs?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ATX101, saline placebo, or bupivacaine during total knee arthroplasty

1 week

In-hospital stay for surgery and initial recovery

Follow-up

Participants are monitored for pain intensity and opioid consumption

2 weeks

Follow-up visits at Day 8 and Day 15

Treatment Details

Interventions

• ATX101
• Bupivacaine Hydrochloride
• Saline Placebo

Trial Overview The study tests the effectiveness and safety of a drug called ATX101 (1,500 mg) compared to a saline placebo and bupivacaine hydrochloride, an established pain reliever. It also measures opioid use post-surgery among participants.

Participant Groups

Group I: ATX101 Experimental Treatment 1 Intervention

Group II: bupivacaine hydrochloride Active Control 1 Intervention

Group III: saline placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Allay Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

310+

Findings from Research

In a study of 60 elective total knee arthroplasty patients, those who received a bupivacaine injection reported lower pain scores and used fewer narcotics in the first 24 hours post-surgery compared to the placebo group.

Although the bupivacaine group had a shorter discharge time from the postanesthesia care unit by 23 minutes, the differences in pain levels and narcotic consumption were not statistically significant when compared to the placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine bolus injection versus placebo for pain management following total knee arthroplasty. Browne, C., Copp, S., Reden, L., et al.[2022]

In a study of 20 patients undergoing abdominal surgery, infiltration of 0.25% bupivacaine significantly reduced postoperative pain scores and narcotic requirements compared to saline placebo, leading to better pain management in the post-anesthesia care unit (PACU).

Patients receiving bupivacaine also had improved oxygen saturation levels and were discharged from the PACU nearly an hour earlier, suggesting that using a long-acting local anesthetic can enhance recovery and potentially reduce pulmonary complications after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of incisional bupivacaine on postoperative narcotic requirements, oxygen saturation and length of stay in the post-anesthesia care unit. Partridge, BL., Stabile, BE.[2019]

In a study involving 50 patients undergoing elective cholecystectomy, the use of 0.25% bupivacaine for wound infiltration did not provide any significant benefits in terms of postoperative pain relief compared to saline.

Both groups experienced similar declines in lung function after surgery, indicating that bupivacaine did not prevent respiratory complications following the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative wound infiltration with bupivacaine in patients undergoing elective cholecystectomy. van Raay, JJ., Roukema, JA., Lenderink, BW.[2019]

Intraoperative infiltration of bupivacaine during posterior spine surgery significantly reduced opioid consumption in the 72 hours post-surgery, indicating its efficacy as a pain relief adjunct.

Patients receiving bupivacaine also reported slightly lower pain scores and had better heart rate control, with no complications or significant increase in surgical time or hospital stay, highlighting its safety and practicality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradermal and Intramuscular Bupivacaine Reduces Opioid Use Following Noninstrumented Spine Surgery. Cleary, DR., Tan, H., Ciacci, J.[2023]

HYR-PB21-LA, a new microparticle suspension of bupivacaine pamoate, demonstrated significantly longer-lasting local anesthesia effects compared to traditional bupivacaine hydrochloride, lasting up to five times longer in animal tests.

In head-to-head comparisons, HYR-PB21-LA showed superior efficacy over liposomal bupivacaine, providing effective pain relief for up to 8 hours versus just 1 hour with the liposomal formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HYR-PB21-LA, a potential extended-release bupivacaine formulation, produces long-lasting local anesthesia in rats and guinea pigs. Peng, J., Liu, C., Liu, J., et al.[2021]

In a randomized trial with 41 patients undergoing elective hysterectomy, preoperative wound infiltration with bupivacaine 0.25% significantly reduced the total amount of postoperative buprenorphine needed compared to a placebo, indicating better pain management.

Patients receiving bupivacaine experienced a delay in the demand for additional analgesics, suggesting that bupivacaine effectively prolongs pain relief after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative wound infiltration with bupivacaine reduces early and late opioid requirement after hysterectomy. Hannibal, K., Galatius, H., Hansen, A., et al.[2019]

A study analyzing 528 reports of paraesthesias linked to local anesthetics found that only articaine and prilocaine showed significant alert signals for causing these sensations, particularly in dental settings.

Articaine had a very high reporting odds ratio (ROR=18.38), indicating a strong association with oral paraesthesia, while prilocaine also showed a notable association (ROR=2.66), suggesting caution when using these anesthetics in dentistry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paraesthesia after local anaesthetics: an analysis of reports to the FDA Adverse Event Reporting System. Piccinni, C., Gissi, DB., Gabusi, A., et al.[2015]

In a study involving 823 patients across various surgical settings, liposome bupivacaine demonstrated a lower incidence of adverse events (62%) compared to bupivacaine HCl (75%) and placebo (43%), indicating better tolerability.

Serious adverse events were less common in the liposome bupivacaine group (2.7%) compared to bupivacaine HCl (5.4%), suggesting that liposome bupivacaine may be a safer option for local analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of liposome bupivacaine, a novel local analgesic formulation. Viscusi, ER., Sinatra, R., Onel, E., et al.[2022]

The bupivacaine implant (XARACOLL) significantly reduced pain intensity in the first 24 hours after abdominoplasty compared to placebo, indicating its efficacy in providing postoperative analgesia.

Patients receiving the bupivacaine implant had a higher percentage of opioid-free patients at 24, 48, and 72 hours post-surgery, suggesting it may help reduce reliance on opioids for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty. Beaton, AC., Solanki, D., Salazar, H., et al.[2023]

HTX-011, an extended-release local anesthetic, effectively reduced postoperative pain and opioid use in bunionectomy patients, with 77% of participants remaining opioid-free during recovery.

The combination of HTX-011 with scheduled ibuprofen and acetaminophen maintained mild pain levels (NRS <4) for 72 hours post-surgery, demonstrating its safety and efficacy as part of a multimodal analgesia regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-Free Recovery from Bunionectomy with HTX-011, a Dual-Acting Local Anesthetic Combining Bupivacaine and Meloxicam, as the Foundation of Non-Opioid Multimodal Analgesia. Pollak, R., Cai, D., Gan, TJ.[2021]

Infiltrating the surgical wound with bupivacaine hydrochloride during elective cholecystectomy significantly improved postoperative lung function, with FEV1 and FVC values at 72% and 78% of preoperative levels, respectively, compared to only 50% in the saline group.

Patients receiving bupivacaine required fewer narcotic doses (6.5) compared to those receiving saline (10.8) through day 3, indicating better pain management and reduced narcotic use without complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of incisional infiltration of bupivacaine hydrochloride upon pulmonary functions, atelectasis and narcotic need following elective cholecystectomy. Patel, JM., Lanzafame, RJ., Williams, JS., et al.[2013]

0.5% bupivacaine hydrochloride offers superior pain relief compared to 2% lidocaine in oral and maxillofacial surgery, indicating its effectiveness as a local anesthetic.

The use of bupivacaine comes with only a minimal increase in cost for the surgeon, making it a cost-effective option for enhanced analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the analgesic efficacy and cost-effective use of long-acting local anesthetics in outpatient third molar surgery. Neal, JA., Welch, TB., Halliday, RW.[2019]

References

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

Bupivacaine bolus injection versus placebo for pain management following total knee arthroplasty. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The effects of incisional bupivacaine on postoperative narcotic requirements, oxygen saturation and length of stay in the post-anesthesia care unit. [2019]

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

Intraoperative wound infiltration with bupivacaine in patients undergoing elective cholecystectomy. [2019]

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

Intradermal and Intramuscular Bupivacaine Reduces Opioid Use Following Noninstrumented Spine Surgery. [2023]

5. England pubmed.ncbi.nlm.nih.gov

HYR-PB21-LA, a potential extended-release bupivacaine formulation, produces long-lasting local anesthesia in rats and guinea pigs. [2021]

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

Preoperative wound infiltration with bupivacaine reduces early and late opioid requirement after hysterectomy. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Paraesthesia after local anaesthetics: an analysis of reports to the FDA Adverse Event Reporting System. [2015]

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

The safety of liposome bupivacaine, a novel local analgesic formulation. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty. [2023]

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

Opioid-Free Recovery from Bunionectomy with HTX-011, a Dual-Acting Local Anesthetic Combining Bupivacaine and Meloxicam, as the Foundation of Non-Opioid Multimodal Analgesia. [2021]

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

The effect of incisional infiltration of bupivacaine hydrochloride upon pulmonary functions, atelectasis and narcotic need following elective cholecystectomy. [2013]

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

Analysis of the analgesic efficacy and cost-effective use of long-acting local anesthetics in outpatient third molar surgery. [2019]