Opioid-induced Bowel Dysfunction: Pivotal Assessment of Lubiprostone

Inclusion Criteria:

- Consistent treatment for chronic, non-cancer-related pain with any full agonist
opioid for at least 30 days prior to screening.

- Diagnosis of opioid-induced bowel dysfunction (OBD) as confirmed during the screening
period.

- If patient has a history of chronic constipation, condition must have been
exacerbated by initiation of opioid treatment.

- Use of prescribed or Over-the-Counter (OTC) medication that affects gastrointestinal
motility (other than opioid therapy) must be discontinued during the study.

- If treated for clinical depression with Selective serotonin reuptake inhibitor
(SSRIs), Serotonin-norepinephrine reuptake inhibitor (SNRIs), or Monoamine oxidase
inhibitor (MAO) inhibitors, treatment must have been at a stable dose for at least 30
days prior to screening.

- Use of laxative and stool softeners (with the exception of approved rescue
medications) must be discontinued while on study.

Exclusion Criteria:

- Treatment with opioid therapy for cancer-related pain, abdominal pain, scleroderma,
and/or for the management of drug addiction.

- Patient has been treated for cancer in the past 5 years (with the exception of
localized basal cell, squamous cell skin cancer, or in situ cancer that has been
resected).

- Opioid dose adjustment (+/- 30%), and/or change in opioid agent or route of
administration within 30 days of screening.

- Gastrointestinal or abdominal surgical procedures within 90 days prior to screening.

- Non-ambulatory patients, or those who are unable to eat/drink, take oral medications,
or to hold down oral medications due to vomiting.

- Female patients of childbearing potential who are unable/unwilling to use
protocol-specified method(s) of birth control and/or are pregnant, nursing, or plan
to become pregnant or nurse during the study.

- Prior use of Amitiza, lubiprostone, SPI-0211, or RU-0211.