Pharmacokinetic/Pharmacodynamic Parameters of NNG-DEPO (Stimus) With Aranesp® (Amgen) in Treatment of Anemia in CKD Patients on Dialysis

PHASE OF TRIAL: I SAMPLE SIZE: 43 for pharmacokinetic/pharmacodynamic parameters TARGET POPULATION: Patients with chronic kidney disease undergoing dialysis

STUDY GROUPS:

• Darbepoetin alfa (Nanogen) SC 0.75 µg/kg Q2W, for 24 weeks.
• Aranesp® (Amgen) SC 0.75 µg/kg Q2W, for 24 weeks.

PK ASSESSMENT: Blood samples for PK assessments will be collected at:

• IV: time zero (predose) before injection of study drug and then after 0.25, 0.5, 4, 12, 24, 48, 96, 144, 240 and 336 hours post-dose.
• SC: time zero (predose) before injection of study drug and then after 4, 12, 24, 48, 96, 144, 240 and 336 hours post-dose.

PD ASSESSMENT: Blood samples for PD assessments will be collected at time zero (predose) before injection of study drug and then after 24, 48, 96, 144, 240 and 336 hours post-dose.

SAFETY AND TOLERABILITY ASSESSMENT:

Safety and tolerability assessments will be performed at each visit. Following variables will be considered to define the safety and tolerability of investigational drugs:

• Clinical adverse events (AEs): frequency of AEs, overall and by intensity.
• Severe clinical adverse events (SAEs): frequency of AEs, overall and by intensity.
• Symptoms directed physical examination including body weight, and vital signs during treatment period: mean change from baseline and the frequency of clinically relevant changes from baseline.
• Laboratory tests: frequency of clinically relevant changes from baseline.
• The frequency of any concomitant medication administered to treat any adverse events.
• Presence of anti-bodies to darbepoetin alfa (immunogenicity).

Inclusion criteria

• The patients signed the informe consent form and adhere to study visit schedule.
• Male or female patients aged from 18 to 65 years.
• Patients on hemodialysis or peritoneal dialysis for at least 3 months and have Hb baseline <10 g/dL during the screening period.
• Have transferrin saturation ≥ 20%, serum ferritin ≥ 200 ng/mL, vitamin B12 and folate within the normal range.
• Have expected survival of at least 6 months from time of enrollment (by investigator's assessment).
• Women childbearing age must agree to use medically acceptable methods of contraception during the study and for 6 months after the last study treatment.
• The patient does not have any serious medical conditions that may affect to study treatment compliance.

Exclusion criteria

• Uncontrolled hypertension over 2 weeks prior to and within the screening period (BP ≥ 160/90 mmHg).
• Patients treated with Darbepoetin alfa or r-HuEPO within 4 weeks prior to enrollment.
• Patients with Uncontrolled diabetes mellitus with HbA1C ≥ 10%.
• Congestive Heart Failure of grade 3 or 4 as New York Heart Association classification.
• History of unstable angina or myocardial infarction within 6 months.
• History of Grand mal seizures in last 2 years.
• Present with severe hyperparathyroidism (iPTH >1500 pg/mL for Dialysis).
• History of major surgery within 12 weeks prior to screening.
• Systemic hematologic disorders including sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma and hemolytic anemia.
• Systemic infections, active inflammatory diseases and malignancies.
• Active liver disease or hepatic with liver enzymes AST and ALT raised > 2-times of laboratory normal values, child B or child C cirrhosis.
• Are being treated with androgen therapy within the 8 weeks prior to the screening period.
• Pregnant or suspected pregnant women, breast-feeding women.
• Patients scheduled for any transplant procedure within 6 months of screening or with a previous history of kidney transplantation.
• Patients who are hypersensitive to any of substances of investigational product.
• Patients using drugs that can affect the concentration of Hb in the blood (except blood-forming drugs such as iron, folic acid).
• Patients with seropositivity to HIV, HBV or anti-HCV.
• Patients having acute tuberculosis or any acute bacterial infection within 1 month prior to the screening.
• Patient has occult blood in stool or any other known source of internal bleeding and confirmed gastrointestinal bleeding by endoscopy.
• Patients with blood transfusion due to acute bleeding within 12 weeks prior to screening period.
• Patients with a history of immunosuppressive therapy within 1 month.
• The patient is suffering from advanced cancer.
• Patients having participated in any other clinical trial within 1 month prior to the screening period.
• The patient had any medical condition that the investigator assessed as affecting the study.