Altropane Dose for Imaging Patients With Suspected Parkinson's Disease

Study Overview
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Brief Summary
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Previous studies showed that a dose of 8 millicuries of Altropane was appropriate for imaging patients with suspected Parkinson's disease. This study will determine if a lower dose (5 millicuries) would suffice.

Official Title
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An Open-label Multicenter Phase 2 Dose-evaluation Study of Altropane (123I) Injection for Striatal Dopamine Transporter Visualization Using SPECT Brain Imaging

Conditions
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Parkinson Disease, Movement Disorders

Intervention / Treatment
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* Drug: Altropane (123I) Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Part 1: a) the patient has a DaTscan image, obtained within 1 year (preferably within 6 months) before screening, that shows normal striatal uptake and b) the patient has a clinical diagnosis (made by a board-certified neurologist who is qualified by training and experience in the diagnosis of movement disorders) that is consistent with the DaTscan image. For Part 2 (if applicable): a) the patient has a DaTscan image, obtained within 1 year (preferably within 6 months) before screening, that shows abnormal (unilateral or bilateral reduced) striatal uptake and b) the patient also has a confirmed clinical diagnosis of a dPS (such as Parkinson's disease, multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, etc.) made by a board-certified neurologist who is qualified by training and experience in the diagnosis of movement disorders, and c) the diagnosis is consistent with the DaTscan image. The patient is male or female, ≥18 years of age, of any race and ethnicity. The patient is able and willing to comply with study procedures and signed and dated informed consent is obtained. If the patient is a woman of childbearing potential*, she must use a highly effective method of contraception** from Screening until 30 days after the last administration of Altropane, and the results of a serum or urine human chorionic gonadotropin (hCG) pregnancy test, performed at Screening and on the day of Altropane administration (with the result known before Altropane administration), must be negative. * A woman of childbearing potential is neither post-menopausal nor surgically sterile. Post-menopausal means having had no menses for at least 12 months without an alternative medical cause. Surgically sterile means having had a documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or any combination of these. ** A highly effective method of contraception is one that has a failure rate of less than 1% per year when used consistently and correctly; such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal ligation/occlusion; vasectomized partner (with medical confirmation of success); and abstinence from heterosexual intercourse involving a woman of childbearing potential. If the patient is a male*** with a sexual partner who is a woman of childbearing potential*, he and his partner must use adequate contraception** from Screening until 30 days after the last administration of Altropane. (***A male is considered fertile after puberty unless permanently sterile by bilateral orchidectomy, or vasectomized with confirmation of success.) Exclusion Criteria: The patient was previously included in this study. Fewer than 7 disintegration half-lives have elapsed between the patient's last procedure (therapeutic or diagnostic) involving a radioisotope and Visit 2 (altropane SPECT imaging). Including participation in this study, the patient's total exposure to radiation during medical procedures/tests in the past year would exceed 50 mSv. The patient has participated in an investigational drug or device clinical trial within 30 days before the date of informed consent. The patient has any clinically significant or unstable physical or psychological illness, structural brain abnormality, abnormal laboratory results, or abnormal ECG (based on medical history or physical examination at Screening), as determined by the Principal Investigator, that would interfere with study participation. The patient has any history of drug or alcohol abuse in the 2 years prior to the date of informed consent. The patient has a positive urine screen for drugs of abuse at Screening. The patient is a pregnant or breast-feeding female, or is a female of child-bearing potential that is not using appropriate birth control. The patient is unable to lie supine for 1 hour. The patient has any thyroid disease other than adequately treated hypothyroidism. The patient has known or suspected allergy/hypersensitivity to any ingredient in Altropane or to the thyroid blocking medication to be used before imaging. The patient is currently taking any of the medications/treatments listed in the protocol as disallowed and cannot or will not discontinue use at least 12 hours prior to SPECT exam. The patient was referred to DaTscan imaging for evaluation of possible cognitive impairment including dementia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Altropane (123I) Injection<br> | Drug: Altropane (123I) Injection<br>* Each subject will receive a single IV administration of 5 mCi (185 MBq) Altropane.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Striatal uptake | Assessment of the Altropane SPECT images by 5 independent expert blinded readers to determine striatal uptake, reported as a forced choice of either normal (caudate and putamen fully visible on left and right, or with small insignificant defects) or abnormal (unilateral or bilateral reduced). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reader confidence | Reader confidence in striatal visualization, rating it as high, medium, or low | 30 days | 
| Reader Assessment of Image Quality | Each subject's image quality will be rated as excellent, good, fair, poor, or unevaluable. | 30 days | 
| Inter-reader agreement | Number and percentage of images for which 5, 4, and 3 readers, respectively, are in agreement on the subject classification for Part 1, and, if applicable, Part 2. | 30 days | 
| Altropane-related Serious Adverse Events |  | From administration of Altropane until 24 hours post dose | 
| Treatment-Emergent Adverse Events |  | From administration of Altropane until 24 hours post dose | 
| Adverse Events |  | From administration of Altropane until 24 hours post dose | 
| Number of participants with abnormal serum biochemistry laboratory test results. | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal hematology laboratory test results. | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal systolic and diastolic blood pressure (in millimeters of mercury [mmHg]). | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal body temperature (degrees Celsius). | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal heart rate (beats per minute [bpm]). | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal respiratory rate (breaths per minute) | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal electrocardiogram (ECG) examinations (PR interval, QTc, QRS and RR interval). | Baseline is the last observation prior to administration of Altropane. The occurrence of post-injection values outside of normal limits and changes from baseline will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 
| Number of participants with abnormal physical examination (general appearance, lungs and heart) findings. | Baseline is the last observation prior to administration of Altropane. The occurrence of post-administration physical exam status values outside the normal limits will be summarized. | Baseline (pre-Altropane) and within 60 minutes after imaging. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SPECT, Altropane, Parkinson's disease, Parkinsonian syndromes, movement disorders, striatum, dopamine transporter