Diabetic Peripheral Neuropathic Pain (DPNP) MedDRA version: 9.1 Level: LLT Classification code 10012683 Term: Diabetic peripheral neuropathy
Conditions
Sponsors
Vernalis (R & D) Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent 2) Male or female 18 – 75 years of age 3) Diagnosis of diabetes mellitus (Type I or II) 4) No change in diabetes medications within 4 weeks before screening 5) Daily pain attributed to diabetic neuropathy present for at least 6 months immediately prior to study entry 6) Presents with pain due to bilateral peripheral neuropathy caused by Type I or Type II diabetes mellitus. Pain must have begun in the feet, with relatively symmetrical onset. The diagnosis must be confirmed by a score of at least 2 on Section B (Physical Assessment) of the Michigan Neuropathy Screening Instrument (MNSI) 7) Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol 8) Females should be of non child-bearing potential (i.e., surgically sterilized or at least 1 year post-menopause). Male subjects who are sexually active with a female partner of child bearing potential must agree to use a barrier method of contraception (eg condom, diaphragm or cervical cap in the female partner) for the duration of the study (until the follow up visit). Final Inclusion Criteria Before patients are randomised to double-blind study drug treatment, the following additional inclusion criteria fulfillment must be established at the baseline visit: 9) A mean average pain intensity of at least 4, but less than or equal to 9, on an 11 point Likert NPRS recorded twice daily (in the morning and evening) during the two week placebo run-in before randomisation (baseline); however, any patient who experiences a >30% decrease in the mean pain score compared to Day -16 (Screening) score, during placebo run-in will be excluded, regardless of whether their final score is greater than or equal to 4 10) Full completion of the daily diaries for at least 11 of the placebo run-in days. 11) Compliance in taking study medication twice daily for at least 11 of the placebo run-in days 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) Any clinically significant neurologic disorders (with the exception of diabetic peripheral neuropathic pain) 2) Any clinically significant or unstable medical or psychiatric condition that would interfere with the patient’s ability to participate in the study 3) Prior renal transplant, current renal dialysis 4) Pernicious anemia 5) Untreated hypothyroidism 6) Amputations or persistent ulceration due to diabetes mellitus 7) Any cardiovascular condition that would be a contraindication to the use of sympathomimetic amines (e.g., active angina) 8) Uncontrolled hypertension (i.e., >140/90 mm Hg despite adequate medical therapy) 9) Known or at high risk of human immunodeficiency virus (HIV) infection 10) Any anticipated need for surgery during the study 11) Increased risk of seizures (defined as a history of seizure disorder (including alcoholic seizures), family history of seizures and history of head trauma that resulted in loss of consciousness or concussion). 12) Any malignancy in the past 2 years (with the exception of basal cell carcinoma) 13) Pain that cannot be clearly differentiated from, or conditions that interfere with, the assessment of diabetic neuropathic pain. Examples of painful conditions that could be confused with diabetic neuropathic pain include: 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); other painful conditions (e.g., arthritis) 14) Use of anticonvulsants, antidepressants (particularly MAO inhibitors), or prescription membrane-stabilizing agents, including topical therapies. Patients currently taking drugs in these classes may have them discontinued prior to entry into the placebo run-in period. Selective serotonin reuptake inhibitors should be discontinued at least 4 weeks prior to the run-in period; all other prohibited medications should be discontinued 2 weeks prior to run-in. 15) Use of opioids, especially meperidine (pethidine) 16) History of substance abuse or dependence within the past year, excluding nicotine and caffeine 17) Frequent and/or severe allergic reactions with multiple medications 18) Historical exposure to drugs known to cause neuropathy (for example, vincristine), or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy 19) Patients taking excluded medications that cannot be stopped at the baseline visit 20) Participation in any clinical trial within 30 days before screening Final Exclusion Criteria Before patients are randomised to double-blind study drug treatment, the following additional exclusion criteria fulfillment must be established at the baseline visit: 21) A score of 20 or more on the Beck Depression Inventory-II 22) Glycosylated haemoglobin (HbA1c) >11.0% 23) Serum creatinine laboratory value greater than 1.5 x upper limit of normal (ULN) reference range (after adjustment for age) or estimated creatinine clearance 1.5 times upper limit of normal reference ranges (after adjustment for age) 25) Any clinically significant abnormal laboratory test result(s) that would jeopardize the patient’s capacity to undergo investigative study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary safety objective of the study is to investigate the safety and tolerability of V3381 in patients with diabetic peripheral neuropathic pain at doses of up to 400 mg bid. The primary efficacy objective of the study is to determine the efficacy of V3381 in the treatment of diabetic peripheral neuropathic pain at doses of up to 400 mg bid. ;Secondary Objective: ;Primary end point(s): a) Primary safety endpoint: safety of V3381 compared to placebo determined by clinical assessment, AEs, vital signs, ECG, safety laboratory tests and Beck Depression Inventory II. b) Primary efficacy endpoint: Change from baseline in the mean average pain severity score from the diary entries for the last week of the 13-week study drug treatment period. | — |
Countries
Czech Republic, United Kingdom
Outcome results
None listed