A Randomized Withdrawal, Active- and Placebo-controlled, Double-blind, Multi-center Phase III Trial Assessing Safety and Efficacy of Oral CG5503 (Tapentadol) Prolonged Release (PR*) in Subjects With Moderate to Severe Chronic Malignant Tumor-related Pain. *Prolonged Release and is the Recommended Nomenclature for Use in the European Union (EU). ER Means Extended Release and is the Recommended Nomenclature for Use in the United States of America (USA). "PR" is Synonymous With "ER" and is Interchangeable.
Normally chronic tumor related pain is controlled when subjects receive repeated doses of
opioid analgesics. However, opioid therapy is commonly associated with side effects such as
nausea, vomiting, sedation, constipation, addiction, tolerance, and respiratory depression.
Tapentadol, a newly synthesized drug with an Prolonged Release (ER) formulation, also acts
as a centrally acting pain reliever but has a dual mode of action.
The aim of this trial is to investigate the effectiveness (level of pain control) and safety
(side effects) of Tapentadol Prolonged Release (ER) compared to a tablet with no active
ingredient drug (placebo) and a corresponding dose of Morphine (an opioid commonly used to
treat tumor related pain). This trial is a randomized, double-blind (neither investigator
nor patient will know which treatment was received), active- and placebo-controlled,
parallel-group, multicenter trial.
The trial includes a 2 week titration phase starting with either 45 mg Morphine Sulfate
Controlled Release (CR) twice daily or 100 mg Tapentadol ER taken twice daily (bid). Based
on effectiveness and side effects subjects can up-titrate in steps of 50 mg Tapentadol ER or
15 mg Morphine Sulfate CR to a maximal dose of 250 mg Tapentadol ER bid or 90 mg Morphine
Sulfate CR twice daily respectively. If subjects meet the stabilization criteria at the end
of the titration phase they will be re-randomized to either placebo or active treatment and
will continue 4 weeks at the last dose level in the maintenance phase.
Assessments of pain relief, defined as a responder include the pain intensity numeric rating
scale (NRS). The Patient Global Impression of Change scale (PGIC) will also be used as a
secondary efficacy endpoint. Safety evaluations include monitoring of adverse events,
physical examinations, and clinical laboratory tests. Venous blood samples will be collected
for the determination of serum concentrations of tapentadol.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
A "responder" is a participant in the study that: completed 28 days of the maintenance phase had a numeric rating scale score below 5 on the 11 point scale (where 0 indicates no pain and 10 indicates worst possible pain) did not use more than 30 mg of rescue medication per day on average in the 28 day maintenance period. A participant that met all 3 of the above-mentioned criteria is counted as a responder, in other words the participant benefited from the assigned drug treatment. A participant that fails to meet only 1 of the 3 criteria is not counted as a responder.
completed 28 days in the maintenance phase
P. Poulain, Dr.
Gustave Roussy, Cancer Campus, Grand Paris
United States: Food and Drug Administration
|Investigator 13||St. Petersburg, Florida|
|Investigator 2||Elkhart, Indiana|
|Investigator 1||Shreveport, Louisiana|
|Investigator 10||Cedarhurst, New York|
|Investigator 3||Glen Falls, New York|
|Investigator 4||Winston-Salem, North Carolina|
|Investigator 15||Canton, Ohio|