Trial Outcomes & Findings for A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) Extended Release (ER) in Patients With Moderate to Severe Chronic Low Back Pain (NCT NCT00449176)

Last Updated: 2012-04-30

Results Overview

For this twice daily pain assessment, the subjects were to indicate the level of 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".

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

981 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2012-04-30

Participant Flow

The recruitment period for this out-patient, multicenter study occurred between 21 February 2007 and 12 March 2008.

The study consisted of a screening period (duration up to 14 days), a washout period (duration 3 to 7 days), a double-blind active treatment period with titration period (duration 3 weeks) and maintenance period (duration 12 weeks).

Participant milestones

Participant milestones
Measure	Tapentadol ER Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo Matching Placebo twice daily(BID)
Overall Study STARTED	318	328	319
Overall Study COMPLETED	166	133	152
Overall Study NOT COMPLETED	152	195	167

Reasons for withdrawal

Reasons for withdrawal
Measure	Tapentadol ER Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo Matching Placebo twice daily(BID)
Overall Study Withdrawal by Subject	39	43	59
Overall Study Lost to Follow-up	13	8	12
Overall Study Adverse Event	51	107	15
Overall Study Lack of Efficacy	13	7	50
Overall Study Study drug non-compliant	14	11	11
Overall Study all other	22	19	20

Baseline Characteristics

A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) Extended Release (ER) in Patients With Moderate to Severe Chronic Low Back Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tapentadol ER n=318 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=328 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=319 Participants Matching Placebo twice daily(BID)	Total n=965 Participants Total of all reporting groups
Age Continuous	49.4 years STANDARD_DEVIATION 13.21 • n=5 Participants	50.0 years STANDARD_DEVIATION 14.21 • n=7 Participants	50.4 years STANDARD_DEVIATION 14.05 • n=5 Participants	49.9 years STANDARD_DEVIATION 13.83 • n=4 Participants
Sex: Female, Male Female	194 Participants n=5 Participants	181 Participants n=7 Participants	184 Participants n=5 Participants	559 Participants n=4 Participants
Sex: Female, Male Male	124 Participants n=5 Participants	147 Participants n=7 Participants	135 Participants n=5 Participants	406 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent To Treat (ITT) analysis set utilizing Last Observation Carried Forward (LOCF) imputation. The ITT analysis set included all randomized patients that took at least one dose of study medication following randomization. 7 patients (3 tapentadol ER, 3 oxycodone CR, 1 placebo) had no baseline pain scores therefore excluded from the analysis.

Outcome measures

Outcome measures
Measure	Tapentadol ER n=312 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=323 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=316 Participants Matching Placebo twice daily(BID)
Change From Baseline of the Average Pain Intensity Based on a 11-point Numerical Rating Scale (NRS) Over the Last Week of the Maintenance Period at Week 12.	-2.9 scores on a scale Standard Deviation 2.66	-2.9 scores on a scale Standard Deviation 2.52	-2.1 scores on a scale Standard Deviation 2.33

SECONDARY outcome

Timeframe: Baseline and 12 week endpoint

Population: Intent to Treat (ITT) analysis set, last observation carried forward (LOCF) imputation. The ITT analysis set included all randomized patients that took at least one dose of study medication following randomization. The patients who didi not have any assessment during the treatment period were excluded from the analysis.

Total pain score where zero equals "no pain" to ten equals "pain as bad as you can imagine" from 12 week endpoint vs baseline.

Outcome measures

Outcome measures
Measure	Tapentadol ER n=314 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=323 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=314 Participants Matching Placebo twice daily(BID)
Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.	-2.3 scores on a scale Standard Deviation 2.25 • Interval -1.06 to -0.37	-2.1 scores on a scale Standard Deviation 2.35 • Interval -0.88 to -0.2	-1.6 scores on a scale Standard Deviation 2.11

SECONDARY outcome

Timeframe: Baseline and 12 week endpoint

Population: Intent to Treat population with LOCF imputation. The patients who didi not have any assessment during the treatment period were excluded from the analysis.

A Sleep Questionnaire addressed the following question: "How long after bedtime/lights out did you fall asleep last night (hours)?" 12 week endpoint-mean changes from baseline at endpoint for sleep latency. Decrease in time(hours) indicates improvement.

Outcome measures

Outcome measures
Measure	Tapentadol ER n=311 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=324 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=312 Participants Matching Placebo twice daily(BID)
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.	-0.2 hours Standard Deviation 3.08	-0.2 hours Standard Deviation 2.32	-0.1 hours Standard Deviation 2.43

SECONDARY outcome

Timeframe: Baseline and 12 week endpoint

Population: Intent to Treat Analysis (ITT) set, Last Observation Carried Forward (LOCF) imputation method. The ITT analysis set included all randomized subjects who took at least one dose of study medication following randomization. The patients who didi not have any assessment during the treatment period were excluded from the analysis.

Ordinal measure indicating change from start of treatment (On a scale of 7 = Very much Worse to 1 = very much improved)

Outcome measures

Outcome measures
Measure	Tapentadol ER n=236 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=210 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=245 Participants Matching Placebo twice daily(BID)
Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change Over the Last Week of the Maintenance Period at Week 12	55.5 percentage of participants	60 percentage of participants	32.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Analysis Set

The number of participants who discontinued due to lack of efficacy from baseline to endpoint

Outcome measures

Outcome measures
Measure	Tapentadol ER n=315 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=326 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=317 Participants Matching Placebo twice daily(BID)
Number of Participants With Treatment Discontinuation Due to Lack of Efficacy	18 participants	9 participants	64 participants Interval 33.0 to

SECONDARY outcome

Timeframe: Baseline and 12 week endpoint

Population: Intent to Treat Analysis Set, LOCF imputation method. The patients who didi not have any assessment during the treatment period were excluded from the analysis.

Change from baseline to end point in EuroQol-5 Dimension Questionnaire. A higher score indicates an improvement in health in the Health Status Index. The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead.

Outcome measures

Outcome measures
Measure	Tapentadol ER n=315 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=325 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=316 Participants Matching Placebo twice daily(BID)
Change From Baseline in EuroQol-5® (EQ-5D) Health Status Index to Week 12	0.2 scores on a scale Standard Deviation 0.3	0.2 scores on a scale Standard Deviation 0.33	0.1 scores on a scale Standard Deviation 0.33

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent to Treat Analysis Set

Defined by the proportion of subjects achieving at least 50% improvement from baseline in the primary endpoint of change from baseline of the average pain intensity based on the 11-point Numerical Rating Scale (NRS) at week 12. The subjects were to indicate the level of pain experienced over the previous 12 hours on an 11-point NRS where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".

Outcome measures

Outcome measures
Measure	Tapentadol ER n=315 Participants Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=326 Participants oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=317 Participants Matching Placebo twice daily(BID)
Responder Analysis 50% Improvement	27.0 Percentage of participants	23.3 Percentage of participants	18.9 Percentage of participants

Adverse Events

Tapentadol ER

Serious events: 8 serious events

Other events: 192 other events

Deaths: 0 deaths

Oxycodone CR

Serious events: 11 serious events

Other events: 240 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 118 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tapentadol ER n=318 participants at risk Tapentadol (CG5503) extended release(ER) 100-250mg twice daily(BID)	Oxycodone CR n=328 participants at risk oxycodone controlled release(CR) 20-50mg twice daily(BID)	Placebo n=319 participants at risk Matching Placebo twice daily(BID)
Gastrointestinal disorders Constipation	13.8% 44/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	26.8% 88/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	5.0% 16/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Gastrointestinal disorders Diarrhea	6.0% 19/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	2.4% 8/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	7.2% 23/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Nervous system disorders Dizziness	11.9% 38/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	16.8% 55/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	5.6% 18/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Gastrointestinal disorders Dry Mouth	8.2% 26/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	3.7% 12/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	2.2% 7/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Gastrointestinal disorders Dyspepsia	5.0% 16/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	1.8% 6/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	2.5% 8/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
General disorders Fatigue	6.6% 21/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	7.3% 24/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	4.1% 13/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Nervous system disorders Headache	19.8% 63/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	16.8% 55/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	13.8% 44/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.8% 12/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	5.2% 17/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	0.00% 0/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Psychiatric disorders Insomnia	4.1% 13/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	7.6% 25/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	2.8% 9/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Gastrointestinal disorders Nausea	20.1% 64/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	34.5% 113/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	9.1% 29/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	7.2% 23/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	16.8% 55/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	1.9% 6/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Nervous system disorders Somnolence	13.2% 42/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	16.2% 53/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	2.5% 8/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.
Gastrointestinal disorders Vomiting	9.1% 29/318 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	19.2% 63/328 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.	1.6% 5/319 • All adverse events were reported from the time a signed and dated informed consent was obtained throughout the follow-up phase of the study. Serious adverse events were collected for 30 days after the last dose of study drug.

Additional Information

Senior Director, Clinical Leader

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Phone: 609-730-4537

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60