VX-993 for Pain

Overseen By Medical Information

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Febrile illness, Drug absorption issues, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

8 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug 14C-VX-993 for pain management?

The research highlights the importance of using sensory tests and pain biomarkers to confirm how well new pain drugs work in humans, which can help ensure that drugs like 14C-VX-993 effectively target pain pathways. ^{1 2 3 4 5}

Is VX-993 safe for humans?

The study on tetrodotoxin (TTX), a similar compound, showed it is safe and well-tolerated in healthy adults, with no serious heart-related side effects and only mild common side effects like headache and nausea. ^{6 7 8 9 10}

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

VX-993 is unique because it involves the use of 14C-VX-993, which may target specific pathways involved in pain, potentially offering a novel mechanism of action compared to existing treatments. While the exact details of VX-993 are not provided, similar treatments like VX-128 focus on inhibiting specific sodium channels involved in pain signaling, which could suggest a targeted approach for pain relief. ^{7 11 12 13 14}

What is the purpose of this trial?

The purpose of the study is to evaluate the routes and rate of elimination and recovery of total radioactivity (TRA) and characterize the Pharmacokinetic (PK) of VX-993 after a single oral dose of 14C-VX-993

Eligibility Criteria

This trial is for individuals over 50 kg with a BMI of 18.0 to 32.0 who have at least one regular bowel movement daily. It's not specified who can't join, but typically those with health conditions affecting drug processing or conflicting medications would be excluded.

Inclusion Criteria

I have at least one bowel movement every day.

My BMI is between 18.0 and 32.0.

I weigh more than 50 kg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of 14C-VX-993 after an overnight fast

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• 14C-VX-993

Trial Overview The study is testing how the body processes and eliminates a single oral dose of a pain medication called 14C-VX-993 by tracking its radioactivity in the body and understanding its pharmacokinetics (how the drug moves inside the body).

Participant Groups

Group I: 14C VX-993 Experimental Treatment 1 Intervention

Participants will receive a single oral dose of 14C-VX-993 after an overnight fast of at least 8 hours.

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

Pharmacogenomics (PGx) testing can enhance pain management by allowing for more precise selection and dosing of analgesics based on individual genetic responses, which is crucial given the variability in how patients respond to pain medications.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides guidelines that can help healthcare providers apply PGx data in clinical practice, particularly for patients with cancer, to improve the efficacy and safety of pain pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating pharmacogenomics into precision pain management. Bates, J., Fudin, J., Patel, JN.[2022]

QX-314, a derivative of lidocaine, selectively inhibits nociceptors expressing TRPV1 channels but may cause central nervous system (CNS) toxicities that are about twice as potent as lidocaine.

In newborn rat brainstem-spinal cord preparations, QX-314 decreased respiratory rhythm generation, indicating potential risks for respiratory function when used systemically.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats. Takahashi, K., Hayakawa, C., Onimaru, H.[2016]

VX-128, a selective Nav 1.8 inhibitor, was found to be well-tolerated in single doses up to 300 mg, but showed a higher incidence of adverse effects compared to placebo, with 41.7% of subjects experiencing side effects.

In a multiple-ascending dose study, skin rashes and one serious case of angioedema were reported, leading to early termination of the study, although VX-128 demonstrated a dose-dependent trend in increasing pain tolerance in certain pain tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, randomized, double-blind, placebo-controlled, single- and multiple dose escalation study evaluating the safety, pharmacokinetics and pharmacodynamics of VX-128, a highly selective Nav 1.8 inhibitor, in healthy adults. Hijma, HJ., van Brummelen, EMJ., Siebenga, PS., et al.[2022]

References

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

Use of sensory methods for detecting target engagement in clinical trials of new analgesics. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Integrating pharmacogenomics into precision pain management. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Assessing clinically meaningful change following a programme for managing chronic pain. [2008]

4. Thailand pubmed.ncbi.nlm.nih.gov

Pain reduction of a pain management regimen in orthopedic patients at Lamphun Hospital. [2019]

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

Make a CHANGE: optimising communication and pain management decisions. [2011]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Concentration-QTc Analysis of Tetrodotoxin: A Randomized, Dose Escalation Study in Healthy Adults. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Spinal sensitization mechanism in vincristine-induced hyperalgesia in mice. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats. [2016]

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

A Phase I, Randomized, Double-Blind, Laser-Evoked Potential Study to Evaluate the Analgesic/Antihyperalgesic Effect of ASP9226, a State-Dependent N-Type Voltage-Gated Calcium Channel Inhibitor, in Healthy Male Subjects. [2019]

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

An unbiased and efficient assessment of excitability of sensory neurons for analgesic drug discovery. [2022]

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

A phase I, randomized, double-blind, placebo-controlled, single- and multiple dose escalation study evaluating the safety, pharmacokinetics and pharmacodynamics of VX-128, a highly selective Nav 1.8 inhibitor, in healthy adults. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

New index of pain triggered by spinal activation of voltage-dependent sodium channels. [2021]

13. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Pharmacological Inhibition of Voltage-gated Ca(2+) Channels for Chronic Pain Relief. [2022]

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

Limited efficacy of α-conopeptides, Vc1.1 and RgIA, to inhibit sensory neuron CaV current. [2022]