PK & PD Study of Pegylated rhEPO, and Evaluated Its Safety and Tolerability in Male Healthy Individual

Study Overview
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Brief Summary
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The object of this randomized, parallel, positive controlled study is to explore the pharmacokinetics and pharmacodynamics profile of the test drug after single-dose subcutaneous administration, compared to the comparator drug (EPIAO®) after multiple-dose subcutaneous administration, by assessing plasma concentration of the drug and the reticulocyte count, hemoglobin concentration and hematocrit following subcutaneous administration, evaluate the security and tolerability of the test drug in healthy subjects, and provide sufficient information for dose selection in the future phase II and III study.

Official Title
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A Randomized, Positive-controlled, Single-dose, Dose-escalation Phase I Trial to Evaluate Safety & Tolerability, and Explore the Pharmacokinetics and Pharmacodynamics Profile of Pegylated rhEPO in Male Healthy Individual

Conditions
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Healthy

Intervention / Treatment
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* Drug: Pegylated rhEPO
* Drug: EPIAO®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agree to all the purposes of the study by signing and dating the informed consent. Male, aged between 18 and 40 years, age disparity of each group should less than 10 years. Body weight ≥ 50kg, and body mass index (BMI) between 18 kg/m2 and 26kg/m2 at screening. Hemoglobin between 131g/L and 162g/L, hematocrit between 41% and 49%, and reticulocyte between 0.5% and 2%. Transferrin saturation and serum ferritin are in the normal range. Physical condition: vital signs, physical examination and laboratory tests ( including routine blood, biochemical tests, coagulation indicators, serum folic acid, vitamin B12, urine test, HBsAg, anti-HCV, anti-HIV, Immunoglobulin (IgA, IgM, IgG), thyroid function (T3, T4, TSH), autoantibodies), chest-X-ray, 12-lead ECG should all in normal range, or without significant clinically abnormal. Exclusion Criteria: Presence of organic disease in heart, liver, kidney, brain; or presence of cardiovascular, pulmonary, gastrointestinal, urinary, neurological, endocrine, immunity, genitourinary or other systems disease. Subjects with familial genetic disease, mental illness, or physical disability. History of drug allergy. Orthostatic hypotension, systolic blood pressure <90mmHg. Habitual medication, including Chinese herbal medicine. Poor inclusion conditions (e.g. infirm). Smoker (smoke everyday or more than 7 cigarettes per week)，alcoholics (more than 40g/day, equivalent to 100ml/day of 50 degree of white spirit). Participate in any other drug trials as the subjects within the previous 3 months. As blood donated within the previous 3 months, or experienced massive blood loss due to trauma or surgery. Other conditions which in the opinion of the investigator precluding enrollment into the study (e.g. poor compliance).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegylated rhEPO<br>Subcutaneous single-dose administration of 0.5mcg/kg, 1.0mcg/kg, 1.6 mcg/kg, 2.4 mcg/kg, 3.2 mcg/kg，3.2mcg/kg, 4.2mcg/kg, 5.5 mcg/kg, 7.2 mcg/kg, 9.3 mcg/kg (in dose-escalation, if the previous dose is confirmed to be safe.started with the second 3.2mcg/kg dose,Every subject takes Niferex 150mg every day, from day 1 to day 20. ) of the test drug (Pegylated rhEPO) | Drug: Pegylated rhEPO<br> <br> |
| Active Comparator: EPIAO®<br>Subcutaneous six-dose administration of 50IU/kg or 150IU/kg, as randomization, of the comparator drug(EPIAO®) at day 1, 3, 5, 8, 10, 12. | Drug: EPIAO®<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of rhEPO | Time frame of day 12 for comparator drug: 0 hour before drug administration and 1, 3, 6, 9, 14, 16 hour after last dose administration. For comparator drug, blood collection of 0, 48, 96, 168, 216, and 264 hour should before drug administration. | 0 hour before drug administration and 1, 3, 6, 9, 12, 14, 16, 24, 36, ,48, 72, 96, 120, 144, 168, 192, 216,240, 264, 288, 300, 312, 360, 408, 480, 648, 984,1320 hour after drug administration | 
| Plasma reticulocyte count | For comparator drug, blood collection of 48, 96, 168, 216, and 264 hour should before drug administration | 0 hour before and 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 360, 408, 480, 648,984,1320 hour after first drug administration. | 
| Plasma hemoglobin concentration | For comparator drug, blood collection of 48, 96, 168,216, and 264 hour should before drug administration | 0 hour before and 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 360, 408, 480, 648,984,1320 hour after first drug administration. | 
| Plasma hematocrit | For comparator drug, blood collection of 48, 96, 168,216, and 264 hour should before drug administration | 0 hour before and 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 360, 408, 480, 648,984,1320 hour after first drug administration. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK & PD study, rhEPO, Pegylated rhEPO, male healthy subject