Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: IV to IM Bridging Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Safety - clinical laboratory measures
研究概览
简要总结
The purpose of this study is to identifying the intramuscular dose equivalent to the 4mg intravenous dose and assess its safety and tolerability as a weekly injection.
详细描述
The purpose of this bridging study is to advance the therapeutic development of Allopregnanolone (Allo) by using the intramuscular (IM) route of administration as an alternative to the intravenous (IV) route. In order to identify the equivalent IM dose we will conduct pharmacokinetic (PK) analysis previously informed by simulations and modeling. We will recruit a total of 12 participants, both males and females equally distributed, into this single-arm, open-label study.
PK analysis and dose finding will take place for the initial 4 weeks; some participants may not require all 4 weeks of initial dosing to establish maintenance dose. Once maintenance dose is established all participants will receive weekly administration of Allo IM until they complete 12 weeks total of Allo exposure (5 or 6 clinic visits and 6 or 7 home-nurse visits).
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
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Men or postmenopausal women, aged 55 years or older
- •Diagnosis of MCI due to AD or mild AD
- •In good general health as evidenced by medical history and with no medical contraindications to participation
- •MMSE > 20 at screen
- •Caregiver willing and capable to accompany the patient to clinic visits
排除标准
- •Daily use of benzodiazepines, sedative/hypnotics, anticonvulsants, antipsychotics, and other drugs that might interact with the GABA-A receptor complex.
- •Seizure disorder, history of stroke, focal brain lesion, traumatic brain injury, substance abuse, malignancy.
- •Clinically significant laboratory or ECG abnormality obtained at screening visit.
- •MRI indicative of significant abnormality, including but not limited to evidence of a single prior hemorrhage or infarct >1 cm3, multiple lacunar infarcts (>1) or evidence of a single prior infarct >1cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (e.g. abscess or tumor).
- •Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI.
- •Is currently enrolled in a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research or observational study judged not to be scientifically or medically compatible with this study.
研究组 & 干预措施
Allo IM cohort
Allopregnanolone 4-18mg IM, weekly, for 12 weeks.
干预措施: Allopregnanolone (Drug)
结局指标
主要结局
Safety - clinical laboratory measures
时间窗: From Baseline to visit 16 (14 weeks)
Proportion of subjects exceeding pre-established critical laboratory values.
Safety - clinical assessment
时间窗: From Baseline to visit 16 (14 weeks)
Proportion of subjects with abnormal findings in physical/neurological exams, vital signs and electrocardiograms.
Safety - Adverse events
时间窗: From baseline to visit 16 (14 weeks)
Incidence and severity of treatment emergent adverse events assessed weekly.
次要结局
- Pharmacokinetic parameter - Volume of distribution(Visits 3 - 6 (up to 4 weeks))
- Satisfaction and feasibility of home nurse survey(Visits 8-9 and 11-15 (up to 8 weeks))
- Pharmacokinetic parameter - Cmax(Visits 3 - 6 (up to 4 weeks))
- Pharmacokinetic parameter - Tmax(Visits 3 - 6 (up to 4 weeks))
- Pharmacokinetic parameter - Clearance(Visits 3 - 6 (up to 4 weeks))
- Pharmacokinetic parameter - AUC(Visits 3 - 6 (up to 4 weeks))
研究者
Roberta Brinton
Professor
University of Arizona