Open-Label Pilot Study of Lisdexamfetamine for Cocaine Dependence

In an eight-week open label outpatient pilot trial, we will evaluate the safety,
tolerability, and potential utility of LDX in the treatment of cocaine dependence. Patients
will receive a flexible-fixed dosing schedule under open-label conditions. Patients will be
titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and
then maintained on the highest tolerated dose for four weeks, followed by a two week run-down
period. All participants will receive medication management counseling and individual therapy
using a structured compliance enhancement manual designed for pharmacotherapy trials in
subjects with substance use disorders.

The primary outcome measures will be 1) the maximum total lisdexamfetamine dose achieved
during the study period defined as the highest amount of medication per day maintained for a
seven day period 2) lisdexamfetamine tolerability as measured by adverse effects reported on
the Systematic Assessment for Treatment and Emergent Events (SAFTEE). Secondary outcome
measures will be 1) cocaine use as recorded by the number of days of use on the Timeline
Follow-Back method (Sobell & Sobell, 1992) and confirmed by urine toxicology, 2) cocaine
craving as measured by the Cocaine Craving Scale (CCS) and Cocaine Craving Questionnaire
(CCQ) and 3) alternate measures of cocaine use, such as the dollar value of cocaine used per
day, as measured by the Timeline Follow-Back method, and the proportion of urine toxicology
samples negative for cocaine.

Inclusion Criteria:

- Individuals must be treatment seeking

- Men and women between the ages of 18-60 who meet DSM-IV criteria for current cocaine
dependence

- Used cocaine at least four days in the past month

- Individuals must be in good general health

- Individuals must be capable of giving informed consent and capable of complying with
study procedures

- Women of child-bearing age must agree to use a method of contraception with proven
efficacy, consisting of one of the following: 1) Any form of hormonal contraception;
2) Intra-uterine device; 3) Sterilization; 4) Double-barrier contraception which is a
combination of two of the following: condoms, spermicide, diaphragm. Pregnancy tests
will be performed monthly and if a woman becomes pregnant, the study medication will
be discontinued.

Exclusion Criteria:

- Individuals who meet DSM-IV-TR criteria for bipolar disorder, schizophrenia, any
psychotic disorder other than transient psychosis due to drug abuse, or current major
depressive disorder

- Individuals with any other current Axis I psychiatric disorder as defined by DSM-IV-TR
that in the investigator's judgment are unstable, or would be disrupted by study
medication, or are likely to require pharmacotherapy during the study period

- Individuals physiologically dependent on any other drugs (excluding nicotine or
cannabis) which require medical intervention

- Individuals with current psychostimulant abuse or dependence (other than cocaine
dependence)

- Individuals with current suicidal risk

- Individuals with coronary vascular disease as indicated by history or suspected by
abnormal ECG or history of cardiac symptoms

- Unstable physical disorders which might make participation hazardous such as
uncontrolled hypertension (SBP > 140, DBP> 90, or HR > 100 when sitting quietly),
acute hepatitis (patients with chronic mildly elevated transaminases < 1.5x upper
limit of normal are acceptable), or uncontrolled diabetes

- Individuals with a history of seizures, hyperthyroidism and/or glaucoma

- Individuals with a family history of sudden cardiac death

- History of allergic reaction to study medication

- Women who are pregnant or nursing

- Currently being prescribed psychotropic medication by another physician (other than
sleep medication)

- Individuals who are legally mandated (e.g., to avoid incarceration) to participate in
substance abuse treatment program