Diabetic NeuropathyPhase 3NCT00455520

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

A Phase 3 study testing CG5503 in people with Diabetic Neuropathy, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the effectiveness (level of pain control) and safety of Tapentadol (CG5503) extended release (ER) (base) compared to placebo in patients with moderate to severe pain from diabetic peripheral neuropathy. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetic Neuropathy
What is being tested?: CG5503
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 395 participants
Where: No sites listed yet
Study dates: Apr 2007to Aug 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with Type 1 or Type 2 diabetes mellitus must have a documented clinical diagnosis of painful diabetic peripheral neuropathy with symptoms and signs for at least 6 months, and pain present at the time of screening
The investigator considers the patient's blood glucose to be controlled by diet, or hypoglycemics, or insulin for at least 3 months prior to enrolling in the study (this control should be documented by figures of glycated hemoglobin [HbA1c] no greater than 11% at screening)
Patients have been taking analgesic medications for the condition for at least 3 months prior to screening (patients taking opioid analgesics must be dissatisfied with current treatment, and patients taking non-opioid analgesics must be dissatisfied with current analgesia)
Patients currently requiring opioid treatment must be taking daily doses of an opioid-based analgesic equivalent to <=160 mg of oral morphine

Who cannot join

No significant pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately as in schizophrenia, Alzheimer's disease), or any other clinically significant disease that in the Investigator's opinion may affect efficacy or safety assessments or may compromise patient's safety during trial participation
no history of moderate to severe hepatic impairment such as chronic hepatitis B or C, presence of active hepatitis B or C within the last 3 months or impaired hepatic function with ALT or AST greater than 3-fold ULN
No patients with severely impaired renal function
No laboratory values above or below limits of normal unless considered not clinically relevant by the Investigator
No significant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society (CCS) class III-IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association (NYHA) class III-IV) or significant vascular disease (e.g., peripheral arterial occlusive disease (PAOD) Fontaine class IIb-IV)
no life-long history of seizure disorders or epilepsy

About this study

Official title: A Randomized-Withdrawal Phase 3 Study Evaluating the Safety and Efficacy of CG5503 Extended Release (ER) in Subjects With Painful Diabetic Peripheral Neuropathy

Read the detailed description

The primary objective of this randomized-withdrawal (randomized means study medication assigned to patients by chance and withdrawal means to stop using), multicenter, double-blind (neither patient nor investigator knows the study medication), placebo-controlled, Phase 3 study is to determine the effectiveness and safety of orally administrated Tapentadol (CG5503) extended release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe pain from diabetic peripheral neuropathy. The study is being conducted for registration and approval of CG5503 in the US and outside US. The trial will consist of two phases: Phase I is open-label and Phase 2 is double- blind. In the Open-Label Phase 1 there will be four periods: screening (to assess eligibility), washout (dependent on the pain medication the patient was previously taking), pain intensity perctoris evaluation (over a 3 day period), and open-label titration (study drug will be titrated to an optimal dose starting with 50 mg twice a day and adjusted to an optimal dose for a period of 3 weeks). Patients with at least a 1-point reduction in the average pain intensity score at the end of the open-label titration period, as compared with pre-titration will be eligible for randomization in the double-blind phase. In the double-blind Phase 2, there will be two periods: double-blind maintenance period (take drug for 12 weeks), and follow-up (a visit within 4 days of the intake of the last dose of study drug and a follow-up call approximately 10-14 days after the intake of the last dose of the study drug). The patient will maintain the dose level achieved at the end of the Phase 1 during the double-blind treatment phase. The study hypothesis is that the study drug will be different from placebo in the change in pain intensity. Titrate Tapentadol (CG5503) extended release (ER) 50 mg to patient's optimal dose ranging between 100mg and 250mg twice a day; Placebo (no active ingredients). All doses of trial treatment will be taken orally with or without food, for a maximum timeframe of 15 weeks.

Conditions: Diabetic Neuropathy
Being tested: CG5503, placebo
Keywords: Diabetic neuropathy, Painful Diabetic Polyneuropathy, Polyneuropathy, Peripheral neuropathy
Medical subject headings: Diabetic Neuropathies, Polyneuropathies, Peripheral Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CG5503Drug
100, 150, 200, 250 mg twice daily given for up to 15 weeks
placeboDrug
matching placebo twice daily for 12 weeks

Study groups in NCT00455520
Study group	Role	What they receive
Placebo	Placebo comparator	placebo matching placebo twice daily for 12 weeks Receives: Drug: placebo
CG5503	Experimental	CG5503 100, 150, 200, 250mg twice daily given for up to 15 weeks Receives: Drug: CG5503

What is being measured

The primary outcome is the main question the study is designed to answer.

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
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".
Measured: Baseline and 12 weeks

Secondary outcomes (5)

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.
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.
Measured: Start of Open Label and at 12 weeks of Double Blind
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
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)
Measured: 12 week endpoint
Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12
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.
Measured: 12 week endpoint (change from baseline)
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
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.
Measured: Baseline and 12 week endpoint
Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.
Total pain score where zero equals "no pain" to ten equals "pain as bad as you can imagine" from 12 week endpoint vs baseline.
Measured: Baseline and12 week endpoint

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2007Aug 2008

First posted3 Apr 2007 (estimated)
Study startApr 2007
Primary completionAug 2008
Study completionAug 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Diabetic NeuropathyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 395 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00455520
Sponsor's protocol ID: CR012466
Other IDs: R33133PAI3015
Status last verified: Jul 2013
First submitted: 1 Apr 2007
Last updated: 19 Jul 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
PubMed 23340531
Schwartz S, Etropolski M, Shapiro DY, Okamoto A, Lange R, Haeussler J, Rauschkolb C. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011 Jan;27(1):151-62. doi: 10.1185/03007995.2010.537589.
PubMed 21162697

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 19 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized-Withdrawal Phase 3 Study Evaluating the Safety and Efficacy of CG5503 Extended Release (ER) in Subjects With Painful Diabetic Peripheral Neuropathy
ClinicalTrials.gov ID: NCT00455520
Acronym / sponsor ID: CR012466
Conditions: Diabetic Neuropathy
Keywords: Diabetic neuropathy, Painful Diabetic Polyneuropathy, Polyneuropathy, Peripheral neuropathy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 395 participants (actual)
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.Industry (pharma, biotech, devices)
Collaborators: Grünenthal GmbH
Study start: Apr 2007
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 3 Apr 2007 (estimated)
Results: Posted 13 Jan 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: placeboplacebo matching placebo twice daily for 12 weeks
CG5503	Experimental	Drug: CG5503CG5503 100, 150, 200, 250mg twice daily given for up to 15 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patients with Type 1 or Type 2 diabetes mellitus must have a documented clinical diagnosis of painful diabetic peripheral neuropathy with symptoms and signs for at least 6 months, and pain present at the time of screening
The investigator considers the patient's blood glucose to be controlled by diet, or hypoglycemics, or insulin for at least 3 months prior to enrolling in the study (this control should be documented by figures of glycated hemoglobin [HbA1c] no greater than 11% at screening)
Patients have been taking analgesic medications for the condition for at least 3 months prior to screening (patients taking opioid analgesics must be dissatisfied with current treatment, and patients taking non-opioid analgesics must be dissatisfied with current analgesia)
Patients currently requiring opioid treatment must be taking daily doses of an opioid-based analgesic equivalent to <=160 mg of oral morphine

Key exclusion criteria (6 listed)

No significant pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately as in schizophrenia, Alzheimer's disease), or any other clinically significant disease that in the Investigator's opinion may affect efficacy or safety assessments or may compromise patient's safety during trial participation
no history of moderate to severe hepatic impairment such as chronic hepatitis B or C, presence of active hepatitis B or C within the last 3 months or impaired hepatic function with ALT or AST greater than 3-fold ULN
No patients with severely impaired renal function
No laboratory values above or below limits of normal unless considered not clinically relevant by the Investigator
No significant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society (CCS) class III-IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association (NYHA) class III-IV) or significant vascular disease (e.g., peripheral arterial occlusive disease (PAOD) Fontaine class IIb-IV)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CG5503100, 150, 200, 250 mg twice daily given for up to 15 weeks	Drug	CG5503
placebomatching placebo twice daily for 12 weeks	Drug	Placebo

Primary outcome

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
Time frame: Baseline and 12 weeks
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".

5 secondary outcomes

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.
Time frame: Start of Open Label and at 12 weeks of Double Blind
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
Time frame: 12 week endpoint
Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12
Time frame: 12 week endpoint (change from baseline)
Change From Baseline in Sleep Latency Time in Hours Over the Last Week of the Maintenance Period at Week 12.
Time frame: Baseline and 12 week endpoint
Change From Baseline in Brief Pain Inventory (BPI) Total Pain Score Over the Last Week of the Maintenance Period at Week 12.
Time frame: Baseline and12 week endpoint

Results and safety

Results posted to the registry on 13 Jan 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tapentadol ER	591	395
Placebo	0	0

Primary outcome: 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

Time frame: Baseline and 12 weeks. Mean (Standard Deviation). Unit: scores on a scale

Measure	Tapentadol ER n = 196	Placebo n = 192
Value	-0.1 (1.69)	1.3 (2.41)

Tapentadol ER vs Placebo: Mean Difference (Final Values): -1.3 (95% CI -1.7 to -0.92), p <0.001, ANCOVA

Population analysed: 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.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tapentadol ER	10 of 196 (5.1%)	87 of 196 (44.4%)	Not reported
Placebo	3 of 193 (1.6%)	48 of 193 (24.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23340531Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013 Jan;16(1):27-40.
Derived from this study: PubMed 21162697Schwartz S, Etropolski M, Shapiro DY, Okamoto A, Lange R, Haeussler J, Rauschkolb C. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011 Jan;27(1):151-62. doi: 10.1185/03007995.2010.537589.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial study director

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CG5503 in people with Diabetic Neuropathy, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00455520, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2013.