Purpose of the NAVIGATOR-2 Study

The purpose of the NAVIGATOR-2 Study is to evaluate the safety and effectiveness of an investigational drug in individuals with painful lumbosacral radiculopathy (PLSR), commonly known as sciatica. The word “investigational” means this medication is not yet approved for use by the Food and Drug Administration (FDA) in the United States or other regulatory agencies in Canada, Europe, or elsewhere.

The investigational drug, called VX-548, is designed to target a sodium channel in the body called NaV1.8. Researchers are evaluating if targeting and inhibiting this sodium channel treats pain from PLSR. Participants in this study will be selected at random to receive either the investigational drug or a placebo (a substance that looks just like the investigational drug but does not contain any active medication). The assigned study treatment will be taken as three oral tablets in the morning every day. Neither the participant nor the study doctor will know if the participant has been assigned to the investigational drug or the placebo, but in case of emergency, the study doctor can quickly find out.

Who May Qualify

Eligible participants must:

  • Be between the ages of 18 and 70 (inclusive)
  • Have had symptoms of sciatica for more than three months
  • Have pain in one leg, with leg pain worse than back pain

There are additional eligibility requirements, which the study doctor can explain to you.

Study Participation

Study participation lasts approximately 19 weeks and consists of the following periods:


This period lasts approximately four weeks and consists of two visits. The purpose of this period is to make sure the potential participant is eligible to participate in the study.


This period lasts one week. During each morning of this period, participants will be required to report their average daily leg pain and how their pain may have interfered with their sleep. They will also follow the treatment restriction guidelines they receive from the study doctor.

Study Treatment

This period lasts approximately 12 weeks and consists of five visits. In this period, participants will receive either the investigational drug or the placebo, and the study team will monitor the participant’s health while they are taking the assigned study treatment.


Approximately two weeks after completing the study treatment period, participants will have a final follow-up visit to check their health.

Throughout the study, the study doctor may perform a number of tests and procedures, including but not limited to:

  • Recording medical history

  • Conducting physical exams

  • Measuring vital signs

  • Conducting pregnancy tests (if applicable)

  • Collecting blood and urine samples

Compensation for study-related time as well as reimbursement for travel may be available.

See if you may qualify