A Phase IIa Placebo-Controlled, Double-Blind Randomized Withdrawal Study to Evaluate the Safety and Efficacy of CNV1014802 in Patients With Trigeminal Neuralgia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- The number of failures on CNV1014802 vs. number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
研究概览
简要总结
This is a double-blind, randomized withdrawal study comparing CNV1014802 with placebo in patients with trigeminal neuralgia who have successfully responded to CNV1014802 in an initial open-label phase.
Patients will participate in an initial open-label treatment period of 21 days of CNV1014802 150mg three times a day (tid). Responders will be randomized to 28 days of CNV1014802 150mg tid or placebo.
Following an interim analysis after 10 evaluable patients have completed the open-label phase, the dose regimen may be increased to 350mg twice a day (bid) for the remainder of the trial if the responder rate is less than 60%.
详细描述
In order to be randomised and enter the double-blind placebo controlled phase of the study, patients must satisfy at least one of the following criteria:
- 30% or more decrease in number of paroxysms (either spontaneous, evoked, or both)
- 30% reduction in the severity of pain experienced during the paroxysm (either spontaneous, evoked or both)
- A Patient Global Improvement of Change rating of much improved/very much improved The response will be compared with the baseline recordings of pain made in the 7 day run-in period. If a patient meets one of these criteria they are termed a responder, and will be eligible to be randomized into the double-blind treatment phase.
During the double-blind randomised phase, patients will be evaluated to determine if they meet the failure criteria at each clinic visit which will occur every 7 days in the double-blind treatment period. The number of failures on CNV1014802 versus number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
Patients will be classified as a treatment failure if they meet one of the following criteria:
- 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period
- 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period
- A Patient Global Improvement of Change rating of much worse/very much worse
- The patient discontinues the study due to 'Lack of Efficacy'
- The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged between 18 and 70 years, with a diagnosis of trigeminal neuralgia; IHS criteria to be used.
- •Female patients must be of non-child bearing potential or agree to use an approved form of contraception
- •Male patients must agree to use an approved form of contraception
- •Body weight > 50 kg for men and > 45 kg for women.
- •BMI ≤ 34.9
- •Capable of giving written informed consent. Informed consent must be obtained prior to the commencement of any study related procedures.
- •QTcB either/or QTcF < 450 msec in two of three ECGs conducted at screening
- •AST and ALT < 2xULN; alkaline phosphatase and bilirubin < 1.5xULN.
- •Approved concomitant medications must have been stable for at least 3 weeks prior to day 0.
排除标准
- •Patients who are known non-responders to sodium channel blockers at therapeutic doses.
- •Patients with causes for their facial pain other than that specified in Inclusion Criterion
- •A positive pre-study drug screen.
- •A positive history of HIV.
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- •History of any liver disease within the last 6 months, with the exception of known Gilbert's disease.
- •History of excessive regular alcohol consumption within 6 months of the study.
- •Patients with a history or risk of seizures or a history of epilepsy, head injury or related neurological disorders
- •Patients with a history of uncontrolled or poorly controlled hypertension, with systolic BP frequently exceeding 160mmHg and/or diastolic BP frequently exceeding 100mmHg, or patients who have BP greater than or equal to 160mmHg systolic and/or greater than or equal to 100mmHg diastolic at screening after repeated measurements
- •History or presence of significant cardiovascular, gastro-intestinal, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •Patients with conditions known to affect cardiac conduction or a personal or familial history of Brugada syndrome
- •Pregnant females or lactating females.
- •History or presence of any clinically significant abnormality in vital signs/ECG/laboratory tests or have any medical or psychiatric condition, which, in the opinion of the Investigator may interfere with the study procedures or compromise patient safety.
- •History of suicidal ideation and/or suicide attempts or clinical evidence of recent major depression.
- •Patients who are unable to maintain approved medications for their trigeminal neuralgia at a stable dose during the study.
- •Unable to refrain from excessive use of sedatives.
- •Unable to comply with the prohibited concomitant medication restrictions as detailed in the protocol. This includes but is not limited to sodium channel blockers or drugs that adversely interact with a monoamine oxidase-B inhibitor: MAOI's, antidepressants, opioids and sympathomimetic agents.
- •History of hypersensitivity to CNV
- •The patient has participated in a clinical trial and has received an investigational product within 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to the start of this study.
- •Exposure to more than four new chemical entities (medications for which no marketing authorization has been obtained) within 12 months prior to the first dosing day.
- •Where participation in the study would result in total donation of blood or blood products in excess of 500mL within a 56 day period.
- •Patient is mentally or legally incapacitated.
- •Unwillingness or inability to follow the procedures outlined in the protocol.
研究组 & 干预措施
CNV1014802
干预措施: CNV1014802 (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The number of failures on CNV1014802 vs. number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
时间窗: 4 weeks
Patients will be classified as a treatment failure if they meet one of the following criteria: * 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period * 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period * A Patient Global Improvement of Change rating of much worse/very much worse * The patient discontinues the study due to 'Lack of Efficacy'. v. The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication
次要结局
- Secondary pain endpoints(4 weeks)