pharmacokinetic/pharmacodynamic parameters of nng-depo (stimus) with aranesp® (amgen) in treatment of anemia in ckd patients on dialysis

Conditions: Chronic Kidney Disease

Summary: this is a double-blind, randomized, active-control study with 2-study arms-darbepoetin alfa biosimilar and aranesp, noninferiority trial design in dialysis patients. dialysis patients will be randomized into 1:1 ratio to receive either darbepoetin alfa or aranesp 0.75 µg/kg by subcutaneous injection every other week for 24 weeks. pharmacokinetic/pharmacodynamic parameters for evaluation are assessed as per study endpoints at defined time points on all patients. during the treatment, dose adjustments will be made as necessary to achieve a hemoglobin response, defined as maintaining hb in target range 10 - 12 g/dl.

phase of trial: i sample size: 43 for pharmacokinetic/pharmacodynamic parameters target population: patients with chronic kidney disease undergoing dialysis study groups: 1. darbepoetin alfa (nanogen) sc 0.75 µg/kg q2w, for 24 weeks. 2. 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).

Eligibility criteria:
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.

Keywords: darbepoetin alfa nanogen ckd dialysis treatment of anemia