Study of Probuphine in Patients With Opioid Dependence

This is a 6-month, open-label, multi-center extension study. It is estimated that
approximately 200 patients will be enrolled at approximately 25 sites in the United States
(US). Following completion of either the PRO-807(NCT00630201) or PRO-808 studies, eligible
patients will be implanted with Probuphine implants in the opposite arm for the PRO-809
study. Safety, BPN plasma levels, and efficacy measures will be collected during the 24-week
treatment period.

Inclusion Criteria:

Patients must meet the following eligibility criteria:

- Expected to complete 24 weeks of treatment in PRO-807 or PRO-808

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

- Deemed appropriate for entry into this re-treatment study by the Investigator

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

Exclusion Criteria:

Patients are not eligible for enrollment if any of the following criteria are met:

- 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, measured at the time of the Week 20 Visit for the previous trial (PRO-807 or
PRO-808), or any time less than 5 weeks prior to the Implant Visit.

- Current diagnosis of chronic pain requiring opioids for treatment

- Pregnant or lactating females

- Current use of agents metabolized through cytochrome P450 3A4 (CYP 3A4) such as azole
antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., erythromycin), and
protease inhibitors (e.g., ritonavir, indinavir, and saquinavir)

- Current history of coagulopathy and anti-coagulant therapy (such as warfarin)

- Current use of benzodiazepines other than physician prescribed use

- Significant medical or psychiatric symptoms, cognitive impairment, or other factors
which in the opinion of the Investigator, 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 the study