Dose-ranging Study to Assess Safety and Efficacy of SP-333 for the Treatment of Opioid-induced Constipation (OIC)

Inclusion Criteria:

- Must be receiving chronic, stable opioid therapy to treat non-malignant pain for at
least 3 months prior to screening

- Must have active OIC at screening

- Active OIC must be confirmed during baseline screening bowel habit and symptom diary

- Must be on stable diet

Exclusion Criteria:

- Has history of chronic therapy for chronic constipation prior to start of opioid
therapy, or any potential non-opioid cause of bowel dysfunction that may be a major
contributor to the constipation (i.e., mechanical obstruction or pseudo-obstruction)

- Use of medications that might affect bowel movement frequency or constipation-related
symptoms (e.g., prokinetics, anti-diarrheal agents, laxatives other than study-defined
rescue laxative)

- Has history of or current cancer (other than basal cell or squamous cell carcinoma of
the skin) unless the malignancy has been in complete remission without maintenance
chemotherapy for at least 5 years

- Unstable thyroid disease