Efficacy and Safety of Tapentadol Extended Release Tablets in the Treatment of Moderate to Severe Pain in Subjects With Knee Osteoarthritis
Efficacy and Safety of Tapentadol Extended Release Tablets in the Treatment of Moderate to Severe Pain in Subjects With Knee Osteoarthritis
The purpose of this study was to examine a low and high dose of tapentadol extended release
 tablet taken orally twice a day to reduce pain in subjects suffering from chronic moderate to
 severe pain due to osteoarthritis of the knee during a 4-week period. Subjects steadily
 increased their dose up to the low (100 mg) or high (200 mg) dose. Pain relief was compared
 to subjects taking placebo tablets or oxycodone extended release tablet, 20 mg. The serum
 concentrations and safety of tapentadol and oxycodone were also examined.
Arthritis is the most common chronic debilitating disease in the United States (more than 43
 million people or 1 in 6). Osteoarthritis of the knee is a very common and a major cause of
 disability. Pharmacological treatment includes the following analgesics: non-steroidal
 anti-inflammatory drugs (NSAIDs), cyclo-oxygenase II (COX-II) inhibitors, acetaminophen and
 opioids. Despite the numerous available analgesic medications, 60% to 80% of patients
 suffering from chronic pain are currently treated inadequately. Opioid analgesics have been
 shown to be efficacious in chronic non-malignant pain and can be an important therapeutic
 asset. The study was a 4-week randomized multicenter double-blind, placebo- and
 active-controlled, parallel-group, forced-titration phase 2B study of efficacy and safety
 with tapentadol extended release (ER) to 233 mg BID and oxycodone PR to 20 mg BID vs placebo
 in subjects with moderate to severe chronic pain of knee osteoarthritis. Primary efficacy
 outcome was the average pain intensity 24 hours before the last evaluation time or 29 days.
 Safety was evaluated by reporting of adverse events, laboratory tests, vital sign measures,
 ECGs. This study hypothesis was that tapentadol extended release was effective in relieving
 chronic moderate to severe pain from knee osteoarthritis compared to treatment with placebo
 using 2 dosing regimens for tapentadol.

 tapentadol extended release white, fim-coated tablet taken orally twice a day during a 4-week
 period at a dose that steadily increased up to 100 mg or 200 mg; placebo tablets; or
 oxycodone extended release tablet, 20 mg.
Inclusion Criteria:

 -  Subjects with a clinical diagnosis of osteoarthritis of the knee based symptoms and/or
 radiographic criteria present for at least 3 months

 -  Moderate to severe chronic pain due to knee osteoarithritis

 Exclusion Criteria:

 -  Previously opioid treated subject who had a history of withdrawal after cessation of
 the opioid

 -  History of seizure disorder, psychiatric disease and history of head trauma requiring
 evaluation by hospital based staff, or unconsciousness of unknown origin. Subjects
 who, in the investigator's judgment, have well-controlled depression or anxiety
 disorder may participate

 -  Subjects with history of uncontrolled hypertension (systolic blood pressure > 160 mmHg
 or diastolic blood pressure > 95 mmHg)

 -  Intake of tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors,
 barbiturates, neuroleptics, monoamine oxidase inhibitors, and antiparkinsonian drugs
 within the 30 days prior to the screening visit