An open-label, single-sequence study to investigate the effects of gastric acid suppression by Rabeprazole on the pharmacokinetics of BMS-986165 in healthy participants

BMS-986165 is a new compound that may eventually be used for the treatment of
autoimmune diseases like lupus, moderate to severe psoriasis, and inflammatory
bowel disease. In autoimmune diseases the immune system does not only react to
foreign substances, as it should, but also to parts of the body. This results
in inflammatory reactions throughout the body (lupus), in the skin (psoriasis),
or in the bowel (inflammatory bowel disease). The study compound blocks an
enzyme (tyrosine kinase 2 [TYK2]) which has a role in the immune response and
should decrease the immune response to parts of the body.

There are indications that the acidity of the stomach influences the uptake of
BMS-986165. To study this, the uptake of the study compound with normal gastric
acidity will be compared with the uptake after the gastric acid production has
been reduced by rabeprazole for several days.

The purpose of this study is to investigate how quickly and to what extent the
new compound BMS-986165 is absorbed and eliminated from the body (this is
called pharmacokinetics) when it is administered to healthy volunteers without
and with rabeprazole, a drug used to reduce the production of stomach acid (a
proton-pump inhibitor). BMS-986165 has been administered to humans before.

It will also be investigated how safe BMS-986165 is and how well it is
tolerated when administered without and with rabeprazole.

This study will be performed in 20 healthy male/female volunteers.

The actual study will consist of 1 period during which the volunteer will stay
in the research center for 13 days (12 nights).

Day 1 is the first day of administration of the study compound. The volunteers
are expected at the research center at 10:00 h in the morning prior to the day
of first administration of the study compound. The volunteers will leave the
research center on Day 12 of the study.

BMS-986165 and rabeprazole will be given as oral tablets with 240 milliliters
(mL) of water.

During the first 4 hours after administration of the study compound the
volunteer will not be allowed to lie down (except when indicated as such by one
of the investigators), as this may influence the uptake of the study compound.

One of the investigators will inspect the hands and mouth after the study
compound intake.

Please refer to the table below to see the planned dose levels for each group.

Day Treatment How often Fasted or Fed*
1 BMS-986165 12 mg once daily fasted
5-8 rabeprazole 20 mg once daily fed
9 BMS-986165 12 mg and rabeprazole 20 mg once daily fasted
10-11 rabeprazole 20 mg once daily fed

BMS-986165 and rabeprazole will be given as oral tablets with 240 milliliters
(mL) of water.

During the first 4 hours after administration of the study compound the
volunteer will not be allowed to lie down (except when indicated as such by one
of the investigators), as this may influence the uptake of the study compound.

One of the investigators will inspect the hands and mouth after the study
compound intake.

Please refer to the table below to see the planned dose levels for each group.

Day Treatment How often Fasted or Fed*
1 BMS-986165 12 mg once daily fasted
5-8 rabeprazole 20 mg once daily fed
9 BMS-986165 12 mg and rabeprazole 20 mg once daily fasted
10-11 rabeprazole 20 mg once daily fed

BMS-986165
BMS-986165 is a compound that is being tested in research studies and is not an
approved medicine to treat any condition.

Overall, approximately 774 participants, across 14 research studies, have
received one dose or multiple doses of the study compound BMS-986165,
comparator treatment, or placebo (a medicine without any active ingredient, a
*fake* medicine). In these studies, most of the side effects were mild or
moderate in intensity. In a few cases, side effects were serious and required
hospitalization. This included 2 side effects in healthy volunteers. One
volunteer, with a history of skin abscesses developed an abscess on the forearm
which required hospital treatment. Another volunteer developed severe
pharyngitis, a swollen face and swollen lymph nodes and trismus (lockjaw) also
requiring hospital treatment. Both volunteers recovered completely.

In the research study of BMS-986165, the dose level will be 12 mg.

The side effects described below are based on unblinded information (ie, the
actual study treatment given is known) about side effects observed in 276
participants who got multiple doses of BMS-986165 alone up to a maximum dose of
12 mg daily.

The following side effects are most frequently observed (in 10% of users or
more):
• Headache

For other (important) side effects, or side effects which may occur based on
the mechanism of action of BMS­986165.

The study compound may also have side effects that are still unknown.

You should immediately contact the responsible doctor if you develop:
- sudden shortness of breath
- problems breathing
- swelling of the eyelids, the face or the lips
- rash or itching (especially when on the whole body)

Rabeprazole
Rabeprazole may also cause side effects. The most important ones (in 1 in 100
people or more) are:
- Infection
- Sleeplessness
- Headache, dizziness
- Cough, sore throat (inflammation of the pharynx), runny nose
- Diarrhea, vomiting, nausea, abdominal pain, constipation, wind (flatulence)
- Non-specific pain, back pain
- Weakness or loss of strength, flu like symptoms.

Possible discomforts due to procedures
Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising.

In total, we will take less than 500 milliliters (mL) of blood from the
volunteer. This amount does not cause any problems in adults.

To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on your arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).