A Safety, Tolerability and Pharmacokinetic Dose Escalation Study of HC-ER in Patients With Osteoarthritis Pain

Safety parameters assessed included adverse events, physical examinations, vital signs, 12-lead electrocardiogram (ECGs), clinical laboratory testing and overall Arthritis Pain Intensity and opioid side effects

Inclusion criteria

• Subjects were 18 years or older
• Subjects had osteoarthritis (OA) defined by:

Presence of of typical hip and/or knee joint symptoms. Involvement of at least 1 hip or knee joints that had warranted treatment with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), including cyclooxygenase-2 [COX-2] inhibitors and/or acetaminophen (APAP) for the last 3 months.

Radiographic evidence within the last 6 months of OA in the index joint, with Grade II to IV severity, as illustrated by the Atlas of Standard Radiographs.

• Subjects were otherwise in generally good health, as determined by the investigator, on the basis of medical history, physical examination, electrocardiogram (ECG), and screening laboratory results.
• Female subjects were either physically incapable of childbearing or were practicing an acceptable method of birth control and had a negative pregnancy test result demonstrated before dosing.
• Subjects had experienced a suboptimal response to APAP and NSAID therapy (including COX-2 inhibitor).
• Subjects had used opioids for OA pain on an as needed (PRN) or occasional basis.
• Subjects were willing and able to discontinue or modify their current medication used for management of OA pain per protocol.
• Subjects had steady, not transient, pain and a categorical pain rating of moderate to severe on a scale of none, mild, moderate, or severe.
• Subjects weighed > or = to100 lbs.
• If a subject had taken any inducers or inhibitors of cytochrome P450 [CYP450j), these were discontinued and an appropriate washout period (5 half-lives) had occurred before entry in the study.
• Subjects were able to take oral medication and were willing to comply with the protocol.
• Subjects agreed to abstain from alcohol consumption for the duration of the study.
• Subjects were able to read, understand, and voluntarily sign the IRB approved consent document before the performance of any study-specific procedures.

Exclusion criteria

• Subjects had any clinically significant condition that would, in the investigator's opinion, preclude study participation.
• Subjects had any other clinically significant form of disease at the index joint (study joint) or had been diagnosed with inflammatory arthritis, gout, pseudo-gout, Paget's disease, or any other chronic pain syndrome that, in the investigator's opinion, might interfere with the assessment of pain and other symptoms of OA.
• Subjects had known allergies or previous, significant reactions to opioids.
• Subjects had any laboratory abnormality at screening that was considered clinically significant by the investigator, or that, in the opinion of the investigator, would have contraindicated study participation.
• Subjects were known to have positive test results for human immunodeficiency virus (HIV), hepatitis B antigen, or hepatitis C antibody.
• Subjects had a history of chronic, scheduled opioid use for OA.
• Subjects had any signs or symptoms of opioid withdrawal.
• Subjects had a history of substance or alcohol abuse within 2 years before study entry.
• Subjects tested positively on a urine screen for drugs of abuse.
• Subjects had received any steroid therapy (e.g., oral, intramuscular, intravenous, or soft tissue) within 1 month of study entry.
• Subjects had a condition that would contraindicate the use of opioid analgesia.
• Subjects had participated in a study of an investigational drug or device, or had donated blood, within 30 days before study entry.
• Subjects used any medication that the investigator felt would interact unfavorably with the study medication (e.g., potentiation of sedation with tricyclic antidepressants).
• Subjects had used opioid analgesics for more than 3 days during the 30 days before screening.
• Subjects had a history of seizures.
• Subjects were considered by the investigator to be unsuitable for any reason.