Efficacy and Safety Study of NKTR-181 in Opioid-Naive Subjects With Low Back Pain

This is an enriched enrollment, randomized withdrawal study with an open label,
dose-titration period followed by a randomized, double-blind, placebo-control treatment of
twelve weeks. During the double-blind treatment period, this study will evaluate the
analgesic effect of NKTR-181 versus placebo in patients with moderate to severe chronic low
back pain.

Inclusion Criteria:

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

- Clinical diagnosis of moderate to severe, chronic non-neuropathic low back pain for at
least six months

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

- Opioid analgesia is necessary

- Currently taking no more than 10 mg morphine sulfate equivalents per day of short
acting opioids for 14 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:

- Taking extended release or long-acting opioids within 6 months

- History of hypersensitivity, intolerance, or allergy to opioids

- Compression of spinal nerve root; spinal fracture, tumor, or abscess

- Surgical procedures on the low back in the last 12 months or facet nerve root block or
radiofrequency ablation in the last 3 months

- Untreated moderate to severe sleep apnea