Long Term Safety and Tolerability Study in Approximately 350 Subjects With Moderate to Severe Chronic, Non-malignant Pain

Inclusion Criteria:

• Males and Females between 21 and 75 years of age

  • Females must be of non-child bearing potential or practicing birth control
• Moderate to severe mechanical low back pain OR moderate to severe OA of the hip or knee pain
• Require medicine for pain the majority of days in the previous 3 months, AND for at least 4 days per week, during the previous 4 weeks.
• Pain is not controlled with non-opioid analgesics or is contraindicated due to side effects and/or currently receiving opioid therapy equivalent to 40 mg/day of morphine or less

Exclusion Criteria:

• Pregnant and/or breastfeeding females or females planning to become pregnant during the course of the study
• Incapacitated, bedridden, or confined to a wheelchair permitting little or no self-care
• Injury to the index joint or lower back within 3 months of study

• History of any of the following:

  • Major surgery to the lower back within the last 5 years OR
  • Joint replacement/reconstruction to the index joint OR
  • Arthroscopic or open surgery to the index joint within the last year OR
  • Any surgery within 3 months of study
• Osteoporotic compression fracture, traumatic vertebral fracture or invasive intervention for low back pain within the last year.
• Abnormal neurological exam, or lower extremity symptoms characteristic of neurogenic pain
• History of inflammatory or infectious arthritis, tumors or infections of spinal cord, spinal stenosis, fibromyalgia or other chronic painful condition
• Severe gastrointestinal narrowing
• History of peritonitis, cystic fibrosis, chronic intestinal eudoobstruction, or Meckel's diverticulum.

• Has received

  • Oral, intramuscular (IM), intravenous (IV) or non-index joint intra- articular corticosteroids within 1 month of study OR
  • Intra-articular corticosteroids at the index joint or epidural corticosteroids to the lower back region within 2 months of study, OR
  • Viscosupplementation therapy to index joint within 4 months of study
• History of drug (licit or illicit) or alcohol abuse/addiction
• Positive result for drugs of abuse at screening.
• Chronic heavy drinker, consuming more than 4 alcoholic drinks per day.
• History of malnutrition or starvation or is likely to fast for more than 4 consecutive days during the course of the study.
• Medical condition or illness other than OA/CLBP, which is not well controlled
• History of allergic reaction or a clinically significant sensitivity or intolerance to opioids and/or acetaminophen.
• Newly diagnosed medical condition
• Clinically significant infection/injury/illness within 1 month of study
• Receiving systemic chemotherapy, or has an active malignancy of any type, or has been diagnosed with cancer within the past 5 years. Basal cell carcinoma of the skin that has been successfully treated will be permitted.
• Known or suspected history of Human Immunodeficiency Virus.
• Positive Hepatitis Screen
• Clinically significant abnormalities in clinical chemistry, hematology or urinalysis
• Received any investigational drug within 1 month of study
• History of major psychiatric disorder
• Active or uncontrolled seizure disorder.
• Requires treatment with monoamine oxidase inhibitors (MAOIs), or tricyclic antidepressants during the course of the study.
• Surgical procedure planned, or scheduled during the course of this study.
• Ongoing workman's compensation claim or litigation.
• Previous participation in the M03-666 study.