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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pegylated rhEPO; Drug: EPIAO®

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 302 Military Hospital of China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegylated rhEPO; 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
Active Comparator: EPIAO®; 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®

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Xiamen Amoytop Biotech Co., Ltd.
• Investigators: Principal Investigator: Wei Zhenman, Ph.D, Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: February 24, 2013
• First Submitted That Met QC Criteria: February 25, 2013
• First Posted (Estimate): February 27, 2013

Study Record Updates

• Last Update Posted (Estimate): August 31, 2015
• Last Update Submitted That Met QC Criteria: August 27, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: PK & PD study; rhEPO; Pegylated rhEPO; male healthy subject
• Other Study ID Numbers: TB1209EPO