VX-993 for Acute Pain

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Vertex Pharmaceuticals Incorporated

Must not be taking: Anti-arrhythmia treatments

Disqualifiers: Foot surgery, Cardiac dysrhythmias, HIV, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of VX-993 in treating acute pain after a bunionectomy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How does the drug VX-993 differ from other treatments for acute pain?

VX-993, also known as resiniferatoxin (RTX), is unique because it targets specific nerve fibers responsible for pain without affecting other sensory or motor functions. It provides long-lasting pain relief by blocking pain conduction in these fibers, which is different from traditional pain medications that often affect broader nerve functions. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals scheduled to have a bunionectomy (a type of foot surgery) using regional anesthesia. Participants must be able to follow instructions and adhere to pain management guidelines before and after the procedure.

Inclusion Criteria

I followed all pain management instructions after my bunion surgery.

I am scheduled for a bunion surgery on one foot with a specific technique.

I am mentally alert and can follow instructions.

Exclusion Criteria

I have had surgery on my foot before.

I have had heart rhythm problems treated in the last 2 years.

I do not have an active HIV, hepatitis B, or hepatitis C infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized doses of VX-993, HB/APAP, or placebo to evaluate efficacy and safety for acute pain after bunionectomy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VX-993 (Other)

Trial Overview The study tests VX-993's effectiveness in managing acute pain post-bunionectomy, comparing it with HB/APAP (likely a standard painkiller) and placebos that match each drug. It also assesses safety, tolerability, and how the body processes VX-993.

Participant Groups

Group I: VX-993 Experimental Treatment 2 Interventions

Participants will be randomized to receive different dose levels of VX-993.

Group II: Hydrocodone bitartrate/acetaminophen (HB/APAP) Active Control 2 Interventions

Participants will be randomized to receive HB/APAP.

Group III: Placebo Placebo Group 2 Interventions

Participants will be randomized to receive placebos matched to VX-993 and HB/APAP.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Findings from Research

In a rat model, perineural administration of resiniferatoxin (RTX) completely prevented hyperalgesia (increased sensitivity to pain) following an incision, demonstrating its efficacy in managing postoperative pain.

RTX effectively blocked pain responses without affecting nonpainful sensations or motor functions, indicating a potential for safe pain management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. Kissin, I., Davison, N., Bradley, EL.[2021]

The increasing-temperature hot plate (ITHP) method effectively measures the noxious heat threshold in unrestrained rats, showing consistent results over time, which is important for evaluating pain responses.

Morphine, diclofenac, and paracetamol were found to significantly elevate the heat threshold, indicating their analgesic efficacy, while the VR1 receptor agonist resiniferatoxin (RTX) induced a notable drop in heat threshold, demonstrating its potential to model heat allodynia and sensitivity to pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics. Almási, R., Pethö, G., Bölcskei, K., et al.[2018]

This rapid review analyzed 15 studies involving 1043 patients with monkeypox virus (MPXV) to summarize pain management strategies, highlighting that severe pain is a common reason for medical attention and hospital admission.

Proposed treatments for managing pain associated with MPXV include acetaminophen, ibuprofen, opioids, and topical options like lidocaine gel, indicating a need for clearer guidelines to optimize pain management and reduce patient morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain Associated With Monkeypox Virus: A Rapid Review. Hallo-Carrasco, A., Hunt, CL., Prusinski, CC., et al.[2023]

Vanilloid agonists like resiniferatoxin (RTX) provide effective conduction analgesia by selectively targeting pain-related nerve fibers (C- and ADelta-fibers) without affecting other sensory or motor functions, making them a promising alternative to traditional local anesthetics.

In rat studies, RTX demonstrated long-lasting pain relief with minimal nerve damage compared to lidocaine, suggesting a wider therapeutic window and potential for clinical use, although initial pain from RTX application requires a local anesthetic to mitigate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vanilloid-induced conduction analgesia: selective, dose-dependent, long-lasting, with a low level of potential neurotoxicity. Kissin, I.[2022]

In a study involving C57BL6 male mice with chronic inflammatory arthritis induced by Complete Freund's Adjuvant, intra-articular injections of capsaicin (CAP) and resiniferatoxin (RTX) significantly improved evoked pain scores (EPS), indicating a reduction in pain perception.

However, while CAP and RTX improved EPS, they did not enhance automated dynamic weight bearing (ADWB) measures, suggesting that these treatments may alleviate pain without affecting the overall weight distribution on the affected limb.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Treatment with Resiniferatoxin and Capsaicin on Dynamic Weight Bearing Measures and Evoked Pain Responses in a Chronic Inflammatory Arthritis Murine Model. Bert, J., Mahowald, ML., Frizelle, S., et al.[2019]

References

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

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. [2021]

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

Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics. [2018]

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

Pain Associated With Monkeypox Virus: A Rapid Review. [2023]

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

Vanilloid-induced conduction analgesia: selective, dose-dependent, long-lasting, with a low level of potential neurotoxicity. [2022]

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

The Effect of Treatment with Resiniferatoxin and Capsaicin on Dynamic Weight Bearing Measures and Evoked Pain Responses in a Chronic Inflammatory Arthritis Murine Model. [2019]