A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Relieving Opioid-Induced Constipation (OIC) in Patients With Cancer-Related Pain

Inclusion Criteria:

- Provision of written informed consent prior to any study-specific procedures.

- Men and women aged 18 or older.

- Histologically or cytologically confirmed neoplasm causing pain and requiring
management with opioids.

- Self-reported active symptoms of OIC at screening (<3 RFBMs/week and experiencing >1
reported symptom of hard/lumpy stools, straining, or sensation of incomplete
evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks);
and Documented confirmed OIC (<3 RFBMs/week on average aver the 2-week OIC
confirmation period.

- Receiving a stable maintenance opioid regimen consisting of a total daily dose of >30
mg of oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies for a
minimum of 4 weeks prior to screening for cancer-related pain with no anticipated
change in opioid dose requirement over the proposed study period as a result of
disease progression.

Exclusion Criteria:

- Patients receiving Opioid regimen for treatment of pain other than related to cancer.

- Any condition that may have affected the permeability of the blood-brain barrier, eg,
known brain metastases, meningeal metastases, brain injury, multiple sclerosis,
recent brain injury, uncontrolled epilepsy.

- Patients with cancer-related pain due to ovarian cancer, leukaemia, or lymphoma are
excluded. Patients with multiple myeloma will be allowed.

- Patients requiring radiation therapy between the diaphragm and pelvis 4 weeks prior
to Visit 1 (screening) and/or during Part A of the study are excluded. Any patients
with suspected clinically relevant radiation-induced injury of small or large
intestine are excluded.

- Pregnancy or lactation.