VIVITROL as a Treatment for Cocaine and Alcohol Dependence

This is a Phase II double-blind randomized controlled clinical pilot study. The exploratory
objectives in the proposed study will be examined with a 2-group design to assess the
efficacy of naltrexone extended-release injectable suspension (VIVITROL™) as compared to
placebo. Safety measures will be collected weekly through medical management (MM) by medical
practitioners, including adverse events and concomitant meds. The psychosocial treatment will
be Cognitive Behavioral Coping Skills Therapy (CBT). Subjects will be 80 men and women with
current DSM-IV diagnoses of alcohol dependence and cocaine dependence that will be randomized
to receive either VIVITROL or placebo (40 subjects per group). All subjects will receive
weekly sessions of CBT and MM. The study length for each subject is comprised of 1-3 weeks of
screening, an 8-week double-blind, placebo-controlled trial with MM and CBT (medication
phase), and an end of medication visit.

Primary Exploratory Objectives:

- To compare medication groups' rates of cocaine abstinence, as determined by urine assay
for benzoylecgonine (BE), the primary metabolite of cocaine. This will be cross-checked
against participants' self-reports of cocaine use through Time-Line Follow Back
(TLFB)(Sobell & Sobell, 1992).

- To compare medication groups' rates of abstinence from drinking, and of clinically
significant drinking, as measured by the TLFB.

Secondary Exploratory Objectives:

- To evaluate medication groups' reports of craving for cocaine and alcohol, as measured
by scores on the Penn Alcohol Craving Scale and the Minnesota Cocaine Craving Scale
during the medication treatment phase.

- To compare women's reports of medication tolerance of naltrexone extended-release
injectable suspension versus high dose oral naltrexone that was reported in our recently
published pilot trial of high dose naltrexone for dual cocaine and alcohol dependence
(Pettinati et al., 2008).

Inclusion Criteria

1. Males and females, 18 to 65 years old.

2. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical
Interview for DSM-IV (SCID).

3. Meets DSM-IV criteria for Alcohol Dependence, as determined by the Structured Clinical
Interview for DSM-IV (SCID).

4. Meets the following drinking criteria as measured by the Timeline Followback (TLFB)
(Sobell, 1995)

1. drank within 30 days of intake day,

2. reports a minimum of XX standard alcoholic drinks in a consecutive 30-day period
over the 90-day period prior to starting intake, and

3. has 2 or more days of heavy drinking

5. In the past 30 days prior to consent, used no less than $ of cocaine.

6. Live within a commutable distance of the Treatment Research Center (TRC) at the
Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to
be a distance within the service area of Septa, within an hour drive, or a distance
that both the patient and Principal Investigator (PI) find acceptable.

7. Understands and signs the informed consent.

8. Three consecutive days of abstinence from alcohol, and a Clinical Institute Withdrawal
Scale for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight.

4.2 Exclusion Criteria:

1. Positive urine drug screen and/or current DSM-IV diagnosis of any psychoactive
substance dependence other than cocaine, alcohol, or nicotine dependence, as
determined by the SCID.

2. Concomitant treatment with psychotropic medications, including opioid analgesics.

3. Patients mandated to treatment based upon a legal decision or as a condition of
employment.

4. Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal
ideation, mania or depression requiring antidepressant therapy in the opinion of the
Principal Investigator (PI).

5. Taken any investigational medication within the past 30 days.

6. History within the six months prior to randomization of significant heart disease (an
arrhythmia which required medication, Wolff-Parkinson-White Syndrome, angina pectoris,
documented history of myocardial infarction, heart failure). These are to be reviewed
on a case-by-case basis: EKG 1st degree heart block, sinus tachycardia, left axis
deviation, and nonspecific ST or T wave changes are allowed; liver function tests
[LFTs] <3 x ULN are acceptable).

7. Known hypersensitivity to naltrexone, PLG, carboxymethylcellulose, or any other
components of the diluent.

8. Subjects with a BMI of 40 and above, as determined by the Body Mass Index Table, or
that have distribution of adipose tissue such that they would be at greater risk of
serious injection site reaction, based on clinical judgment. Participants with a BMI
over 30 will have additional screening procedures conducted to determine inclusion in
the study. These procedures include an additional screening measurement of waist-hip
ratio for those participants with a BMI over 30. Males with a waist to hip ratio of
>0.9 and females with a waist to hip ratio of >0.85 will be referred to the
investigator for final decision of study inclusion. If the ratio is <0.9 for men or
<0.85 for women they will be eligible for study inclusion without further action.

9. Patients with any serious illnesses that may require hospitalization during the study.

10. Female subjects who are pregnant or lactating, or female subjects of child-bearing
potential who are not using acceptable methods of birth control. Acceptable methods of
birth control include:

11. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits
that are clinically unacceptable to the Principal Investigator.

12. Current physiological opioid dependence.

13. Experiencing acute opiate withdrawal.

14. Likely to receive scheduled surgery, which may require treatment with opioid
analgesics.