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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new pain relief treatment, ATX101, for individuals undergoing knee replacement surgery due to arthritis-related knee pain. The study compares ATX101 to a saltwater placebo and an existing pain medication, bupivacaine (a local anesthetic), to evaluate how effectively each option reduces pain and the need for opioids after surgery. It is suitable for those planning knee replacement surgery who have not had major knee surgeries recently and can adhere to the study's requirements. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to the development of potentially effective pain relief options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that ATX101 was well tolerated, with safety similar to bupivacaine. Most reported side effects were not severe, suggesting ATX101 could be a safe option for managing post-surgical pain.

Research has shown that bupivacaine is generally safe and well-tolerated, commonly used in surgeries for pain management. Some studies found its side effects were not serious, especially when combined with other drugs. Both treatments in this trial, ATX101 and bupivacaine, have demonstrated promising safety records in past research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for postoperative pain, which often include opioids and non-opioid options like bupivacaine, ATX101 is unique because it targets pain through a different mechanism. Researchers are excited about ATX101 because it offers a novel approach by potentially modulating specific pain pathways, which could lead to effective pain relief with fewer side effects. This distinct action may provide a safer alternative to traditional pain management methods, addressing the ongoing need for more effective and less addictive postoperative pain treatments.

What evidence suggests that this trial's treatments could be effective for postoperative pain?

Research has shown that ATX101, one of the treatments in this trial, can help relieve pain after knee replacement surgery. Studies have found that it significantly reduces pain for up to four weeks post-surgery, allowing patients to use fewer opioids, which are strong painkillers, for pain management. The FDA recognized ATX101 for its promising results in reducing post-surgical pain. In this trial, researchers are comparing ATX101 to bupivacaine hydrochloride, a well-known local anesthetic often used for post-surgical pain management. ATX101's longer-lasting relief could offer a significant improvement over bupivacaine. ^{1 2 3 6 7}

Who Is on the Research Team?

David Hewitt, MD

Principal Investigator

Allay Therapeutics, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. allaytx.com allaytx.com/allay-therapeutics-phase-2b-clinical-study-supports-ability-of-atx101-to-deliver-four-weeks-of-sustained-post-surgical-pain-relief/

Allay Therapeutics' Phase 2B Clinical Study Supports ... ATX101 achieved sustained post-surgical pain relief for up to four weeks for patients following total knee arthroplasty (replacement, or TKA surgery)

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/allay-pain-relief-trial/

Allay's ATX101 offers post-surgical pain relief in Phase IIB ... Patients treated with ATX101 experienced clinically meaningful reductions in pain for up to 30 days post-surgery.

3. brandoncapital.vc brandoncapital.vc/2025/02/19/allay-therapeutics-announces-first-patients-dosed-in-pivotal-phase-2b-registrationtrial-of-atx101-for-post-surgical-pain-management-after-knee-replacement-surgery/

Allay Therapeutics Announces First Patients Dosed in ... ATX101 is designed to provide extended pain relief after surgery, reducing the need for opioids and improving patient recovery; Phase 2b ...

4. synapse.patsnap.com synapse.patsnap.com/article/phase-2b-study-affirms-atx101s-four-week-post-op-pain-relief-efficacy

Phase 2B Study Affirms ATX101's Four-Week Post-Op Pain ... Despite the study's modest size, it showed significant improvements in pain reduction and a reduced need for supplementary opioids. The data ...

5. pharmexec.com pharmexec.com/view/fda-grants-breakthrough-therapy-designation-allay-therapy-post-surgical-pain-total-knee-arthroplasty

FDA Grants Breakthrough Therapy Designation to Allay's ... The breakthrough designation is based on Phase II clinical trial data, which demonstrated that ATX101 provides sustained pain relief for up ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05260008

Study Assessing Pain Relief After Replacement of the Knee This is a Phase 2B randomized, double blind, active controlled, multi-center clinical trial to evaluate the safety and efficacy of ATX-101 in participants ...

7. ryortho.com ryortho.com/2024/05/phase-2b-study-data-for-4-week-tka-analgesic/

Phase 2B Study Data for 4-Week TKA Analgesic “The results from the 112-patient Part A study against bupivacaine standard of care showed rapid and durable pain relief out through 30 days, ...