Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

Inclusion Criteria:

- Patient has chronic non-cancer pain that has been present for a minimum of 3 months

- Patient has been receiving a stable dose of a full-opioid agonist for at least 4 days
per week during the 8 consecutive weeks

- Patient meets protocol criteria for Opioid-Induced Constipation (OIC): < 3
spontaneous bowel movements (SBMs) per week and reports one of the following symptoms
for at least 4 weeks:

1. Straining during > 25% of BMs

2. Lumpy or hard stools during > 25% of BMs

3. Sensation of incomplete evacuation during > 25% of BMs

- Patient meets the colonoscopy requirements defined by the American
Gastroenterological Association guidelines

- Patient has successfully completed protocol procedures (with no clinically
significant findings)

- Patient is compliant with Interactive Voice Response System (IVRS) for daily diary
reporting

- Patient has a total of < 6 SBMs in IVRS during the 14 days before and up to the time
of Randomization

- Patient has adequate relief and well-controlled pain with current dose of opioid

Exclusion Criteria:

- Patient has been using opioids for abdominal pain

- Patient has symptoms of or been diagnosed with chronic constipation or chronic
idiopathic constipation prior to initiation of opioid treatment

- Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS) prior
to initiation of opioid treatment

- Patient has a history of loose or watery stools for > 25% of BMs during the 3 months
before the Screening in the absence of laxatives, suppositories, or enemas

- Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease
or condition that can affect GI motility

- Patient has any protocol-excluded or clinically significant medical or surgical
history that would limit the patient's ability to complete or participate in this
clinical trial or could confound the study assessments