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

This study has been completed.
Sponsor:
Collaborator:
Grünenthal GmbH
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00455520
First received: April 1, 2007
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Diabetic Neuropathy
Drug: CG5503
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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".


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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)

  • Change From Baseline in EuroQol-5 (EQ-5D) Health Status Index to Week 12 [ Time Frame: 12 week endpoint (change from baseline) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Total pain score where zero equals "no pain" to ten equals "pain as bad as you can imagine" from 12 week endpoint vs baseline.


Enrollment: 395
Study Start Date: April 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
placebo matching placebo twice daily for 12 weeks
Drug: placebo
matching placebo twice daily for 12 weeks
Experimental: CG5503
CG5503 100, 150, 200, 250mg twice daily given for up to 15 weeks
Drug: CG5503
100, 150, 200, 250 mg twice daily given for up to 15 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455520

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Grünenthal GmbH
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00455520     History of Changes
Other Study ID Numbers: CR012466, R33133PAI3015
Study First Received: April 1, 2007
Results First Received: August 19, 2009
Last Updated: July 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Diabetic neuropathy
Painful Diabetic Polyneuropathy
Polyneuropathy
Peripheral neuropathy

Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Diabetic Neuropathies
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 30, 2014