A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Number of patients experiencing drug limiting toxicity (DLT),
研究概览
简要总结
This is a multi-center, open label, pilot futility clinical trial of the safety, tolerability, pharmacodynamics and preliminary efficacy of oral salsalate in up to 10 patients with PSP.
详细描述
This is a multi-center, open label, pilot futility clinical trial of the safety, tolerability, pharmacodynamics and preliminary efficacy of oral salsalate in up to 10 patients with PSP. All participants will be administered 2,250 mg daily [1,500 mg every day before noon (every AM) and 750 mg every night at bedtime (every HS)] for 6 months.
If ≥3 patients experience drug limiting toxicity (DLT), as defined below, the study will be terminated.
A DLT is defined as: 1) any Grade 3 or higher adverse event (AE) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for which there is reasonable possibility that salsalate caused the event, 2) any Grade 2 AE in the CTCAE system organ class of nervous system disorders that is considered clinically significant and for which there is reasonable possibility that salsalate caused the event, or 3) any Grade 2 or higher treatment-related adverse events during administration that do not resolve promptly with supportive treatment.
An interim futility analysis will be performed after five subjects have completed 6 months of study drug treatment. If the criteria listed in the Statistical Methods section of this synopsis are met, an additional 5 subjects will be enrolled in the trial. If not, the trial will be terminated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria,(Litvan 1996a) as modified from the AL-108-231 trial.(Boxer 2014)
- •Agrees to 3 magnetic resonance imaging (MRI) or subject to investigator's discretion
- •MRI at screening is consistent with PSP (≤4 microhemorrhages and no large strokes or severe white matter disease)
- •Mini-Mental State Examination (MMSE) score 14-30
- •Stable medications for 2 months prior to screening, including FDA approved Alzheimer's disease (AD) medications and Parkinson's disease medications
- •Availability of a study partner who knows the patient well and is willing to accompany the patient to all trial visits and to participate in questionnaires
- •Agrees to 2 lumbar punctures for cerebrospinal fluid (CSF) examination
- •Signed and dated written informed consent obtained from the subject and subject's caregiver in accordance with local IRB regulations
- •Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.
- •Adequate contraceptive methods include those with a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as complete abstinence from sexual intercourse with a potentially fertile partner, and some double barrier methods condom with spermicide) in conjunction with use by the partner of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, birth control patch or vaginal ring, oral, or injectable or implanted contraceptives.
- •For this study, a woman who has been surgically sterilized or who has been in a state of amenorrhea for more than two years will be deemed not to be of childbearing potential;
排除标准
- •Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD (McKhann et al. 2011);
- •Any medical condition other than PSP that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
- •A prominent and sustained response to levodopa therapy;
- •History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
- •History of hypertension (repeated elevations in blood pressure exceeding 180 mm Hg systolic or 100 mm Hg diastolic; medical intervention indicated);
- •History of severe gastrointestinal bleed, or gastric or peptic ulcers;
- •History of aspirin triad (i.e., aspirin allergy, nasal polyps and asthma) or asthma;
- •History of major psychiatric illness or untreated depression;
- •Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x ULN, aspartate aminotransferase (AST) >3 x ULN, or INR >1.2 at Screening evaluations;
- •Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;
- •Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
- •Current clinically significant viral infection. Subjects with chicken pox, influenza, or flu symptoms are not eligible;
- •Major surgery within four weeks prior to Screening;
- •Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening;
- •Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;
- •Chronic use of other NSAIDs or salicylates for any reason, except for daily baby aspirin (81 mg);
- •Concurrent treatment with thiazides or loop diuretics;
- •Concurrent use of oral corticosteroids or angiotensin-converting enzyme (ACE) inhibitors;
- •Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to Screening or during the trial;
- •Known hypersensitivity to the inactive ingredients in the study drug;
- •Pregnant or lactating;
- •Positive pregnancy test at Screening or Baseline (Day 1);
- •Cancer within 5 years of Screening, except for non-metastatic skin cancer or nonmetastatic prostate cancer not expected to cause significant morbidity or mortality within one year of Baseline.
研究组 & 干预措施
Salsalate
All participants will be administered 2,250 mg daily [1,500 mg every day before noon (every AM) and 750 mg every night at bedtime (every HS)] for 6 months.
干预措施: Salsalate (Drug)
结局指标
主要结局
Number of patients experiencing drug limiting toxicity (DLT),
时间窗: 6 months
defined as: 1) any Grade 3 or higher adverse event (AE) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for which there is reasonable possibility that salsalate caused the event, 2) any Grade 2 AE in the CTCAE system organ class of nervous system disorders that is considered clinically significant and for which there is reasonable possibility that salsalate caused the event, or 3) any Grade 2 or higher treatment-related adverse events during administration that do not resolve promptly with supportive treatment.
次要结局
- Changes in behavior(6 months)
- Changes in activities of daily living(6 months)
- Changes in motor function(6 months)
- Changes in cognition(6 months)
研究者
Adam Boxer
MD, PhD
University of California, San Francisco