The Role of NaV1.8 in Human Pain Models

NCT07511400 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: EK1933/2025
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to understand how NaV1.8, a specific type of sodium channel found in peripheral nerves, contributes to different types of pain in humans. To address this, suzetrigine, a highly selective blocker of the NaV1.8 channel, is used. While current pain medications often have side effects that limit their use, NaV1.8 is a promising target for new, non-opioid pain treatments because it is primarily located in the nerves that send pain signals to the brain. This study is a randomised, placebo-controlled double-blind crossover microdosing trial. This means that very small, safe amounts of the drug are injected directly into the skin of healthy volunteers to observe its effects locally. This approach ensures the drug works only at the injection site with negligible exposure to the rest of the body. Healthy volunteers will undergo six different types of brief, controlled pain tests to see which ones are reduced by blocking NaV1.8. These tests are as follows:

• Electrical stimulation: Brief electrical pulses delivered onto the skin.
• Mechanical stimulation: A standardised "pin-prick" stimulation of the skin.
• Chemical stimulation: An injection of fluid containing capsaicin (the active component of chilli peppers) superficially into the skin.
• Heat stimulation: An injection of hot fluid superficially into the skin.
• Cold stimulation: An injection of cold fluid superficially into the skin.
• Acid stimulation: An injection of acidic fluid superficially into the skin. By comparing the effects of suzetrigine against a placebo and a standard local anaesthetic (lidocaine), the study will help determine which specific pain modalities critically depend on NaV1.8.

Conditions

Pain; Acute Pain; Healthy Volunteer Study

Keywords

Suzetrigine; VX-548; NaV1.8 Inhibitor; Sodium Channel Blocker; Selective NaV1.8 Antagonist; Microdosing; Intracutaneous injection; Experimental Pain Models; Human Pain Models; Capsaicin-induced pain; Thermal pain (Heat and Cold); Mechanical pain; Electrical stimulation; Acid-induced pain; Nociception

Outcome Measures

Primary Outcomes (6)

• Pain Intensity: Electrical stimulation

  Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The average of all provided pain ratings divided by the number of delivered stimuli (maximum of 23 stimuli). If a subject stops the test upon reaching a rating of 30, the average is calculated based on the actual number of stimuli delivered.

  1.5 minutes post-injection.

• Geometric Mean Pain Intensity: Mechanical stimulation

  Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The geometric mean of the pain ratings recorded from three standardized mechanical stimuli (3.6N force).

  1.5 minutes post-injection.

• Area Under the Curve (AUC): Capsaicin injection

  Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds, starting from the time of injection until a consecutive rating of 0 is maintained for 30 seconds.

  From injection until 0 pain for 30 seconds.

• Area Under the Curve (AUC): Acid injection

  Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds during the pH decrease from 7.2 to 5.4.

  110 seconds

• Area Under the Curve (AUC): Heat injection

  Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds during the temperature increase from 23°C to 52°C.

  150 seconds

• Area Under the Curve (AUC): Cold injection

  Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds during the temperature decrease from 23°C to 4°C.

  150 seconds

Study Arms (3)

Suzetrigine

EXPERIMENTAL

Participants receive intracutaneous injections of suzetrigine at a concentration of 1 µM before or during experimental pain induction across six different modalities (electrical, mechanical, capsaicin, acid, heat, and cold).

Drug: Suzetrigine

Lidocaine

ACTIVE COMPARATOR

Participants receive intracutaneous injections of lidocaine (positive control) at a concentration of 2 mM before or during experimental pain induction across three out of six different modalities (electrical, mechanical, capsaicin).

Drug: Lidocaine (drug)

Control solution

PLACEBO COMPARATOR

Participants receive intracutaneous injections of control solution (negative control) before or during experimental pain induction across six different modalities (electrical, mechanical, capsaicin, heat, and cold).

Drug: Control Solution

Interventions

Suzetrigine DRUG

A selective NaV1.8 inhibitor. It is administered at a concentration of 1 µM via intracutaneous injection at the site of pain induction. The total dose per subject is 1.53 µg.

Suzetrigine

Lidocaine (drug) DRUG

A non-selective NaV inhibitor. It is administered at a concentration of 2 mM via intracutaneous injection at the site of pain induction. The total dose per subject is 120 µg.

Lidocaine

Control Solution DRUG

A control solution mimicking extracellular fluid. It is administered via intracutaneous injection at the site of pain induction.

Control solution

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 70 years

You may not qualify if:

• Participant of another study, ongoing or within the last 4 weeks
• Medication intake (except contraception) or drug abuse
• Female subjects: Positive pregnancy test or breastfeeding
• Verified body temperature above 38°C
• Known allergic diseases, in particular asthmatic disorders
• Limited accessibility of forearms (e.g. orthopedic cast)
• Sensory deficit, skin disease or hematoma at the forarms

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, State of Vienna, 1090, Austria

RECRUITING

MeSH Terms

Conditions

Pain; Acute Pain; Common Cold

Interventions

Lidocaine; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Michael J.M. Fischer, Professor

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Felix J. Resch, PhD

CONTACT

+43 1 40160 31419; felix.resch@meduniwien.ac.at

Michael J.M. Fischer, Professor

CONTACT

+43 1 40160 31410; michael.jm.fischer@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2026
• First Posted: April 6, 2026
• Study Start: April 21, 2026
• Primary Completion (Estimated): October 12, 2026
• Study Completion (Estimated): October 12, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: IPD will be made available at the time of publication of the primary results article, as a supplementary file.
• Access Criteria: All individuals who have access to the published article will be able to access the individual participant data (IPD) and supporting information as supplementary material. No special request or data use agreement is required.

Locations

AU (1)