A phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study evaluating safety and pharmacokinetics of VX-150 including an assessment of the effect of food on the pharmacokinetics of VX-150 in healthy adult subjects.

VX 150 (also called study drug) is a new investigational drug. Investigational
means the study drug is not approved for use and is still being tested for
safety and effectiveness. This study drug may eventually be used for the
treatment of pain. VX 150 is a blocker of sodium (Na) channels, specifically
the NaV1.8 channel. Sodium channels are channels present in the outer layer of
cells, which allow sodium ions to enter the cell in certain circumstances. The
NaV1.8 channel is primarily present in neurons that sense pain and it plays an
important role in pain signaling. This is the first time that this study drug
is being given to humans.

The study will be performed in 2 parts, Parts A and B.
The purpose of Part A of the study is to investigate the safety of VX 150 and
to what extent a single dose of VX 150 is tolerated. It will also be
investigated how quickly and to what extent a single dose of VX 150 is absorbed
and eliminated from the body (this is called pharmacokinetics). In addition,
the effect of food on the pharmacokinetic properties of VX 150 will be
investigated.
The purpose of Part B of the study is to investigate the safety of VX 150 and
to what extent multiple doses of VX 150 are tolerated, and how quickly and to
what extent multiple doses of VX 150 are absorbed and eliminated from the body.

For Groups 1, 2, 3, 5, and 6 the actual study will consist of 1 period during
which the volunteers will stay in the clinical research center in Groningen for
6 days (5 nights). If they participate in Group 4/7 they will stay in the
clinical research center in Groningen for 1 period during which they will stay
in the clinical research center in Groningen for 16 days (15 nights).

Groups 1, 2, 3, 5, and 6
During the study, the volunteers will receive VX 150 or placebo as an oral
solution with 240 milliliters of tap water. Immediately before and after study
drug dosing they will be allowed to use a taste masking solution to mask the
taste of the study drug. They will receive the study drug after an overnight
fast (at least 8 hours no meal). For all groups it is applicable that on Day 1
fasting will continue until 4 hours after study drug administration. Then they
will receive a lunch. During fasting and after study drug administration they
are allowed to drink water with the exception of 2 hours prior to dosing until
2 hours after dosing.

Group 4/7
On Day 1 the volunteers will receive VX 150 or placebo as an oral solution with
240 milliliters of tap water after an overnight fast (at least 8 hours no
meal). Immediately before and after study drug dosing they will be allowed to
use a taste masking solution to mask the taste of the study drug.
On Day 6 and Day 11 they will receive VX 150 as a tablet with 240 milliliters
of tap water. After intake of the tablet, one of the investigators will inspect
the hands and mouth. On Day 6 they will receive VX 150 after an overnight fast
(at least 8 hours no meal) and on Day 11 they will receive the study drug 30
minutes after a breakfast. During fasting and after study drug administration
the volunteers are allowed to drink water with the exception of 2 hours prior
to dosing until 2 hours after dosing.

Group
1: 1 x 25 mg VX 150 or placebo, once
2: 1 x X mg VX 150 or placebo, once
3: 1 x X mg VX 150 or placebo, once
4/7: 1 x X mg VX 150 or placebo en 3 x X mg VX 150 once
5: 1 x X mg VX 150 or placebo, once
6: 1 x X mg VX 150 or placebo, once

All potential drugs cause adverse events; the extent to which this occurs
differs. As VX 150 will be administered to humans for the first time in this
study adverse effects of VX 150 in humans have not been reported to date.
However, VX 150 has been studied in laboratory animals (rats and monkeys) that
have not demonstrated any harmful side effects or toxicities at any tested dose
level. Decreased body weight and lower food consumption were observed in rats
exposed to high doses of the study drug.

Procedures: Pain, light bleeding, hemeatoma and possible an infection.