A Phase 2a, Open-label, Multiple Dose, Safety, Pharmacokinetic and Biomarker Study of PTl-125 in Mild-to-moderate Alzheimer's Disease Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Plasma Half-life (T1/2)
研究概览
简要总结
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients.
详细描述
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate AD patients, 50-85 years of age. A total of twelve (12) patients will be enrolled into the study. Patients will receive 100 mg b.i.d. of PTI-125. The objectives of this study are to investigate the safety, pharmacokinetics and effect on biomarkers of PTI-125 following 28-day repeat-dose oral administration.
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
- •Ages >= 50 and <= 85 years
- •Informed consent form (ICF) signed by the subject or legally acceptable representative.
- •Clinical diagnosis of dementia due to possible or probable Alzheimer's disease
- •Mini-Mental State Examination score >= 16 and <= 24 at screening
- •If female, postmenopausal for at least 1 year
- •Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-hour) nursing care
- •General health status acceptable for participation in the study
- •Fluency (oral and written) in English or Spanish
- •If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months (90 days) before screening and with continuous dosing for at least 3 months. If receiving donepezil, receiving any dose lower than 23 mg once daily.
- •The patient is a non-smoker for at least 12 months.
- •The patient or legal representative must agree to comply with the drawing of blood samples and with a lumbar puncture and the drawing of cerebrospinal fluid samples.
- •The patient has a ratio of total tau/Abeta42 in cerebrospinal fluid >= 0.
- •Patient has a caregiver or legal representative responsible for administering the drug and recording the time.
排除标准
- •Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
- •Residence in a skilled nursing facility
- •Clinically significant laboratory test results
- •Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)
- •Insufficiently controlled diabetes mellitus or requiring insulin
- •Renal insufficiency (serum creatinine >2.0 mg/dL)
- •Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)
- •History of ischemic colitis or ischemic enterocolitis
- •Unstable medical condition that is clinically significant in the judgment of the investigator
- •Alanine transaminase (ALT) or aspartate transaminase (AST) >2 times the upper limit of normal or total bilirubin greater than the upper limit of normal.
- •History of myocardial infarction or unstable angina within 6 months before screening
- •History of more than 1 myocardial infarction within 5 years before screening
- •Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
- •Symptomatic hypotension, or uncontrolled hypertension
- •Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT value >= 450 msec for males or >= 470 msec for females.
- •Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
- •History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
- •Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
- •Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
- •Specific degenerative CNS disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
- •Wernicke's encephalopathy
- •Active acute or chronic Central Nervous System infection
- •Donepezil 23 mg or greater quaque die currently or within 3 months prior to enrollment in the study
- •Discontinued AChEI < 30 days prior to enrollment in the study
- •Antipsychotics; low doses are allowed only if given for sleep disturbances, agitation and/or aggression, and only if the subject has received a stable dose for at least 3 months before enrollment in the study
- •Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants are allowed only if the subject has received a stable dose for at least 3 months before enrollment in the study
- •Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed only if given for insomnia/sleep disturbance, and only if the subject has received a stable dose for at least 3 months before enrollment in the study
- •Peripherally acting drugs with effects on cholinergic transmission
- •Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)
- •Antiepileptic medications if taken for control of seizures
- •Chronic intake of opioid-containing analgesics
- •Sedating H1 antihistamines
- •Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
- •Clinically significant illness within 30 days of enrollment
- •History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
- •Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test at screening
- •Positive HIV test at screening
- •Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
- •Metformin or cimetidine.
研究组 & 干预措施
Simufilam (PTI-125)
Simufilam (PTI-125) 100 mg oral tablets administered twice daily (BID)
干预措施: PTI-125, 100 mg tablets (Drug)
结局指标
主要结局
Plasma Half-life (T1/2)
时间窗: Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose
Assessment of the half-life in plasma of PTI-125
Time to Last Quantifiable Plasma Concentration (Tlast)
时间窗: Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose
Levels of PTI-125 will be assessed to determine the elapsed time to where PTI-125 can last be detected in the plasma.
Time to Maximum Plasma Concentration (Tmax)
时间窗: Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose
Levels of PTI-125 will be assessed to determine how long it takes to reach the Cmax
Maximum Plasma Concentration (Cmax)
时间窗: Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose
Blood draws will be done to evaluate levels of PTI-125 in the plasma using non-compartmental methods in WinNonlin.
Last Quantifiable Plasma Concentration (Clast)
时间窗: Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose
Levels of PTI-125 will be assessed to determine the last time point where PTI-125 can be detected.
Area Under the Curve (AUClast)
时间窗: Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose
AUC for PTI-125 plasma concentration from time zero to the last quantifiable plasma concentration.
次要结局
- CSF Biomarkers(Change from Baseline to Day 28)
- SavaDx (Biomarker)(Study Day 1 and Day 28)