Long-Term Safety and Tolerability Study of NKTR-181 in Subjects With Chronic Low Back Pain or Chronic Non-Cancer Pain

This is an open-label safety and tolerability study in which approximately 600 subjects will
receive NKTR-181 for up to 52 weeks. Subjects may include newly enrolled subjects and
subjects who have recently completed SUMMIT-07 or SUMMIT-12 studies.

This study will also investigate the pharmacokinetics of NKTR-181 in patients with chronic
low back pain or chronic non-cancer pain.

Inclusion Criteria:

- Male or non-pregnant, non-nursing female aged 18 to 75 years old

- Clinical diagnosis of moderate to severe, chronic low back or non-cancer pain for at
least three months

- Not experiencing adequate pain relief or have failed previous treatment with
non-opioid analgesics

- Opioid analgesia is necessary

- Currently taking no less than 10 mg but no more than 60 mg of morphine sulfate
equivalents (MSE) per day of opioid analgesics for at least 7 days prior to entry

- Females of child bearing potential must be using a highly effective form of birth
control. All subjects must agree to use double-barrier contraception during
participation in this study and for at least 2 months after the last dose of the study
drug.

- Willing and able to provide informed consent

Exclusion Criteria:

- History of hypersensitivity, intolerance, or allergy to opioids

- Surgical procedures in the last 4 weeks or plans to undergo surgical procedures during
the study period

- Untreated moderate to severe sleep apnea

- Chronic migraines as the primary pain condition

- Cancer related pain