A Randomised, Double-blind, Placebo-controlled, Multicentre, Parallel Group Study of the Safety, Tolerability and Efficacy of V3381 for up to 13 Weeks in Patients With Diabetic Peripheral Neuropathic Pain (DPNP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 161
- 试验地点
- 27
- 主要终点
- Investigate the safety and tolerability of V3381 in patients with diabetic neuropathic pain at doses of up to 400 mg bid
研究概览
简要总结
Randomised, double-blind, placebo-controlled, parallel group, multicentre study of oral doses of V3381, titrated to effect. A 2-week single-blind run-in period will be followed by a 13 week double-blind titration and maintenance phase. Doses will be titrated up in 100 mg bid increments every one or two weeks, starting from 100 mg bid. A 2 week follow-up period will conclude patient participation in the study.
详细描述
Patients who provide written informed consent will be screened for entry into the study.
Patients will initially enter a 2-week single-blind run-in phase, during which they will complete an 11 point numerical pain rating scale (NPRS) on their average daily pain; patients with a mean weekly score of >4 and <9 will be allowed to continue in the study to randomisation (unless they have exhibited a >50% decrease in pain score, compared to the Day -14 score, during the run-in).
Patients will be randomised to receive either Placebo (PL) bid (n=75) or V3381 (n=75) and will initially be treated with 100 mg V3381 (or placebo equivalent) twice daily (bid) for one week. Patients will remain on the same study treatment throughout the trial. At the end of one week those patients who adequately tolerated study medication will escalate the dose of V3381 to 200 mg bid on a blinded basis. Patients who do not tolerate 100 mg bid will be withdrawn.
After one week of treatment at the 200 mg bid dose level, those subjects who continue to tolerate adequately 200 mg bid study drug will escalate to 300 mg bid. Subjects who have not tolerated the 200 mg bid dose may revert to the 100 mg bid dose and should remain at this dose level for the remainder of the trial.
After a further 2 weeks of treatment those subjects who continue to tolerate adequately 300 mg bid study drug will escalate to 400 mg bid. Subjects who have not tolerated the 300 mg bid dose may revert to the 200 mg bid dose and should remain at this dose level for the remainder of the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •Male or female aged 18 - 75 (18-65 Czech Republic)
- •Diagnosis of diabetes mellitus
- •No change in diabetes medications within 4 weeks before screening
- •Daily pain attributed to diabetic neuropathy present for at least 6 months immediately prior to study entry
- •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. Diagnosis confirmed by a score of at least 2 on Section B of the MNSI
- •Judged to be reliable and agree to keep all appointments required by the protocol
- •Females should be of non child-bearing potential (i.e. surgically sterilized or >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 female partner) for the duration of the study (until the follow up visit)
- •Additionally, at the baseline visit:
- •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 during the two week placebo run-in; any patient who experiences a >30% decrease in the mean pain score compared to Day -14 during placebo run-in will be excluded, regardless of whether their final score is >4
- •Full completion of daily diaries for at least 11 of the days up to Day -1
- •Compliance in taking placebo run-in medication twice daily for at least 11 of the days up to Day -1
排除标准
- •Any clinically significant neurologic disorders (except DPNP)
- •Any clinically significant or unstable medical or psychiatric condition that would affect the patient's ability to participate in the study
- •Prior renal transplant, current renal dialysis
- •Pernicious anemia
- •Untreated hypothyroidism
- •Amputations or persistent ulceration due to diabetes mellitus
- •Any cardiovascular condition that would contraindicate the use of sympathomimetic amines
- •Uncontrolled hypertension
- •Known or at high risk of HIV infection
- •Any anticipated need for surgery during the study
- •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).
- •Any malignancy in the past 2 years (except basal cell carcinoma)
- •Pain that cannot be clearly differentiated from, or conditions that interfere with, the assessment of diabetic neuropathic pain
- •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.
- •Use of opioids, especially meperidine (pethidine)
研究组 & 干预措施
V3381
V3381: titrated from 100 mg bid to maximum 400 mg bid over 4 weeks followed by maintenance phase at highest tolerated dose. Total duration of treatment 13 weeks.
干预措施: V3381 (Drug)
Placebo
Placebo to match V3381, 100 mg, given according to the same regimen.
干预措施: Placebo (Drug)
结局指标
主要结局
Investigate the safety and tolerability of V3381 in patients with diabetic neuropathic pain at doses of up to 400 mg bid
时间窗: 17 weeks
次要结局
- Determine the efficacy of V3381 in the treatment of diabetic peripheral neuropathic pain at does of up to 400 mg bid(17 weeks)