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Study on the Safety and Effectiveness of Switching Between Two Forms of Tapentadol in Patients With Chronic Low Back Pain

Registration Number
NCT00594516
Lead Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Brief Summary

The objective of this study is to test the idea that the immediate-release (IR) form of tapentadol (CG5503) can be directly converted into an approximately equivalent total daily dose (TDD) of the extended-release (ER) form, and vice-versa, with equivalent safety and efficacy.

Detailed Description

This study will establish the dose equivalence and the safety and effectiveness of the Immediate Release (IR) and Extended Release (ER) forms of tapentadol (CG5503) to support the conversion from IR to ER, and ER to IR use. Dose equivalence will be examined in patients diagnosed with moderate-to-severe, chronic Low Back Pain (LBP) requiring drug treatment for at least 3 months, and who are dissatisfied with current therapy. The study consists of 5 periods: a screening period during which patients are evaluated for study eligibility; a 21-day open-label period to find the best, stable dose of tapentadol (CG5503) IR for each patient individually; a 14-day double-blind period when patients are randomly chosen either to continue for 14 days on the stable IR dose from the open-label period or switch to the ER form; a second, 14-day period during which patients switch to whichever form of tapentadol (CG5503) they did not take during the first 14-day period (the total daily dose \[TDD\] remains approximately equivalent for the IR and ER forms throughout both double-blind periods); and a follow-up period. During the study, pain levels will be recorded and overall safety measures taken. The expectation (thought) is that approximately equivalent doses of both forms of tapentadol (CG5503) provide equivalent effectiveness and safety and that the two forms can be directly converted by dividing the total daily dose by the number of times the drug is taken each day. During the 21-day open-label period, 50, 75 or 100mg of the IR form is given orally every 4 or 6 hours, starting with 50mg every 6 hours. Then, the dose, the frequency of giving the drug, or both may be increased, to a maximum TDD of 500mg, or decreased in 50 mg increments, with minimum TDD of 200 mg, until the optimal stable dose for a patient is found. During the 2 double-blind periods, a TDD approximately equivalent to the stable open-label dose is given orally in IR (or ER) form or placebo.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
117
Inclusion Criteria
  • Diagnosis of Low Back Pain (LBP) of non-malignant origin present for at least 3 months immediately before study entry
  • Taking drug treatment for pain for at least 3 months before screening and who are dissatisfied with current therapy
  • Subjects receiving opioid treatment must have a total daily opioid dose <= 160 mg/day of oral morphine equivalent
  • For entry into open label period patients must have a baseline score >=5 on an 11-point NRS, calculated as the average pain intensity during the last 3 days of the washout period
  • For entry into the double-blind period subjects must have remained on the same optimal stable dose and frequency of tapentadol (CG5503) IR administration during the last 3 days of the open-label treatment period
Exclusion Criteria
  • Presence of conditions other than Low Back Pain (LBP) that could make it hard to assess or self-evaluate pain
  • Surgery in low back area within 3 months of screening or expected surgery in the low back area during the study
  • Any scheduled surgery or painful procedure during the study, or any clinically significant disease that, in the opinion of the investigator, may affect efficacy or safety assessments
  • History of malignancy within the past 2 years, with the exception of basal cell carcinoma that has been treated and is no longer present
  • Women who are pregnant or breast-feeding
  • Moderately or severely impaired liver function
  • Severely impaired kidney function
  • History of chronic hepatitis B or C, or HIV, or presence of active hepatitis B or C in past 3 months
  • History of seizure disorder
  • Alcohol or drug abuse
  • Uncontrolled high blood pressure
  • Clinically relevant history of hypersensitivity, allergy, or contraindications to acetaminophen or opioid analgesics (or ingredients)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
002tapentadol (CG5503) Extended Release (ER)tapentadol (CG5503) Extended Release (ER) During 2 double blind periods: Tapentadol ER 100 150 200 or 250 mg tablets twice daily in the first intervention period of double-blind phase and Tapentadol IR in the second or Tapentadol IR in first intervention period of double-blind phase and Tapentadol ER in second
001tapentadol (CG5503) Immediate Release (IR)tapentadol (CG5503) Immediate Release (IR) Following open label period is 2 double blind periods: Tapentadol IR in first intervention period of double-blind phase and Tapentadol ER 100 150 200 or 250 mg tablets twice daily in second or Tapentadol ER in first intervention period of double-blind phase and Tapentadol IR in second,tapentadol (CG5503) Immediate Release IR 21 day Open Label: an adjustable dose of Tapentadol IR 50-100mg orally every 4-6 hours to maximum total daily dose (TDD) dose of 500 mg during open label period
001tapentadol (CG5503) Immediate Release IRtapentadol (CG5503) Immediate Release (IR) Following open label period is 2 double blind periods: Tapentadol IR in first intervention period of double-blind phase and Tapentadol ER 100 150 200 or 250 mg tablets twice daily in second or Tapentadol ER in first intervention period of double-blind phase and Tapentadol IR in second,tapentadol (CG5503) Immediate Release IR 21 day Open Label: an adjustable dose of Tapentadol IR 50-100mg orally every 4-6 hours to maximum total daily dose (TDD) dose of 500 mg during open label period
Primary Outcome Measures
NameTimeMethod
The Difference in the Mean Average Pain Intensity Score on an 11-point Numerical Rating Scale (NRS) During the Last 3 Days of Each Double-blind Treatment Period. (Difference Between Two DB Randomization Treatment Sequences)14 days for each cross-over period

For this twice daily pain assessment, the subjects were to indicate the level of average pain experienced over the previous 12 hours on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".

Secondary Outcome Measures
NameTimeMethod
The Number of Patients Requiring Rescue Medication During the DB Tapentadol IR Treatment14 days for each cross-over period
The Number of Patients Requiring Rescue Medication During the DB Tapentadol ER Treatment14 days for each cross-over period
Total Daily Dose (TDD) of Tapentadol IR During the Double-blind Treatment Period14-day for each DB treatment period

Average total daily dose (TDD) of tapentadol IR during the double blind treatment period

Total Daily Dose (TDD) of Tapentadol ER During the DB Treatment Period.14 days for each treatment period

Average total daily dose (TDD) of tapentadol ER during the double-blind treatment period.

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