Nanogen Pegfilgrastim (Pegcyte) PK/PD Clinical Study in Breast Cancer Patients

Study Overview
=================
Brief Summary
-----------------
Breast cancer patients scheduled to receive myelosuppressive chemotherapy (AC regimen) will be enrolled in this study. Eligible patients receive single SC injection of pegcyte or neulastim 24 hours after administration of chemotherapy (Doxorubicin and Cyclophosphamide) in the first cycle (14 days each cycle). Blood samples are collected to determine the serum concentration of investigational drugs at specific time points in the first cycle. Absolute neutrophil count, CD34+ count, Cmax (maximum serum concentration), AUC0-t (area under the curve of the plasma concentration time) and Tmax (time required to reach Cmax) will be calculated from the serum concentration profile

Official Title
-----------------
A Randomized, Double-blind, Parallel Study Comparing Pharmacokinetic (PK) and Pharmacodynamic (PD) Parameters of Pegcyte (Nanogen) and Reference Product Neulastim (Roche) for Chemotherapy-induced Neutropenia in Breast-cancer Patients

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Pegfilgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female patients aged between 18 - 65 years. Patients with histological confirmed primary invasive breast cancer; stage I, II or III. Patients had no prior chemotherapy treatments. Patients scheduled to undergo myelosuppressive Doxorubicin and Cyclophosphamide chemotherapy for 04 cycles, and Paclitaxel chemotherapy for the next 04 cycles; patients were available for 14 days of each cycle for the first 03 chemotherapy cycles. Patients with baseline ANC ≥ 1.5 x 109/L, PLT ≥ 100 x 109/L, HgB ≥ 9 g/dL, WBC ≥ 3,000/mL and albumin ≥ 3.0 g/dL. Performance status as per ECOG (Eastern Cooperative Oncology Group) score 0, 1 or 2. Willing to give written and signed informed consent Exclusion Criteria: Patients with prior exposure of G-CSF or GM-CSF or its pegylated products in clinical development less than 6 months prior to randomization. Myelotoxic concomitant treatment such as chloramphenicol, methotrexate, immunomodulating agents, interferons during 10 days before randomization. Received systemic antibiotic treatment within 72 hours of chemotherapy. Chronic use of corticosteroids, prior bone marrow or stem cell transplant. Patients who had an immediate/ concurrent exposure to radiotherapy or surgery (within 4 weeks). Severe medical disease: cardiovascular, hepatic, renal, pulmonary… Known cases of hematological disease (sickle cell anemia, AML…) History of HIV positive, active hepatitis. Pregnant and lactating women or patients planning to become pregnant. Known allergic reactions to study medications. Positive to anti-pegfilgrastim antibody test.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegcyte (Nanogen pegfilgrastim)<br>pegcyte 6 mg in the first cycle | Drug: Pegfilgrastim<br>* PK,PD and safety assessment<br>|
| Active Comparator: Neulastim (Roche pegfilgrastim)<br>Neulastim 6 mg in the first cycle | Drug: Pegfilgrastim<br>* PK,PD and safety assessment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from time 0 to the last time point (AUC0-t) for serum Pegfilgrastim (PEG-GCSF) | (AUC0-t) | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent clearance (CL) for serum Pegfilgrastim |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Maximum concentration (Cmax) for serum Pegfilgrastim |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Half-life (T½) for serum Pegfilgrastim (PEG-GCSF) |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Area under the serum concentration-time curve (AUC0-inf) of Pegfilgrastim |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Time to maximum concentration (Tmax) for serum Pegfilgrastim |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Terminal elimination rate constant (λz) for serum Pegfilgrastim |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Maximum change in CD34+ count |  | day 2 (0h), day 5 (72h), day 7 (120h), and day 8 (144h) of the first cycle. | 
| Area under the curve above baseline of ANC [ANC_AUC(0-tlast)] |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Time of maximum change from baseline for ANC in days (ANC_Tmax) |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Maximum change from baseline in absolute neutrophil count from time 0 to the last time point ANC AUC0-t |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Maximum change from baseline in absolute neutrophil count (ANC); ANC_Cmax |  | day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle | 
| Incidence of adverse events | Including changes in vitals and laboratory investigations | cycle 1 from day 2 to day 14 |