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This is a single-center, open-label, single-dose phase I study to investigate the absorption, metabolism and excretion of [14C] D-0316 in healthy Chinese male subjects. The study will be conducted into two steps:Firstly, 2 subjects are enrolled in to participate in the pilot study to grope for the completion date of plasma, urine and feces sampling on the 3rd day post-dose and onwards. Then, the collection time of blood and excreta samples (urine and feces) from the subsequent 2-4 subjects will be adjusted according to the pilot study
Subjects who had signed informed consent and meet inclusion criteria and no exclusion criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an overnight fast of at least 10 h, subjects will receive a single oral dose of 75 mg (50 μCi) of [14C]D-0316 as an oral suspension. Then, after two days of the dosing, subjects will be transferred back to Phase I Clinical Unit ward and confined to this unit until blood or excreta sampling and safety monitoring at the designated time points or intervals are complete
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [14C]D-0316 | Experimental | To investigate the absorption properties, as well as to evaluate the mass balance and elucidate the pathways of biotransformation after a single oral dose (75mg, 50µCi) of [14C]D-0316 to healthy Chinese male subjects |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [14C]D-0316 suspension | Drug | Before administration, the drug preparation was placed at room temperature, and 40ml drinking water was added into each bottle to prepare suspension for the subjects to take. 40ml pure water was injected again. After washing the container, the subjects took orally. Repeat the previous step, and then used 160ml purified water. After the administration container was moistened for several times, the subjects took all the moistening lotion. Pay attention not to splash the liquid during mixing outside the bottle |
| Measure | Description | Time Frame |
|---|---|---|
| Radioactivity concentration of each plasma sample | Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each plasma(DPM/ml) sample | Day 1-Day85 |
| Radioactivity concentration of each urine samples | Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each urine(DPM/ml) sample | Day-1-Day85 |
| Radioactivity concentration of each feces sample | Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each feces(DPM/ml) sample | Day-1-Day85 |
| Total recovery of radioactivity in urine and feces | Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample | Day-1-Day85 |
| Identification of metabolites in plasma, urine and fecal samples | LC-MS/MS was used to identify the main metabolites in plasma, urine and feces, and finally to provide the main biotransformation pathway of CM082 in human body | Day-1-Day85 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic parameters of unlabeled D-0316 and metabolite D-0865 | To determine the plasma concentrations of D-0316 with validated LC-MS/MS method for obtaining its pharmacokinetics parameters | Day-1-Day85 |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Feng Shao, Ph D | Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine | Principal Investigator |
| Wei Liu, M.A | Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine | Nanjing | Jiangsu | 210029 | China |
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According to CTCAE v4.03, the number and frequency of adverse events after a single dose of test drug were assessed |
| Day-14-Day85 |