NCT01963208已完成3 期
A Multicenter, Double Blind, Randomized, Placebo-Controlled Trial to Determine the Efficacy and Safety of Ganaxolone as Adjunctive Therapy for Adults With Drug-Resistant Partial-Onset Seizures Followed by Long-term Open-Label Treatment
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 405
- 试验地点
- 60
- 主要终点
- Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
研究概览
简要总结
The study will evaluate the effectiveness and safety of an investigational drug-ganaxolone - on partial seizure frequency in adults with epilepsy taking a maximum of 3 antiepileptic medications (AEDs).
详细描述
This is a 2-cohort study comprised of 2 phases in each cohort. Phase 1 is a double-blind (DB) phase followed by Phase 2, an open-label phase. Cohort 1 will provide tolerability, safety, and PK information for ganaxolone 1200 milligram per day (mg/day), 1800 mg/day and placebo. Cohort 2 will investigate the efficacy, tolerability and safety of ganaxolone 1800 mg/day compared to placebo. Cohort 1 (N= approximately 50) will enroll into a 67-week study comprised of a 4-week prospective baseline period plus 4 week retrospective baseline followed by two treatment phases: a 9-week randomized DB placebo-controlled treatment phase followed by a 52-week open label treatment phase. Cohort 2 (N=150) will enroll into a 72-week study comprised of a 8-week prospective baseline period followed by two treatment phases: a 14-week randomized DB placebo-controlled treatment phase followed by a 52-week open label treatment phase.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to give informed consent in writing, or have a legally authorized representative able to do so
- •Willing to enter and participate for the full term of the double blind phase and willing to enter into the open-label phase
- •Male or female outpatients > 18 years of age
- •Have a confident diagnosis of drug-resistant epilepsy with partial-onset seizures (POS), with or without secondary generalization, for ≥2 years. Have residual POS despite having been treated in the past with at least 2 approved anti-epilepsy drugs (AEDs) either alone or in combination
- •Based on history, participants would be anticipated to have at least 3 POS during each 4-week Baseline period and unlikely to have 21 or more consecutive POS-free days
- •Currently being treated and maintained with a stable regimen of 1, 2, or 3 AEDs
- •Able and willing to maintain daily seizure calendar
- •Able and willing to take drug with food twice daily
- •Sexually active women of childbearing potential must use acceptable birth control and have a negative pregnancy test at all visits
排除标准
- •Have had previous exposure to ganaxolone
- •Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds
- •Exposure to any investigational drug or device <30 days prior to screening, or plans to take another investigational drug at any time during the study
- •Time of onset of epilepsy treatment <2 years prior to enrollment
- •Have generalized epilepsy, such as Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, absence epilepsy, or non-epileptic seizures within the last 12- month period prior to study entry
- •Have less than 3 POS seizures in a 28-day period or more than 21 consecutive seizure-free days during the Baseline period
- •Have only simple partial seizures without any observable motor component
- •Have innumerable seizures or status epilepticus within the last 12-months prior to screening
- •Have more than 100 POS per 4-week Baseline period
- •Have seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease
- •Current use of vigabatrin is not permitted. If prior use of vigabatrin, must have documented stable visual fields
- •Current use of ezogabine is not permitted. If prior use, must have been off the medication for at least 3 months prior to screening and have had documented normal fundoscopic exam by ophthalmologist
- •Are planning surgery, or to be evaluated for surgery, during the double-blind phase to control seizures including VNS implantation
- •Are suffering from acute or progressive neurological disease, moderate or severe psychiatric disease, or severe mental abnormalities that are likely to require changes in drug therapy during the double-blind portion of the study or interfere with the objectives of the study or the ability to adhere to the protocol requirements
- •Have a history of an actual suicide attempt in the last 5 years or more than 1 lifetime suicide attempt
- •Have a positive urine drug screen at Screening or meet criteria for current or historical Substance Use Disorder (DSM-V criteria) within the past 5 years.
- •Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect participant safety or study outcome, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs
- •Have elevated ALT (SGPT) or AST (SGOT) greater than 3 times upper limits of normal, or total bilirubin greater than 1.5 times ULN
- •Have a history of malignancy within the past 2 years, with the exception of basal cell carcinoma
- •Are currently following or planning to follow a ketogenic diet
- •Use of dietary supplements or herbal preparations are not permitted if participant has been using them consistently for less than 6 months prior to screening, or does not plan on remaining on stable doses for the duration of the double blind phase. Use of St. John's Wort is not permitted
- •Females who are pregnant, currently breastfeeding or planning to become pregnant during the duration of the study
- •A history of chronic noncompliance with drug regimens
- •Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial
研究组 & 干预措施
Double Blind - Cohort 2 - Placebo
Placebo Comparator
Placebo +AED
干预措施: Placebo (Drug)
Open Label - Placebo in Double-blind phase
Experimental
1800 mg/day + AED
干预措施: ganaxolone (Drug)
Double Blind - Cohort 1 - Ganaxolone
Experimental
1200 mg/day and 1800 mg/day + AED
干预措施: ganaxolone (Drug)
Double Blind - Cohort 1 - Placebo
Placebo Comparator
Placebo + AED
干预措施: Placebo (Drug)
Open Label - Ganaxolone in Double-blind phase
Experimental
1800 mg/day + AED
干预措施: ganaxolone (Drug)
Double Blind - Cohort 2 - Ganaxolone
Experimental
1800 mg/day + AED
干预措施: ganaxolone (Drug)
结局指标
主要结局
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
时间窗: Baseline and Week 14
Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. Primary analysis was performed using a rank analysis of covariance (ANCOVA).
次要结局
- Double Blind: Cohort 2: Number of Participants With ≥50% Responder Rate During Titration + Maintenance Period(Up to Week 14)
- Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period(Baseline and Week 14)
- Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14(At Week 14)
- Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period(Baseline and Week 2 to Week 14)
- Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period(Baseline and Week 14)
- Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Maintenance Period(Baseline and Week 2 to Week 14)
- Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Maintenance Period(Baseline and Week 2 to Week 14)
- Double Blind: Cohort 2: Percentage of Responders Experiencing a ≥R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Titration + Maintenance Period(Up to Week 14)
- Double Blind: Cohort 2: Percentage of Responders Experiencing a ≥R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Maintenance Period(Week 2 to Week 14)
- Double Blind: Cohort 2: Percentage of Seizure Free Participants During the Maintenance Period(Week 2 to Week 14)
- Double Blind: Cohort 2: Percentage of Participants Who Experienced at Least One 28-day Seizure Free Period During Titration + Maintenance Phase(Up to Week 14)
- Double Blind: Cohort 2: Longest Percent of Time Spent Seizure-free During Titration + Maintenance Period(Up to Week 14)
- Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency for Different Subtypes of Seizures During Titration + Maintenance Period(Baseline and Week 14)
- Double Blind: Cohort 2: Number of Participants With Patient Global Impression of Change - Improvement (PGI-I) at Week 8 and Week 14(Week 8 and Week 14)
- Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 8(At Week 8)
研究者
研究点 (60)
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