Modulation of Arachidonic Acid Metabolism by Chemopreventive Agents in Smokers

The Study Drugs:

Zileuton is designed to decrease swelling, tightening, and mucus in the airways.

Celecoxib is designed to decrease inflammation.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the roll of dice) to 1 of 2 groups:

- Group 1 will take zileuton alone.

- Group 2 will take zileuton and celecoxib.

You will have a 3 out of 4 chance of being placed in Group 1, and a 1 out of 4 chance of
being placed in Group 2.

Study Drug Administration:

You will take zileuton by mouth, 2 tablets each time, twice a day for up to 7 days.
Zileuton should be taken within 1 hour after your morning and evening meals. Swallow the
tablets whole, without crushing or breaking them.

If you are in Group 2, you will also take 1 capsule of celecoxib by mouth, twice a day for
up to 7 days. You will take celecoxib at the same time as zileuton.

If you forget to take the morning dose and you remember before the evening dose that same
day, take the missed dose as soon as you remember it. However, if you do not remember until
the next day, skip the missed dose and continue your regular dosing schedule. Do not take
more than 2 doses of each drug in 1 day, and do not take double doses to make up for a
missed dose.

You will fill out a pill diary to help you keep track of the doses. Every day, you will
write down the times you take the study drug(s). If you miss a dose, you should also write
that down in the pill diary.

Baseline Visit:

On Day 1 (the baseline visit), the following tests and procedures will be performed:

- Your medical and surgical history will be recorded.

- You will have a physical exam.

- You will be asked about any drugs you may be taking.

- Urine will be collected to test for certain chemicals in the body that may be linked
with a risk for smoking-related lung disease.

Phone Call:

On the day before your last dose of the study drug(s), the study staff will call and remind
you that you will have an end-of-study visit the next day. You will be reminded to keep
taking the study drugs on schedule, including the next morning.

End-of-Study Visit:

On the day of your end-of-study visit, you should bring the pill diary to the clinic so the
research staff can review it. You should also bring the empty study drug bottle(s). The
following tests and procedures will be performed:

- You will be asked about any drugs you may be taking.

- Urine will be collected to repeat the test for certain chemicals.

- Blood (about 2 teaspoons) will be drawn to check the level of zileuton in your blood.

Length of Study Participation:

You may continue taking the study drug(s) for up to 7 days. You will be taken off the study
drug(s) early if intolerable side effects occur or if the study doctor thinks it is in your
best interest.

You can decide to stop your study participation at any time. Tell the study staff or doctor
if you are thinking about stopping or decide to stop. He or she will tell you how to stop
safely. You may be asked if researchers can still use your medical information. You can
also decide that you do not want researchers to use your information.

Other Instructions:

You should talk to your study doctor about any side effects you may have during the study.

Be sure to tell the study doctor or staff about any drugs you may be taking, including
prescription drugs, over-the-counter drugs, vitamins, and herbal supplements. Other drugs
may not mix well with the study drugs.

You may be asked to avoid donating blood while taking a study drug and for 1 month after you
stop taking a study drug. The study staff will discuss this with you if it applies.

This is an investigational study. Giving zileuton and celecoxib to smokers is
investigational. Both drugs are commercially available and FDA approved for other uses.
Zileuton is FDA approved to treat asthma. Celecoxib is FDA approved to treat arthritis and
a rare condition that can cause colon cancer.

About 80 eligible participants will take part in this research study.