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

Nanogen Pharmaceutical Biotechnology Joint Stock Company1 site in 1 country24 target enrollmentMay 25, 2016

ConditionsBreast Cancer

InterventionsPegfilgrastim

DrugsPegfilgrastim

Overview

Phase: Phase 1
Intervention: Pegfilgrastim
Conditions: Breast Cancer
Sponsor: Nanogen Pharmaceutical Biotechnology Joint Stock Company
Enrollment: 24
Locations: 1
Primary Endpoint: Area under the curve from time 0 to the last time point (AUC0-t) for serum Pegfilgrastim (PEG-GCSF)
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

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

Registry

clinicaltrials.gov

Start Date

May 25, 2016

End Date

November 6, 2017

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Nanogen Pharmaceutical Biotechnology Joint Stock Company

Responsible Party

Sponsor

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
•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.

Arms & Interventions

Pegcyte (Nanogen pegfilgrastim)

pegcyte 6 mg in the first cycle

Intervention: Pegfilgrastim

Neulastim (Roche pegfilgrastim)

Neulastim 6 mg in the first cycle

Intervention: Pegfilgrastim

Outcomes

Primary Outcomes

Area under the curve from time 0 to the last time point (AUC0-t) for serum Pegfilgrastim (PEG-GCSF)

Time Frame: 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

(AUC0-t)

Secondary Outcomes

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)
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)
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)
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 (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)
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)
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.)
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)
Incidence of adverse events(cycle 1 from day 2 to day 14)
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 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)