a safety, tolerability and pharmacokinetic dose escalation study of hc-er in patients with osteoarthritis pain

Conditions: Osteoarthrosis

Summary: assess the safety, tolerability and pharmacokinetics of multiple doses of 10, 20, 30, and 40 mg of hydrocodone bitartrate extended release (hc-er)capsules taken with food at steady state, in subjects with chronic, moderate to severe osteoarthritis (oa) 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

Eligibility criteria:
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.

Keywords: safety tolerability pharmacokinetics