Ignite Creation Date:
2024-05-06 @ 1:56 AM
Last Modification Date:
2024-10-26 @ 11:11 AM
Study NCT ID:
NCT01933971
Status:
COMPLETED
Last Update Posted:
2013-09-09
First Post:
2013-08-29
Brief Title:
Evaluation of Dose-response Pharmacodynamic and Pharmacokinetic Bioequivalence of Filgrastim in Healthy Male Volunteers After Single and Multiple-dose Subcutaneous Administration of the Test Injectable Formulation BK0023 vs Neupogen
Sponsor:
Bio-ker Srl
Organization:
Bio-ker Srl
Study Overview
Official Title:
Evaluation of Dose-response Pharmacodynamic and Pharmacokinetic Bioequivalence of Filgrastim in Healthy Male Volunteers After Single and Multiple-dose Subcutaneous Administration of the BK0023 Injectable Formulation vs Neupogen
Status:
COMPLETED
Status Verified Date:
2013-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study rationale Bio-ker has developed the new formulation of filgrastim BK0023 with the same active content as Neupogen BK0023 is expected to have the same tolerability profile and clinical effects as Neupogen in controlling myelo-toxicity induced by chemotherapy given for the treatment of solid and haematological tumours It is worth noting that the production and manufacturing procedures allow to have a reduction of drug cost thus it is likely to have pharmacoeconomic advantages
The study is aimed at investigating the pharmacodynamic equivalence and the pharmacokinetic bioequivalence of the new BK0023 injectable formulation of filgrastim 03 mgmL by Bio-Ker Srl vs the comparator Neupogen 03 mgmL Dompé Biotec SpA Italy Healthy male subjects will receive test and reference at the doses of 25 and 5 µgkgday for 7 consecutive days and at the dose of 10 µgkgday for 5 consecutive days according to a randomised cross-over design Pharmacodynamics pharmacokinetics and safety of BK0023 injectable formulation 03 mgmL and of Neupogen 03 mgmL administered in 2 consecutive periods with a wash-out of at least 28 days elapsing between the last injection of period I and the first of period II are compared
Study design Single and multiple escalating dose double-blind randomised two-way cross-over pharmacodynamic and pharmacokinetic bioequivalence study
The study is aimed at investigating the pharmacodynamic equivalence and the pharmacokinetic bioequivalence of the new BK0023 injectable formulation of filgrastim 03 mgmL by Bio-Ker Srl vs the comparator Neupogen 03 mgmL Dompé Biotec SpA Italy Healthy male subjects will receive test and reference at the doses of 25 and 5 µgkgday for 7 consecutive days and at the dose of 10 µgkgday for 5 consecutive days according to a randomised cross-over design Pharmacodynamics pharmacokinetics and safety of BK0023 injectable formulation 03 mgmL and of Neupogen 03 mgmL administered in 2 consecutive periods with a wash-out of at least 28 days elapsing between the last injection of period I and the first of period II are compared
Study design Single and multiple escalating dose double-blind randomised two-way cross-over pharmacodynamic and pharmacokinetic bioequivalence study
Detailed Description:
In a first part of the study 16 healthy male subjects will be included in each dose group and will receive test and reference product according to the cross-over design After the end of the second period of each dose group completion of both cross-over periods for each dose group the pharmacodynamic and pharmacokinetic primary parameters will be calculated The blinding will be temporarily broken by one statistician for the ad interim analysis of primary parameters that will be performed after conclusion of the treatment of 16 subjects for each dose group results are not disclosed with the aim to re-calculate the sample size and to conclude the study with the necessary and sufficient number of subjects for each dose regimen
The study design was chosen according to the internationally recognised guideline for pharmacokinetics studies and in accordance with the EMEA guidance on similar medicinal products containing recombinant granulocyte-colony stimulating factor G-CSF which is annexed to the guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance non-clinical and clinical issues A clinical development plan including the study outline was also submitted to EMEA which examined the documentation and gave advice about the present study design
A multiple-dose design was chosen instead of a single-dose design since G-CSF pharmacokinetics is non linear due to 2 reasons non-proportional increase with dose and time dependent non-linearity However pharmacodynamic equivalence and pharmacokinetic bioequivalence will be both tested after the 1st and the last dose of the multiple dose treatment
Since the effects of r-h-met-G-CSF can be directly measured as pharmacodynamic responses ie the increase in the absolute neutrophil count ANC and the development of peripheral blood cells CD34 cells both parameters will be evaluated for the equivalence testing
Dose levels of 25 and 5 μgkgday were chosen for the pharmacodynamic equivalence since literature data show a clear dose-response relationship in terms of the pharmacodynamic parameters over this range The 10 μgkgday dose was chosen to make the investigated range relevant with respect to the clinical indications and the usual praxis for Neupogen Moreover the subcutaneous administration was chosen since this administration route is the most commonly used in the clinical setting
The study design was chosen according to the internationally recognised guideline for pharmacokinetics studies and in accordance with the EMEA guidance on similar medicinal products containing recombinant granulocyte-colony stimulating factor G-CSF which is annexed to the guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance non-clinical and clinical issues A clinical development plan including the study outline was also submitted to EMEA which examined the documentation and gave advice about the present study design
A multiple-dose design was chosen instead of a single-dose design since G-CSF pharmacokinetics is non linear due to 2 reasons non-proportional increase with dose and time dependent non-linearity However pharmacodynamic equivalence and pharmacokinetic bioequivalence will be both tested after the 1st and the last dose of the multiple dose treatment
Since the effects of r-h-met-G-CSF can be directly measured as pharmacodynamic responses ie the increase in the absolute neutrophil count ANC and the development of peripheral blood cells CD34 cells both parameters will be evaluated for the equivalence testing
Dose levels of 25 and 5 μgkgday were chosen for the pharmacodynamic equivalence since literature data show a clear dose-response relationship in terms of the pharmacodynamic parameters over this range The 10 μgkgday dose was chosen to make the investigated range relevant with respect to the clinical indications and the usual praxis for Neupogen Moreover the subcutaneous administration was chosen since this administration route is the most commonly used in the clinical setting
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2007DR1116 | OTHER | Swissmedic | None |