A Study to Evaluate the Safety, Biodistribution, Internal Radiation Dosimetry, and Effective Dose of DaTSCAN™ Ioflupane (123I) Injection in Chinese Healthy Volunteers.

Study Overview
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Brief Summary
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This is a phase 1, single-centre, single-group, nonrandomized, noncomparative, open-label, single-dose study to evaluate the safety, biodistribution, internal radiation dosimetry, and effective dose of DaTSCAN™ ioflupane (123I) injection in Chinese Healthy Volunteers.

Official Title
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A Phase 1, Non-randomised, Noncomparative, Open-label Study to Assess the Safety, Biodistribution, and Internal Radiation Dosimetry of a Single Dose of DaTSCAN™ Ioflupane (123I) Injection in Chinese Healthy Volunteers

Conditions
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Healthy Subjects (HS)

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: Chinese male or female who has agreed to sign and date the written informed consent form Age 18-70 years Body mass index (BMI) of 18-30 kg/m^2 General good state of health as judged by a qualified physician after completing physical examination Fit, co-operative, and able to provide consent Exclusion Criteria: Sensitivity to DaTSCAN™ ioflupane (123I) injection or any of its ingredients A history of motor disturbances A history of pulmonary, cardiovascular, neurological, renal or hepatic, hormonal or coagulation disorders or hyperthyroidism A history of drug, alcohol, or solvent abuse The subject has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening Radionuclide injection within a minimum of 5 radioactive half-lives prior to screening Use of any medication (except paracetamol [acetaminophen] or oral contraceptive), including traditional Chinese medicine, within 2 weeks prior to the imaging visit Classification as a radiation worker Women of child-bearing potential not accepting a highly effective method of birth control (A woman is considered of child-bearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Postmenopausal is defined as 12 months with no menses without an alternative medical cause, in International Council on Harmonisation (ICH) M3 (R2); A highly effective method of birth control is defined as one which results in a low failure rate (i.e., less than 1 % per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomised partner, in ICH M3 (R2). Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 will receive a single intravenous (IV) injection of DaTSCAN™ ioflupane (123I) injection into an arm vein, followed by planar whole-body imaging at prespecified time points over a period of 48 hours after administration. Brain SPECT imaging will be acquired at 3 and 6 hours after administration. | Drug: DaTSCAN™ Ioflupane (123I) Injection<br>* Each participant will receive a single administration of DaTSCAN™ ioflupane (123I) injection by bolus IV injection with a nominal iodine (123I) activity of 111 MBq ±10%, in a maximum volume of 5 mL.<br>* Other names: Ioflupane (123I);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in participants or clinical investigation participant which did not necessarily have to have been related to the investigational medical product (IMP). AEs were recorded from time of informed consent through the follow-up visit at 2 weeks (±2 days) after IMP administration. | Baseline up to 2 weeks after IMP administration (i.e., up to 16 days) | 
| Change From Baseline in Tolerability Questionnaire Score at Approximately 15 Minutes, 1, 4, 24, 48 Hours After DaTSCAN™ Ioflupane (123I) Injection as Measured by VAS (Visual Analogue Scale) | Tolerability questionnaire evaluated participants mood, pain at injection site, itchiness of injection site, loss of function at injection site and quality of sleep using 100 millimeter (mm) VAS. VAS is a continuous scale comprised of a horizontal line, usually 100 mm in length, where 0 stands for bad, and 100 mm stands for good. Higher score indicated better health outcomes. | 1 hour before injection (baseline), and at approximately 15 minutes, 1, 4, 24, 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings Pre-specified Timepoints | Physical examination included recording an assessment for the presence of abnormalities of the following: general appearance, skin, lungs, cardiovascular system, back and spine, abdomen, extremities, lymph nodes, and neurological exam. Clinical significance was determined by investigator. | Baseline, 4 hours after injection and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Hematology Parameters at Pre-specified Timepoints | Change from baseline in activated partial thromboplastin time, prothrombin time, thrombin time were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Hematology Parameter-C Reactive Protein at Pre-specified Timepoints | Change from baseline in C reactive protein were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Hematology Parameter-Hematocrit at Pre-specified Timepoints | Change from baseline in hematocrit were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Hematology Parameter-Erythrocytes at Pre-specified Timepoints | Change from baseline in erythrocytes were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Hematology Parameters- Leukocytes, Platelets at Pre-specified Timepoints | Change from baseline in leukocytes, platelets timepoints were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Hematology Parameters- Fibrinogen, Hemoglobin at Pre-specified Timepoints | Change from baseline in fibrinogen, hemoglobin were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Serum Chemistry Parameters- Albumin, Protein at Pre-specified Timepoints | Change from baseline in albumin, protein were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Serum Chemistry Parameters- Thyroxine, Free and Triiodothyronine, Free at Pre-specified Timepoints | Change from baseline in thyroxine, free and triiodothyronine, free were reported. | Baseline, and at 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Change From Baseline in Serum Chemistry Parameters at Pre-specified Timepoints | Change from baseline in alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatine kinase, gamma glutamyl transferase, lactate dehydrogenase were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Serum Chemistry Parameters- Thyroxine and Triiodothyronine at Pre-specified Timepoints | Change from baseline in thyroxine and triiodothyronine were reported. | Baseline, and at 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Change From Baseline in Serum Chemistry Parameters- Bilirubin, Creatinine, Direct Bilirubin, and Urate at Pre-specified Timepoints | Change from baseline in bilirubin, creatinine, direct bilirubin, and urate were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Serum Chemistry Parameters- Bicarbonate, Calcium, Chloride, Glucose, Phosphate, Potassium, Sodium, Urea Nitrogen at Pre-specified Timepoints | Change from baseline in bicarbonate, calcium, chloride, glucose, phosphate, potassium, sodium, urea nitrogen were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Serum Chemistry Parameters- Thyrotropin at Pre-specified Timepoints | Change from baseline in thyrotropin were reported. | Baseline, and at 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Change From Baseline in Serum Chemistry Parameters- Amylase at Pre-specified Timepoints | Change from baseline in amylase were reported. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Number of Participants With Clinically Significant Abnormal Urinalysis Parameters - pH and Specific Gravity at Pre-specified Timepoints | Number of participants with clinically significant abnormal pH and specific gravity were reported. Clinical significance was determined by investigator. | Baseline, and at approximately 3 hours, 48 hours, and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Number of Participants Who Reported Abnormal Injection Site Monitoring Findings at Pre-specified Timepoints | Any radiopharmaceutical extravasation, bleeding, hematoma, redness, infection, or other findings were considered as abnormal findings. | Baseline, up to 4 hours after DaTSCAN™ ioflupane (123I) injection | 
| Change From Baseline in Vital Sign-Systolic Blood Pressure at Pre-specified Timepoints | Change from baseline in systolic blood pressure were reported. | Baseline, 10, 20, 30 minutes and 1, 2, 4, 24, 48 hours and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Vital Sign-Diastolic Blood Pressure at Pre-specified Timepoints | Change from baseline in diastolic blood pressure were reported. | Baseline, 10, 20, 30 minutes and 1, 2, 4, 24, 48 hours and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Vital Sign-Heart Rate at Pre-specified Timepoints | Change from baseline in heart rate were reported. | Baseline, 10, 20, 30 minutes and 1, 2, 4, 24, 48 hours and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Vital Sign-Temperature at Pre-specified Timepoints | Change from baseline in temperature were reported. | Baseline, 10, 20, 30 minutes and 1, 2, 4, 24, 48 hours and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Vital Sign-Respiratory Rate at Pre-specified Timepoints | Change from baseline in respiratory rate were reported. | Baseline, 10, 20, 30 minutes and 1, 2, 4, 24, 48 hours and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Oxygen Saturation at Pre-specified Timepoints | Change from baseline in oxygen saturation were reported. | Baseline, 10, 20, 30 minutes and 1, 2, 4, 24, 48 hours and 2 weeks after DaTSCAN™ ioflupane (123I) injection (i.e., up to 16 days) | 
| Change From Baseline in Electrocardiogram (ECG) Findings at Pre-specified Timepoints | Change from baseline in PR interval, QRS interval, QT interval, QTC interval, RR interval, QTCF interval, QTCB interval were reported. | Baseline, 2 and 5 hours after DaTSCAN™ ioflupane (123I) injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution Measured by Decay Corrected Percentage Injected Activity (%IA) in Blood (Plasma and Whole Blood) | The decay-corrected %IA was measured by planar scintigraphy. The biodistribution as measured by the decay-corrected %IA in the plasma and whole blood at specified timepoints were reported. | Pre-dose, 5, 15, 30 minutes and 1, 2, 3, 4, 5, 24, and 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Biodistribution Measured by Decay Corrected Percentage Injected Activity (%IA) in Whole Body Image | The decay-corrected %IA was measured by planar scintigraphy. The biodistribution as measured by the decay-corrected %IA in the whole-body image which included background, heart, intestines, liver, lungs, salivary glands, stomach, striatum, thyroid, whole body, whole brain) at specified timepoints were reported. | 10 minutes and 1, 2, 4, 5, 24, and 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Biodistribution by Source Regions Measured by Decay Corrected Normalized Cumulative Activity | Biodistribution measured by decay corrected normalized cumulative activity in bladder content, brain, gallbladder, liver, lower large intestine, lungs, remainder, small intestine, upper large intestine was reported. | Up to 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Biodistribution as Measured by Decay-corrected Cumulative 123I Activity Concentration in Excreted Urine | Excretion of 123I following the IV administration of ioflupane (123I) Injection was determined by measuring the 123I activity within the intestinal contents and the sum of the 123I activities in the voided urine up to 48 hours post-injection. | 10 minutes and 1, 2, 3, 4, 5, 5 to 24, and 24 to 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Normalized Organ Absorbed Doses as Measured by Radiation Dosimetry | Sex-averaged normalized organ absorbed doses calculated according to Medical Internal Radiation Dose (MIRD) method. | Up to 48 hours after DaTSCAN™ ioflupane (123I) injection | 
| Effective Dose (ED) of Ioflupane (123I) Injection After IV Administration | The ED per unit of administered activity was evaluated from the ensemble of absorbed dose data. | Up to 48 hours after DaTSCAN™ ioflupane (123I) injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single photon emission computed tomography (SPECT), Healthy Volunteer (HV)