Single-arm Study to Assess the Safety of Hydromorphone Hydrochloride by Intrathecal Administration

This is an open-label, single-arm safety study to evaluate the safety of hydromorphone
hydrochloride given by continuous intrathecal infusion using an implantable pump device.
This study will enroll both subjects on a current opioid intrathecal medication as well as
naïve subjects now current on intrathecal opioid medications. All subjects currently on
intrathecal opioid treatment will be converted from their current intrathecal therapy to
intrathecal hydromorphone hydrochloride according to standard medical practice. After an
optimal dose for pain relief is achieved, subjects will remain on therapy for a total of 12
months or until discontinuation from the study. During this continuous dosing period, dose
adjustments (up or down) are permitted to manage pain or side effects provided a maximum
dose of 10 mg/day is not exceeded. Subjects will be assessed for pain intensity using a
visual analog scale of pain intensity (VASPI) instrument at each study visit.

Subjects will be evaluated for side effects and clinical complications associated with the
use of intrathecal hydromorphone. Events will be classified by intrathecal drugs used and
concentrations.

Inclusion Criteria:

Subjects must meet all of the following criteria to be included:

1. Subjects must be at least 18 years of age and no more than 75 years old.

2. Clinically diagnosed with severe chronic pain for at least a 6-month period.

3. Subject is reasonably expected to benefit from intrathecal pain medication and has a
programmable implantable intrathecal pump or meets clinical criteria for implantation
of an intrathecal pump per Standard of Care.

4. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting
narcotic prescriptions to the study medication prescribed by the investigator.

5. Subject must be cognitively intact and, in the opinion of the investigator, capable
of participation in the trial.

6. Female subjects of child-bearing potential must agree to use a medically acceptable
and effective double-barrier method of birth control.

7. Subjects who can receive an MRI if required by the study protocol.

8. Provides written Ethics Committee approved informed consent.

9. Willing to comply with all study procedures and requirements.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded:

1. Women who are pregnant or breast-feeding.

2. Subject has any known or suspected allergy to hydromorphone hydrochloride or to the
materials of the infusion pump or intrathecal catheter.

3. Subject has a history of dependence and abuse of opioids, stimulants, alcohol, or
benzodiazepines, as defined by DSM-IV criteria, within the past year (physical
dependence on prescribed opioid analgesics is allowed but abuse of opioids according
to DSM-IV is not permitted, i.e. opioid addiction for recreational use).

4. Subjects who show signs of active systemic infection.

5. Subjects with a metastatic cancer to the spinal canal or a known central nervous
system contraindication to intrathecal therapy.

6. Subjects have a condition requiring diathermy procedures.

7. Subject has a life expectancy of less than 12 months.

8. Subjects who are unable or unwilling to return to all of the required follow-up
visits.

9. As a result of medical review and physical examination, the Investigator considers
the subject unfit for the study.