Chronic neuropathic pain in patients with diabetic peripheral neuropathy MedDRA version: 9.1 Level: LLT Classification code 10054095 Term: Neuropathic pain
Conditions
Sponsors
XTL Development Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, of any race, age 18 years or older 2. Diagnosis of type-I (insulin dependent) or type-II (non-insulin dependent) diabetes mellitus 3. Hemoglobin A1C of =11% 4. Evidence of chronic bilateral pain due to diabetic neuropathy, which is defined as pain in the legs or feet with decreased sensation in the feet or decreased/absent ankle jerk deep tendon reflexes 5. Neuropathy diagnosis confirmed by a score of =3 on the Michigan Neuropathy Screening Instrument (MNSI) Part B only. 6. Presence of pain due to chronic diabetic neuropathy for at least 6 months prior to the initial screening visit 7. The primary pain location must be in the feet 8. For females, subjects of childbearing potential (including peri-menopausal women who have had a menstrual period within 1 year) must be using appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly, such as implants, injectable, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner). Oral contraceptive medications are allowed in this study 9. Subject must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures 10. Subject must give written informed consent to participate. There must be evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent procedures of the study prior to performing any study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of other pain that could confound assessment or self-evaluation of the pain due to chronic diabetic neuropathy such as peripheral vascular disease (ischemic pain), neurological disorders unrelated to diabetic neuropathy (e.g., phantom limb pain from amputation), skin condition in the area of the neuropathy that could alter sensation (e.g., plantar ulcer), or other painful conditions (e.g., arthritis, fibromyalgia) 2. Symptoms of other painful conditions such as thoracic radiculopathy or lumbar radiculopathy that could confound assessment or self-evaluation of the pain due to chronic diabetic neuropathy 3. Presence of amputations other than toe amputations 4. History of lack of analgesic response to an adequate trial of duloxetine, venlafaxine, or tricyclic antidepressants (TCAs) 5. Score of >20 on the BDI 6. History of any clinically significant psychiatric or other neurological disorder other than diabetic neuropathy, headache, or migraine headache 7. Significant neurological or psychiatric symptoms resulting in disorientation, memory impairment, or inability to report accurately (e.g., Alzheimer’s disease or schizophrenia or other psychosis), that in the investigator’s opinion may affect efficacy or safety assessments or may compromise subject safety during the trial 8. History (within the last 10 years) of any seizure disorder or epilepsy 9. Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within the last 10 years 10. Use of the following medications (which could affect symptoms of pain due to chronic diabetic neuropathy) during the study: TCAs, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin, other AEDs (such as carbamazepine), baclofen, mexiletine, capsaicin, tramadol, opioids, or other analgesics (except for acetaminophen up to 3 g/day and prophylactic aspirin up to 325 mg/day). All of these excluded medications require a washout period of appropriate length (according to the investigator) before the Screening II Visit. 11. Current evidence of clinically important diseases of gastrointestinal, hematopoietic, renal, respiratory, or cardiovascular systems; urinary retention; or glaucoma 12. Female subjects who are pregnant and/or breastfeeding or have a positive serum pregnancy test at the Screening or Baseline Visits 13. Positive urine drug screen for amphetamines, barbiturates, marijuana metabolites, cocaine metabolites, methadone, methaqualone, opiates, phencyclidine (PCP), or propoxyphene. However, a positive urine drug screen for benzodiazepines will not necessarily exclude the subject. 14. History of known alcohol or narcotic substance abuse within 2 years prior to the initial screening visit 15. History of any chronic illness other than diabetes that may interfere with or contraindicate participation in the study, as determined by the investigator 16. A body mass index (BMI) of greater than 40 17. Clinically-relevant illness within the 30 days prior to the initial screening visit that may interfere with the subject’s ability to complete the study 18. Participated in a previous clinical study of bicifadine 19. Any subject considering or scheduled to undergo any major surgical procedure during the study period 20. Any subject who has taken any other investigational drug during the 30 days prior to the initial screening v
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the efficacy of 2 dosages (600 mg/day and 1200 mg/day) of bicifadine sustained release (SR) with placebo in reduction of chronic neuropathic pain (measured by a daily rating of pain intensity) associated with diabetic peripheral neuropathy (DPN) in adult outpatients 2. To compare the tolerability of 2 dosages (600 mg/day and 1200 mg/day) of bicifadine SR with placebo in adult outpatients treated for chronic neuropathic pain associated with DPN ;Secondary Objective: 1. To compare the efficacy of treatment with 2 dosages of bicifadine SR with placebo on the following secondary efficacy measures: • proportion of responders, defined as =30% reduction from Baseline to Week 14 in weekly mean of daily ratings of pain intensity • change from Baseline in scores on the following pain-related measures: - Brief Pain Inventory score - Clinical Global Impression of Improvement rating - Patient Global Impression of Change rating - Short Form McGill Pain Questionnaire Form X scores • the amount of rescue medication used for pain • change from Baseline in depression scores on the Beck Depression Inventory II 2. To compare the efficacy of treatment with 2 dosages of bicifadine SR with placebo on the following health outcome measures: • change from Baseline in daily functioning as measured by the interference portion of the BPI • change from Baseline in quality of life as measured by the Short Form-36 version 2 Health Survey (SF-36v2);Primary end point(s): The primary efficacy measure is the PI-NRS, which is a 0-10 rating of average pain intensity over a 24-hour period. Subjects make these ratings each day in an electronic diary. The primary efficacy variable is the change from Baseline to Week 14 in the weekly mean of the PI-NRS scores. Secondary efficacy measures of the BPI, SF-MPQ, and BDI are all analyzed as change scores from Baseline to Weeks 6, 10, and 14. CGI-I and PGIC scores are analyzed as raw scores at Weeks 6, 10, and 14. The he | — |
Countries
Germany
Outcome results
None listed