Trial Outcomes & Findings for A Safety and Efficacy Study for Tapentadol (CG5503) Extended Release for Patients With Painful Diabetic Peripheral Neuropathy (NCT NCT00455520)

Last Updated: 2013-07-19

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

395 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2013-07-19

Participant Flow

The recruitment period for this out-patient, multicenter study occurred between 15 March 2007 and 20 August 2008.

The study consisted of a 2-week screening period followed by a 3-week open-label phase where all subjects received tapentadol extended release (ER) and were titrated to an optimal dose, and a 12-week double-blind phase where subjects were randomly assigned to receive tapentadol ER or placebo.

Participant milestones

Participant milestones
Measure	Tapentadol ER Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Open Label Tapentadol Extended Release STARTED	591	0
Open Label Tapentadol Extended Release COMPLETED	395	0
Open Label Tapentadol Extended Release NOT COMPLETED	196	0
Double Blind Tapentadol ER vs Placebo STARTED	196	193
Double Blind Tapentadol ER vs Placebo COMPLETED	133	131
Double Blind Tapentadol ER vs Placebo NOT COMPLETED	63	62

Reasons for withdrawal

Reasons for withdrawal
Measure	Tapentadol ER Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Open Label Tapentadol Extended Release Withdrawal by Subject	24	0
Open Label Tapentadol Extended Release Lost to Follow-up	3	0
Open Label Tapentadol Extended Release Adverse Event	100	0
Open Label Tapentadol Extended Release Lack of Efficacy	23	0
Open Label Tapentadol Extended Release Study drug non-compliant	13	0
Open Label Tapentadol Extended Release All other	33	0
Double Blind Tapentadol ER vs Placebo Adverse Event	29	15
Double Blind Tapentadol ER vs Placebo Lack of Efficacy	8	29
Double Blind Tapentadol ER vs Placebo Withdrawal by Subject	15	7
Double Blind Tapentadol ER vs Placebo Lost to Follow-up	3	3
Double Blind Tapentadol ER vs Placebo Study drug non compliant	4	2
Double Blind Tapentadol ER vs Placebo All other	4	6

Baseline Characteristics

A Safety and Efficacy Study for Tapentadol (CG5503) Extended Release for Patients With Painful Diabetic Peripheral Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tapentadol ER n=196 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=193 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.	Total n=389 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	136 Participants n=5 Participants	120 Participants n=7 Participants	256 Participants n=5 Participants
Age, Categorical >=65 years	60 Participants n=5 Participants	73 Participants n=7 Participants	133 Participants n=5 Participants
Age Continuous	59.9 years STANDARD_DEVIATION 10.68 • n=5 Participants	60.6 years STANDARD_DEVIATION 10.56 • n=7 Participants	60.2 years STANDARD_DEVIATION 10.62 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	77 Participants n=7 Participants	154 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants	116 Participants n=7 Participants	235 Participants n=5 Participants
Region of Enrollment United States	191 participants n=5 Participants	189 participants n=7 Participants	380 participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat (ITT) analysis set included all randomized subjects who took at least one dose of study medication during the double blind maintenance period with the exception of 3 subjects who were enrolled in the study twice.

Outcome measures

Outcome measures
Measure	Tapentadol ER n=196 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=192 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Change From Baseline (at Randomization) in Average Pain Intensity on an 11-point Numerical Rating Scale (NRS) Over the Last Week of the Double-blind Maintenance Period at Week 12	-0.1 scores on a scale Standard Deviation 1.69	1.3 scores on a scale Standard Deviation 2.41

SECONDARY outcome

Timeframe: Start of Open Label and at 12 weeks of Double Blind

Population: Intent-to-treat analysis set.

The number of patients achieving at least 30% improvement in pain score at Week 12 of the double-blind maintenance period on an 11-point numerical rating scale compared with the start of the open-label period.

Outcome measures

Outcome measures
Measure	Tapentadol ER n=196 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=192 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
The Number of Patients Achieving at Least 30% Improvement in Pain Score at Week 12 of the Double-blind Maintenance Period From the Start of the Open Label Period.	105 participants	81 participants

SECONDARY outcome

Timeframe: 12 week endpoint

Percentage of patients who reported very much improved (1) or much improved (2) based on an ordinal measure indicating change from start of double blind treatment (on a scale of 7 = Very much worse to 1 = Very much improved)

Outcome measures

Outcome measures
Measure	Tapentadol ER n=177 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=180 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
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	64 percentage of patients	38 percentage of patients

SECONDARY outcome

Timeframe: 12 week endpoint (change from baseline)

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=195 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=192 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12	0.7 scores on a scale Standard Deviation 0.21	0.6 scores on a scale Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline and 12 week endpoint

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=133 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=143 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
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 3.22	-0.59 Hours Standard Deviation 2.77

SECONDARY outcome

Timeframe: Baseline and12 week endpoint

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=194 Participants Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=192 Participants Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.	-3.1 Scores on a scale Standard Deviation 2.13	-2.2 Scores on a scale Standard Deviation 2.17

Adverse Events

Tapentadol ER

Serious events: 10 serious events

Other events: 87 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tapentadol ER n=196 participants at risk Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=193 participants at risk Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Gastrointestinal disorders Nausea	13.8% 27/196 • 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.	6.2% 12/193 • 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 Diarrhoea	8.2% 16/196 • 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% 8/193 • 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	6.6% 13/196 • 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.	1.0% 2/193 • 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 Constipation	6.1% 12/196 • 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.	1.0% 2/193 • 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	7.7% 15/196 • 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% 3/193 • 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	5.1% 10/196 • 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% 10/193 • 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 Anxiety	9.2% 18/196 • 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% 8/193 • 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 Restlessness	5.6% 11/196 • 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% 8/193 • 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	5.1% 10/196 • 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.	3.6% 7/193 • 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.
Musculoskeletal and connective tissue disorders Myalgia	6.6% 13/196 • 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% 14/193 • 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.
Musculoskeletal and connective tissue disorders Bone pain	4.1% 8/196 • 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% 10/193 • 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

Phone: 609-730-4537

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication. The sponsor can embargo for an additional 60 days to allow for the filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tapentadol ER n=196 participants at risk Tapentadol ER dose of 100 to 250mg twice a day (BID) for 12 weeks during the double blind period. The study medication was provided as tablets taken orally.	Placebo n=193 participants at risk Placebo tablets taken orally twice a day (BID) for 12 weeks during the double blind period.
Infections and infestations Helicobacter gastritis	0.51% 1/196 • 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% 0/193 • 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.
Infections and infestations Pneumonia	0.51% 1/196 • 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% 0/193 • 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.
Infections and infestations Prostate infection	0.51% 1/196 • 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% 0/193 • 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.
Infections and infestations Urinary tract infection	0.51% 1/196 • 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% 0/193 • 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.
Infections and infestations Urosepsis	0.51% 1/196 • 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% 0/193 • 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.
Metabolism and nutrition disorders Dehydration	0.51% 1/196 • 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% 0/193 • 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.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.51% 1/196 • 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.	0.52% 1/193 • 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.
Metabolism and nutrition disorders Hypokalemia	0.51% 1/196 • 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% 0/193 • 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.
Cardiac disorders Angina unstable	0.51% 1/196 • 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% 0/193 • 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 Asthenia	0.51% 1/196 • 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% 0/193 • 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 Chest pain	0.00% 0/196 • 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.	0.52% 1/193 • 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.
Investigations Blood glucose increased	0.51% 1/196 • 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% 0/193 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.51% 1/196 • 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% 0/193 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/196 • 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.	0.52% 1/193 • 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 Suicidal ideation	0.51% 1/196 • 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% 0/193 • 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.
Vascular disorders Venous thrombosis	0.51% 1/196 • 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% 0/193 • 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.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/196 • 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.	0.52% 1/193 • 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.