Efficacy and Safety of Tapentadol Extended Release Tablets in the Treatment of Moderate to Severe Pain in Subjects With Knee Osteoarthritis

4-Week Randomized Multicenter DB, Placebo- and Active-controlled, Parallel-group, Forced-titration Phase 2B Study of Efficacy and Safety With CG5503 Prolonged Release (PR) to 233 mg BID and Oxycodone PR to 20 mg BID vs Placebo in Subjects With Moderate to Severe Chronic Pain of 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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Knee Pain; Osteoarthitis
• Intervention / Treatment: Drug: tapentadol HCl

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 670
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Average pain intensity over the preceding 24 hours evaluated at the last timepoint or 29 days using a visual scale.

Secondary Outcome Measures

Outcome Measure
Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at the last timepoint or 29 days

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Grünenthal GmbH

Publications and helpful links

General Publications

• Eichenbaum G, Gohler K, Etropolski M, Steigerwald I, Pergolizzi J, Kim M, Vorsanger G. Does tapentadol affect sex hormone concentrations differently from morphine and oxycodone? An initial assessment and possible implications for opioid-induced androgen deficiency. J Opioid Manag. 2015 May-Jun;11(3):211-27. doi: 10.5055/jom.2015.0270.

Helpful Links

• Efficacy and safety of tapentadol extended release tablets in the treatment of moderate to severe pain in subjects with knee osteoarthritis

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: August 29, 2008
• First Submitted That Met QC Criteria: August 29, 2008
• First Posted (Estimate): September 1, 2008

Study Record Updates

• Last Update Posted (Estimate): May 18, 2011
• Last Update Submitted That Met QC Criteria: May 17, 2011
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: Osteoarthritis; Chronic pain; Analgesia; Tapentadol
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Chronic Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Tapentadol
• Other Study ID Numbers: CR004183