A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Parkinsonian Syndrome, Parkinson Disease(PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), Essential Tremor

Intervention / Treatment
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* Drug: DaTSCAN™ Ioflupane (123I) Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) . Exclusion Criteria: 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 <24. 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DaTSCAN™ ioflupane (123I) injection<br>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. | Drug: DaTSCAN™ Ioflupane (123I) Injection<br>* All participants (Participants with PS, ET, and HV) received a single dose of DaTSCAN™ ioflupane (123I) injection within the range of 111 to 185 megabecquerel (MBq) (3 to 5 millicurie [mCi]) per participant at a maximum volume of 5 milliliter [mL]) intravenously on Day 1.<br>* Other names: Ioflupane (123I);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity Analysis of the Blinded Independent Read of DaTSCAN™ SPECT Images | 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. | At Day 1 | 
| Specificity Analysis of the Blinded Independent Read of DaTSCAN™ SPECT Images | 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. | At Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalized DaTSCAN™ Uptake Based on Region Of Interest (ROI) With Central Read (by Semi-quantitative Assessment by Use of DaTQUANT™) of DaTSCAN™ SPECT Images | A semi-quantitative analysis of the striatal uptake ratios in specific regions of interest (ROIs, i.e., left and right striatum, caudate, and putamen) of DaTSCAN™ SPECT images was performed with DaTQUANT™. | At Day 1 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Serious TEAEs | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. A Serious Adverse Event(SAE) was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. A TEAE was any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. Number of participants with TEAEs and serious TEAEs were reported. | From start of study drug administration up to Day 4 |