Diabetic Neuropathy, Painful, Diabetic Polyneuropathy
Conditions
Keywords
Diabetic neuropathy, Painful, Polyneuropathy, Peripheral neuropathy
Brief summary
The purpose of this study is to evaluate the safety profile of orally administered tapentadol ER dosages of 100 to 250 mg twice daily in patients with chronic, painful diabetic peripheral neuropathy (DPN) over long-term exposure of up to 1 year.
Detailed description
This is a randomized, open-label, active-controlled, multicenter study evaluating the safety profile of orally administered tapentadol, using the extended release tamper-resistant formulation (TRF), at dosages of 100 to 250 mg twice daily in patients with moderate to severe pain due to chronic, painful DPN. The study consists of 1) a 13-day screening period, a 3-7-day washout period (where patients are to stop taking their pain medication), a 1-day pretitration pain-intensity evaluation period (where patients will record their 24-hour pain intensity), and a 3-week, open-label titration period (patients will receive either tapentadol ER or oxycodone CR study drug in a 3 to 1 ratio), 2) a 49-week, open-label maintenance phase, and 3) a posttreatment phase of approximately 10 to 14 days. The study will evaluate the safety and tolerability of orally administered tapentadol ER by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms (ECGs), opioid withdrawal scales, assessment of patient-reported constipation, standardized neurologic examinations and monitoring of adverse events. Assessments of pain relief include the pain intensity numerical rating scale, and patient global impression of change scale (PGIC). The total duration of study drug treatment for each patient will be approximately 52 weeks. Titrate tapentadol ER 50 mg twice daily or oxycodone CR 10 mg twice daily to patient's optimal dose ranging between 100 mg and 250 mg twice daily or 20 and 50 mg twice daily, respectively. All doses of study medication will be taken orally with or without food for a maximum timeframe of 52 weeks.
Interventions
100, 150, 200, 250 mg twice daily for 52 weeks
DRUGOxycodone controlled release (CR)
20, 30, 40, 50 mg twice daily for 52 weeks
Sponsors
Grünenthal GmbH
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Man or woman aged 18 years or older * Patients with Type 1 or 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 * Diagnosis must include pain plus reduction or absence of pin sensibility and/or vibration sensibility on Total Neuropathy Score - Nurse (TNSn) examination in lower and/or upper extremities at 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 \<=160mg of oral morphine * Patients with baseline score for average pain intensity in the previous 24 hours of =\>4 on the 11-point numerical rating scale (NRS) at the beginning of the titration period
Exclusion criteria
* 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) * History of moderate to severe hepatic impairment * Severely impaired renal function * Clinically significant laboratory abnormalities * Clinically significant cardiac disease * History of seizure disorder or epilepsy * History of any other clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise patient safety during study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-emergent Adverse Events (TEAE) | Entire Study | The number of participants who reported a TEAE during the treatment period. TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 3 days after the discontinuation of the study medication. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tapentadol ER Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 52 weeks | 35 |
| Oxycodone CR Oxycodone controlled release (CR) 20 30 40 50 mg twice daily for 52 weeks | 12 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 7 |
| Overall Study | Study Terminated By Sponsor | 23 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Oxycodone CR | Tapentadol ER | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 9 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 26 Participants | 35 Participants |
| Age, Continuous | 60.1 years STANDARD_DEVIATION 9.23 | 57.5 years STANDARD_DEVIATION 12.41 | 58.2 years STANDARD_DEVIATION 11.64 |
| Region Enroll (United States of America) | 12 participants | 35 participants | 47 participants |
| Sex: Female, Male Female | 2 Participants | 15 Participants | 17 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 35 | 11 / 12 |
| serious Total, serious adverse events | 0 / 35 | 0 / 12 |
Outcome results
Primary
Number of Subjects With Treatment-emergent Adverse Events (TEAE)
The number of participants who reported a TEAE during the treatment period. TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 3 days after the discontinuation of the study medication.
Time frame: Entire Study
Population: Safety analysis set (All randomized participants who took at least one dose of study medication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapentadol ER | Number of Subjects With Treatment-emergent Adverse Events (TEAE) | 23 participants |
| Oxycodone CR | Number of Subjects With Treatment-emergent Adverse Events (TEAE) | 11 participants |