Modafinil Treatment for Cocaine-Dependent Individuals

Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled
conditions. Due to its stimulant-like properties, modafinil is also likely to relieve severe
cocaine withdrawal symptoms. In turn, this may lead to better clinical outcomes. The purpose
of this study is to determine whether modafinil improves abstinence during early recovery
from cocaine dependence.

This 6-month, double-blind, placebo-controlled trial will enroll 210 participants with
current DSM-IV diagnoses of cocaine dependence. Treatment will occur for 8 weeks.
Participants will be randomly assigned to receive a single morning dose of low-dose modafinil
(200 mg/day), high-dose modafinil (400 mg/day), or matching placebo tablets. In addition,
each week participants will receive manual-guided cognitive behavioral therapy at the
Treatment Research Center. At the end of the 8-week treatment period, modafinil or placebo
will be abruptly discontinued. One week following, an end of medication evaluation will
occur. In addition to this, two follow-up evaluations will take place 3 and 5 months after
initial randomization. Efforts will be made to continue evaluation of subjects who decide to
discontinue the modafinil treatment. Urine benzoylecgonine levels will be used to measure
cocaine abstinence. Craving, withdrawal, retention, and adverse events will also be
evaluated.

Inclusion Criteria:

- Male or female, aged 18 - 60 years;

- Current DSM-IV diagnosis of cocaine dependence

- Using at least $200 worth of cocaine within the past 30 days and having positive urine
toxicology (BE) during screening;

- Able to provide written informed consent and to comply with all study procedures;

- Women must be surgically sterile, at least two years postmenopausal, or if of
childbearing potential be using a medically accepted method of birth control and agree
to continue use of this method for at least 30 days after the last dose of study drug
(i.e. barrier method with spermicide, steroidal contraceptive [oral and implanted,
including Depo-Provera contraceptives must be used in conjunction with a barrier
method], or intrauterine device [IUD])

Exclusion Criteria:

- Currently dependent on any substance other than cocaine or nicotine

- Neurological or psychiatric disorders, such as psychosis, bipolar illness, organic
brain disease, dementia, or any diseases that require psychotropic medications

- Serious medical illnesses, including but not limited to; uncontrolled hypertension,
significant heart disease (including a history of myocardial infarction, angina,
mitral valve prolapse, left ventricular hypertrophy, palpitations, and arrhythmia),
hepatic disease, renal disease, or any serious, potentially life-threatening or
progressive medical illness that may compromise patient safety or study conduct;

- Received a drug with known potential for toxicity to a major organ system within the
month prior to entering treatment including but not limited to; chemotherapeutic
agents for neoplastic disease (i.e. methotrexate, vincristine, vinblastine,
fluorouracil), agents used for parasitic infections, isoniazid, chlorambucil,
dactinomycin, chloramphenicol, immunosuppressive and cytotoxic agents (i.e.
cyclosporine, tacrolimus), indomethacin, protease inhibitors, amphotericin B,
cephalosporins, aminoglycosides, interferon, and sulfonamides;

- Clinically significant abnormal laboratory values

- Has any disease of the gastrointestinal system, liver, or kidneys which could result
in altered metabolism or excretion of the study medication (history of major
gastrointestinal tract surgery, gastrectomy, gastrostomy, bowel resection, etc.) or
history of chronic gastrointestinal disorders (ulcerative colitis, regional enteritis,
or gastrointestinal bleeding);

- Known hypersensitivity or allergy to modafinil or receiving chronic therapy with any
medication that could interact adversely with one of the medications under study,
including propranolol, phenytoin, warfarin and diazepam;

- Currently taking any medication that could interact adversely with one of the
medications under study, including propranolol, phenytoin, warfarin and diazepam

- Took monoamine oxidase inhibitors (MAOI) within 30 days prior to randomization;

- Taking or has taken an investigational drug within 60 days prior to enrollment

- If female and of child-bearing capacity, tests positive on a urine pregnancy test, is
lactating, has had three or more days of amenorrhea beyond expected menses at the time
of the first dose of study medication, is contemplating pregnancy in the next 6
months, or is not using an effective contraceptive method;

- Received therapy with any opiate-substitute (methadone, LAAM, buprenorphine) within 60
days of study enrollment.