Safety and Efficacy of Probuphine in the Treatment of Opioid Dependence

Inclusion Criteria:

- Voluntarily provide written informed consent prior to the conduct of any study related
procedures

- Male or female, 18-65 years of age

- Meet DSM-IV criteria for current opioid dependence

- Females of childbearing potential and fertile males must use a reliable means of
contraception

Exclusion Criteria:

- Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS)

- Presence of aspartate aminotransferase (AST) levels ≥ 3 X upper limit of normal and/or
alanine aminotransferase (ALT) levels ≥ 3 X upper limit of normal and/or total
bilirubin ≥ 1.5 X upper limit of normal and/or creatinine ≥ 1.5 X upper limit of
normal

- Received treatment for opioid dependence (e.g., methadone, BPN), within the previous
90 days

- Current diagnosis of chronic pain requiring opioids for treatment

- Candidates for only short term opioid treatment or opioid detoxification therapy

- Pregnant or lactating females

- Previous hypersensitivity or allergy to BPN- or EVA-containing substances or naloxone

- Current use of agents metabolized through CYP 3A4 such as azole antifungals (e.g.,
ketoconazole), macrolide antibiotics (e.g., erythromycin), and protease inhibitors
(e.g., ritonavir, indinavir, and saquinavir)

- Current anti-coagulant therapy (such as warfarin) or an INR > 1.2

- Meet DSM-IV criteria for current dependence on any other psychoactive substances other
than opioids or nicotine (e.g., alcohol, sedatives)

- Current use of benzodiazepines other than physician prescribed use

- Significant medical or psychiatric symptoms or dementia which in the opinion of the
Investigators would preclude compliance with the protocol, patient safety, adequate
cooperation in the study, or obtaining informed consent

- Concurrent medical conditions (such as severe respiratory insufficiency) that may
prevent the patient from safely participating in study; and/or any pending legal
action that could prohibit participation and/or compliance in study

- Participated in a clinical study within the previous 8 weeks