A Phase IIa, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Efficacy of DA-9805 in Subjects With Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Change in Motor MDS-UPDRS Score From Baseline at Week 12
研究概览
简要总结
This is a phase IIa, first in human, randomized, double-blind, multicenter study to evaluate the safety, tolerability and efficacy of DA-9805 at 45mg, 90mg versus placebo in subjects diagnosed with early Parkinson's disease.
详细描述
Parkinson's disease (PD) is recognized as one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. There are 2 major neuropathologic findings: the loss of pigmented dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies.
Parkinson's disease affects an estimated 1.5 million persons in the United States, with over ten million affected worldwide, and these estimates are expected to increase substantially in the next few decades. Despite the increasing prevalence, the approved agents for the early management of Parkinson's disease have changed little in the past decade; however, there have been advances in drug delivery, dosing, and the use of combination therapy in an attempt to reduce adverse events. The most important, unmet medical need in targeting Parkinson's disease is developing agents with neuroprotective potential. So far, no drug has been shown to reduce or slow down the progression of PD.
DA-9805 is a botanical drug product composed of three main raw herbal materials. It is expected that DA-9805 will help treat PD by prevention of dopaminergic neurodegeneration via recovery of mitochondrial dysfunction, anti-inflammatory effect and relief from Endoplasmic reticulum (ER) stress and oxidative stress.
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
- 30 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects who are between 30 and 79 years old inclusive with a clinical diagnosis of Parkinson's disease as per UK Brain Bank Criteria for two (2) years or less at screening.
- •Hoehn and Yahr I or II at screening.
- •Subjects who are newly diagnosed & currently not on any Parkinson's disease medication (or) subjects who are on stable doses for at least 4 weeks prior to screening on Amantadine or anticholinergics for treatment of Parkinson's disease
- •*Note: Subjects that had anti-parkinsonian medication (including levodopa, dopamine agonists, entacapone and monoamine oxidase-B inhibitors) discontinued at least 60 days prior to screening, e.g., for intolerance, may be considered eligible if all other eligibility requirements are met.
- •Women of child-bearing potential should use reliable contraception. Acceptable methods of contraception include: surgical sterilization (e.g. bilateral tubal ligation), hormonal contraception (implantable, patch, and oral), and double-barrier methods (condom, diaphragm and spermicide are each considered a barrier). Women of child-bearing potential are defined as women physiologically capable of becoming pregnant, UNLESS they meet the following criteria:
- •(1)Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40mIU/m, OR; (2)6 weeks post surgical bilateral oophorectomy with or without hysterectomy
- •If a male and heterosexually active with a female of childbearing potential, the subject must agree to use a double barrier method of birth control (or must have been surgically sterilized) and to not donate sperm during the study.
- •Without clinically significant abnormalities in physical exam, neurological exam and laboratory assessments (urine/blood routine, biochemical tests and ECG) which would exclude the subject from the study in the opinion of the Investigator. For Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) the screening levels should be ≤ 2 times upper limit normal
- •Subject is capable of providing informed consent and is willing to sign the ICF prior to study Screening and agrees to comply with the study protocol requirements.
排除标准
- •Subject has an atypical parkinsonian syndrome or secondary parkinsonism (e.g., due to drugs, metabolic neurogenetic disorders, encephalitis, cerebrovascular disease or degenerative disease).
- •Subjects with history of neurosurgical intervention for Parkinson's disease.
- •Subjects who meet the DSM-V criteria at screening for bipolar disorder, major depressive disorder, psychotic disorders, or any other comorbid mental disorders that in the opinion of the Investigator may interfere with study conduct and results interpretation.
- •Subjects with clinical diagnosis of dementia (MMSE score <24) as determined by the investigator using Mini-Mental State Examination (MMSE).
- •Female subjects who are pregnant or breast feeding.
- •Initiation of any anti-parkinsonian medication (including levodopa, dopamine agonists, entacapone and monoamine oxidase-B inhibitors) for the duration of the trial.
- •Initiation of Amantadine or anticholinergics for newly diagnosed subjects or change in the dosage of Amantadine or anticholinergics during the trial for subjects who were on stable doses for 4 weeks prior to screening.
- •Subjects who used investigational drugs or devices within 60 days prior to screening or investigational biologics within the last 6 months prior to screening.
- •Subjects with a clinically significant or surgical condition, including major surgeries within 28 days prior to enrollment
研究组 & 干预措施
DA-9805 high
DA-9805 90mg
干预措施: DA-9805 90mg (Drug)
Placebo
placebo, tid
干预措施: Placebo (Other)
DA-9805 low
DA-9805 45mg
干预措施: DA-9805 45mg (Drug)
结局指标
主要结局
Change in Motor MDS-UPDRS Score From Baseline at Week 12
时间窗: 12 weeks
Analysis of the Change from Baseline in the sum of the Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part II, Part III and Part IV at week 12. (Change from baseline = Post Baseline Measurement - Baseline Measurement) MDS-UPDRS is a multimodal scale assessing both impairment and disability and is separated into 4 subscales. Each parkinsonian sign or symptom is rated on a 5-point severity scale (ranging from 0 to 4). The maximum total UPDRS score is 272, indicating the worst possible disability from PD. Part I: This assesses non-motor experiences of daily living (13 items, Score range: 0\~52) Part II: This assesses motor experiences of daily living (13 items, Score range: 0\~52) Part III: This assesses the motor signs of PD (33 items, Score range: 0\~132) Part IV: This assesses motor complications, dyskinesias and motor fluctuations using historical and objective information (6 items, Score range: 0\~26)
次要结局
- Change in Total MDS- UPDRS Score(12 weeks)
- Change in MDS-UPDRS Subscale scores_Part II(12 weeks)
- Change in Clinical Global Impression-Severity (CGI-S)(12 weeks)
- Scores of Clinical Global Impression-Improvement (CGI-I)(12 weeks)
- Change in MDS-UPDRS Subscale scores_Part I(12 weeks)
- Change in MDS-UPDRS Subscale scores_Part III(12 weeks)
- Change in MDS-UPDRS Subscale scores_Part IV(12 weeks)
- Change in S&E Total Score(12 weeks)
- Change in PDQ-39 Score- Summary Index(12 weeks)
- Change in H&Y Total Score at Week 12(12 weeks)