A Multicentre, Phase 3, Clinical Study to Compare the Striatal Uptake of a Dopamine Transporter Radioligand, DaTSCAN™ Ioflupane (123I) Injection, After Intravenous Administration to Chinese Patients With a Diagnosis of Parkinson's Disease, Multiple System Atrophy, Progressive Supranuclear Palsy, or Essential Tremor and to Healthy Controls
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 172
- 试验地点
- 10
- 主要终点
- Sensitivity Analysis of the Blinded Independent Read of DaTSCAN™ SPECT Images
研究概览
简要总结
This is a multicenter, open-label, non-controlled, non-randomized, phase 3 clinical study to compare the SPECT findings after a single IV administration of DaTSCAN™ ioflupane (123I) injection for patients with a clinical diagnosis of Parkinsonian syndrome (PS) involving striatal dopaminergic deficit (SDD; specifically, Parkinson's disease [PD] [SDD], multiple system atrophy [MSA] [SDD] or or progressive supranuclear palsy [PSP] [SDD]) as compared with patients with a clinical diagnosis of essential tremor (ET) (no SDD) and age-matched healthy controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For all participants:
- •Chinese male or female, aged 40 to 80 years, has agreed to sign and date the written informed consent form.
- •For Healthy Volunteers:
- •Non-patient volunteers with good age-appropriate health as established by clinical examination during screening and no evidence of movement disorder by complete neurological evaluation.
- •For participants with Parkinson's disease:
- •A diagnosis of clinically established or clinically probable PD in accordance with the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease.
- •For participants with MSA (SDD):
- •A diagnosis of probable or possible MSA in accordance with the Second Consensus Statement on the Diagnosis of MSA.
- •For participants with PSP (SDD):
- •A diagnosis of probable or possible PSP in accordance with the Clinical Criteria for the Diagnosis of Progressive Supranuclear Palsy National Institute for Neurological Disorders and Society for PSP (NINDS-SPSP)
- •For participants with ET (no SDD):
- •A diagnosis of definite or probable ET in accordance with the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) diagnostic criteria for ET (no SDD) .
排除标准
- •The participant is lactating.
- •The participant is pregnant as detected by a β-human chorionic gonadotropin (β-hCG) pregnancy test.
- •A cerebral structural vascular abnormality indicative of at least 1 infarction in the region of the basal ganglia (including the internal capsule) ≥5 mm has been confirmed, preferably by magnetic resonance imaging (MRI) performed within 6 months of screening. If an MRI is not clinically feasible, cerebral CT imaging within 6 months is also acceptable.
- •The participant is diagnosed with major neurocognitive disorder by the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria, or Mini-Mental State Examination total score is <
- •Participant is being investigated for or has been diagnosed and/or is being treated for repeated stroke with stepwise progression of Parkinson features.
- •History of repeated head injury (≥3 concussions, or history of professional sports with repeated head trauma [e.g., boxing]).
- •History of definite encephalitis (≥1 episode of confirmed encephalitis with objective residual neurologic deficit).
- •The participant is using or has insufficient washout from medication known or suspected to interact with striatal uptake through direct competition with binding of DaTSCAN™ to the dopamine transporters (i.e., amphetamine, benztropine, bupropion, cocaine, mazindol, methylphenidate, phentermine, sertraline, selective serotonin reuptake inhibitors) before the imaging visit.
- •The participant is using Chinese traditional medicine for PD treatment, which cannot be safely withdrawn for at least 1 week (7 days) before the imaging visit.
- •The participant has a moderate to severe renal impairment (e.g., serum creatinine >1.5x upper limit of normal [ULN], blood urea nitrogen [BUN] >30 mg/dL).
- •The participant has a moderate to severe hepatic impairment (bilirubin >2x ULN and alanine aminotransferase (ALT) or aspartate aminotransferase (AST)>3x ULN).
- •The participant has a history of current abuse of drugs and/or alcohol (for the previous 12 months before trial enrolment).
- •The participant has a history of occupational exposure to any radiation >50 millisievert/year (mSv/year).
- •The participant has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening and/or any radiopharmaceutical within a minimum of 5 radioactive half-lives prior to screening.
- •The participant presents with symptoms suggestive of corticobasal degeneration or Huntington's disease.
- •The participant has known allergies to the investigational medicinal product (IMP).
- •The participant presents with any clinically active, serious, life-threatening disease with a life expectancy of less than 12 months.
- •Any laboratory value(s) exceeding the limits of normality if deemed to be clinically relevant by the investigator.
- •The participant complains of claustrophobia.
- •The participant has a moderate to severe thyroid disease (thyroid stimulating hormone [TSH] exceeding the limits of normality by more than 10%), if deemed to be clinically relevant by the investigator.
- •For participants with ET:
- •The participant has at least 1 first-degree relative diagnosed with PD.
- •For Healthy Volunteers:
- •History of psychiatric illness.
- •For all participants:
- •It is the physician's best judgment not to include the participant in the trial.
研究组 & 干预措施
DaTSCAN™ ioflupane (123I) injection
Participants with Parkinsonian Syndrome (PS), Essential Tremor (ET), and Healthy Volunteers (HV) received a single dose of DaTSCAN™ ioflupane (123I) injection. Single photon emission computed tomography (SPECT) imaging was performed between 3 to 6 hours post-injection and lasted approximately 20 minutes to 1 hour.
干预措施: DaTSCAN™ Ioflupane (123I) Injection (Drug)
结局指标
主要结局
Sensitivity Analysis of the Blinded Independent Read of DaTSCAN™ SPECT Images
时间窗: At Day 1
Sensitivity was defined as positive percentage agreement and calculated as the number of true positives (TP) / (number of TP + number of false negatives \[FN\]): TP/(TP + FN), and a 2-sided 95% binomial confidence interval constructed around it. Only the participants with a clinical diagnosis of PS were included in the sensitivity analysis. The sensitivity of the blinded independent read of DaTSCAN™ SPECT images in detecting or excluding striatal dopaminergic deficit (SDD), when the clinical diagnosis as established by the investigator was used as the standard of truth, were summarized with by reader. Each participant's SPECT image was read by 3 blinded readers.
Specificity Analysis of the Blinded Independent Read of DaTSCAN™ SPECT Images
时间窗: At Day 1
Specificity was defined as negative percentage agreement and calculated as the number of true negatives (TN) / (number of TN + number of false positives \[FP\]): TN/(TN + FP), and a 2-sided 95% binomial confidence interval constructed around it. For the specificity analysis, only participants with a clinical diagnosis of ET were included; the HVs were excluded from this analysis. The specificity of the blinded independent read of DaTSCAN™ SPECT images in detecting or excluding striatal dopaminergic deficit (SDD), when the clinical diagnosis as established by the investigator was used as the standard of truth, were summarized with by reader. Each participant's SPECT image was read by 3 blinded readers.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Serious TEAEs(From start of study drug administration up to Day 4)
- Normalized DaTSCAN™ Uptake Based on Region Of Interest (ROI) With Central Read (by Semi-quantitative Assessment by Use of DaTQUANT™) of DaTSCAN™ SPECT Images(At Day 1)