Healthy Male SubjectsPhase 1NCT01933971
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®
A Phase 1 study testing Filgrastim test and Filgrastim reference in people with Healthy Male Subjects, run by Bio-ker S.r.l. at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Male Subjects
- What is being tested?
- Filgrastim test and Filgrastim reference
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2007to Apr 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- a body mass index (BMI) between 18 and 28 kg/m2,
- a body weight between 60 and 90 kg,
- good health based on medical history, physical examination, a 12-lead electrocardiogram (ECG) and routine haematology and blood chemistry tests,
- willingness to provide written informed consent
- values of leukocytes and thrombocytes had to be inside the normality range at the screening.
Who cannot join
- intake of any concomitant medication,
- a history of drug, caffeine (>5 cups coffee/tea/day) or tobacco (>/=10 cigarettes/day) abuse, or alcohol consumption in excess of two drinks per day, as defined by the U.S.D.A. dietary guidelines,
- ascertained or presumptive hypersensitivity to the active compound or history of anaphylaxis to drugs.
Trial locations and contacts
1 site in 1 country.
About this study
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®
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 0.3 mg/mL by Bio-Ker S.r.l. vs. the comparator (Neupogen® 0.3 mg/mL, Dompé Biotec S.p.A., Italy). Healthy male subjects will receive test and reference at the doses of 2.5 and 5 µg/kg/day for 7 consecutive days and at the dose of 10 µg/kg/day for 5 consecutive days according to a randomised cross-over design. Pharmacodynamics, pharmacokinetics and safety of BK0023 injectable formulation 0.3 mg/mL and of Neupogen® 0.3 mg/mL, 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.
Read the 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, i.e. 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 2.5 and 5 μg/kg/day 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 μg/kg/day 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.
- Conditions
- Healthy Male Subjects
- Being tested
- Filgrastim test, Filgrastim reference
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Filgrastim testDrug
Also called r-metHuG-CSF, BK0023
0.3 mg/mL injectable solution in 1 mL vials Manufacturer (Drug Substance): Eurogenetec S.A., B-4102 Seraing, Belgium Manufacturer (Drug Product): Areta International S.r.l., I-21040 Gerenzano, Italy Batch release: Areta International S.r.l., I-21040 Gerenzano, Italy Route of administration: subcutaneous
Filgrastim referenceDrug
Also called r-metHuG-CSF, Neupogen®
0.3 mg/mL injectable solution in 1 mL vials Licensed owner: Dompé farmaceutici S.p.A., Milan, Italy Manufacturer (Drug Product): Hoffmann - La Roche Ltd., Basel, Switzerland and Amgen Manufacturing Limited, Puertorico.
Batch release: Amgen Europe B.V., Breda, Netherlands Route of administration: subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Group 1: filgrastim 2.5 µg/kg/day for 7 consecutive days | Other | The test investigational product is BK0023. The reference product is Neupogen® 30, by Dompé Biotec S.p.A., Italy.
Both study treatments were administered according to a cross-over design in 2 subsequent periods separated by wash-out periods of at least 28 days.
The sites, where the injections are to be performed, are planned as follows:
1. st injection: upper part of the upper arm, posterior surface
2. nd injection: upper part of the thigh
3. rd injection: abdomen with the exception of the umbilical area
4. th injection: upper part of the contra-lateral upper arm, posterior surface
5. th injection: upper part of the contra-lateral thigh
6. th injection: abdomen with the exception of the umbilical area
7. th injection: upper part of the same upper arm, posterior surface as for the 1st injection. Receives: Drug: Filgrastim test; Drug: Filgrastim reference |
| Group 2: filgrastim 5 µg/kg/day for 7 consecutive days | Other | The test investigational product is BK0023. The reference product is Neupogen® 30, by Dompé Biotec S.p.A., Italy.
Both study treatments were administered according to a cross-over design in 2 subsequent periods separated by wash-out periods of at least 28 days.
The sites, where the injections are to be performed, are planned as follows:
1. st injection: upper part of the upper arm, posterior surface
2. nd injection: upper part of the thigh
3. rd injection: abdomen with the exception of the umbilical area
4. th injection: upper part of the contra-lateral upper arm, posterior surface
5. th injection: upper part of the contra-lateral thigh
6. th injection: abdomen with the exception of the umbilical area
7. th injection: upper part of the same upper arm, posterior surface as for the 1st injection. Receives: Drug: Filgrastim test; Drug: Filgrastim reference |
| Group 3: filgrastim 10 µg/kg/day for 5 consecutive days | Other | The test investigational product is BK0023. The reference product is Neupogen® 30, by Dompé Biotec S.p.A., Italy.
Both study treatments were administered according to a cross-over design in 2 subsequent periods separated by wash-out periods of at least 28 days.
The sites, where the injections are to be performed, are planned as follows:
1. st injection: upper part of the upper arm, posterior surface
2. nd injection: upper part of the thigh
3. rd injection: abdomen with the exception of the umbilical area
4. th injection: upper part of the contra-lateral upper arm, posterior surface
5. th injection: upper part of the contra-lateral thigh. Receives: Drug: Filgrastim test; Drug: Filgrastim reference |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve of absolute neutrophil count (AUCANCday1) and maximum absolute neutrophil count (ANCday1max); AUCANCday1-10 and AUCANCday1-8; ANCday1-10max and ANCday1-8max; AUCday1 and AUCss of filgrastim in serum.
Baseline adjusted AUC of ANC on day 1 after single dose (AUCANCday1) and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day) including the elimination period (AUCANCday1-10 and AUCANCday1-8) and ANCday1max, ANCday1-10max and ANCday1-8max after treatment with filgrastim 0.3 mg/mL by Bio-ker and Neupogen® AUC of serum filgrastim after both single (AUCday1) and multiple dose (AUCss) of filgrastim 0.3 mg/mL by Bio-ker and Neupogen®
Measured: Day 1 after single dose and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day)
Secondary outcomes (1)
Area under the curve of CD34+ cell count (AUCCD34+) and maximum CD34+ cell count (CD34+max); maximum concentrations at steady state (Cssmax), Cmaxday1, time to achieve Cmax (Tmax), t1/2 and clearance of serum filgrastim
Baseline adjusted AUCCD34+ from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day) including the elimination period and CD34+max after treatment with filgrastim 0.3 mg/mL by Bio-ker and Neupogen® Cmax, Tmax t1/2 and clearance of serum filgrastim after both single (Cmaxday1, Tmaxday1, t1/2day1 and Clday1) and multiple dose (Cssmax, Tssmax, tss1/2, Clss) of filgrastim 0.3 mg/mL by Bio-ker and Neupogen®
Measured: On day 1 after single dose and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2013 (estimated)
- Study startJun 2007
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for Healthy Male SubjectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bio-ker S.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A., Nerviano Medical Sciences, AAI Deutschland GmbH & Co. KG, Gife S.A.
- Responsible party
- Sponsor
- Investigators
- Antonio Rusca, MD, Principal investigator, CROSS Research SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01933971
- Sponsor's protocol ID
- CRO-PK-06-175
- Other IDs
- 2007DR1116
- Status last verified
- Sep 2013
- First submitted
- 29 Aug 2013
- Last updated
- 9 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol. 1984 Nov;2(11):1281-8. doi: 10.1200/JCO.1984.2.11.1281. No abstract available.
PubMed 6387060Gardner SN. A mechanistic, predictive model of dose-response curves for cell cycle phase-specific and -nonspecific drugs. Cancer Res. 2000 Mar 1;60(5):1417-25.
PubMed 10728708Skipper HE. Kinetics of mammary tumor cell growth and implications for therapy. Cancer. 1971 Dec;28(6):1479-99. doi: 10.1002/1097-0142(197112)28:63.0.co;2-m. No abstract available.
PubMed 5127796Skipper HE, Schabel FM, Lloyd HH. Dose-response and tumour cell repopulation rate in chemotherapeutic trials. Adv Cancer Chemother 1: 205-253, 1979
Welte K, Platzer E, Lu L, Gabrilove JL, Levi E, Mertelsmann R, Moore MA. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1526-30. doi: 10.1073/pnas.82.5.1526.
PubMed 3871951Nomura H, Imazeki I, Oheda M, Kubota N, Tamura M, Ono M, Ueyama Y, Asano S. Purification and characterization of human granulocyte colony-stimulating factor (G-CSF). EMBO J. 1986 May;5(5):871-6. doi: 10.1002/j.1460-2075.1986.tb04297.x.
PubMed 3487449Simmers RN, Webber LM, Shannon MF, Garson OM, Wong G, Vadas MA, Sutherland GR. Localization of the G-CSF gene on chromosome 17 proximal to the breakpoint in the t(15;17) in acute promyelocytic leukemia. Blood. 1987 Jul;70(1):330-2.
PubMed 2439153Nicola NA. Hemopoietic cell growth factors and their receptors. Annu Rev Biochem. 1989;58:45-77. doi: 10.1146/annurev.bi.58.070189.000401. No abstract available.
PubMed 2549855Nicola NA, Metcalf D, Matsumoto M, Johnson GR. Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem. 1983 Jul 25;258(14):9017-23.
PubMed 6190815Nicola NA, Begley CG, Metcalf D. Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells. Nature. 1985 Apr 18-24;314(6012):625-8. doi: 10.1038/314625a0.
PubMed 2986009Fukunaga R, Ishizaka-Ikeda E, Nagata S. Purification and characterization of the receptor for murine granulocyte colony-stimulating factor. J Biol Chem. 1990 Aug 15;265(23):14008-15.
PubMed 1696260Layton JE, Hall NE, Connell F, Venhorst J, Treutlein HR. Identification of ligand-binding site III on the immunoglobulin-like domain of the granulocyte colony-stimulating factor receptor. J Biol Chem. 2001 Sep 28;276(39):36779-87. doi: 10.1074/jbc.M104787200. Epub 2001 Jul 23.
PubMed 11468284Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y. Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest. 1993 Apr;91(4):1310-3. doi: 10.1172/JCI116330.
PubMed 7682568Boneberg EM, Hareng L, Gantner F, Wendel A, Hartung T. Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-gamma. Blood. 2000 Jan 1;95(1):270-6.
PubMed 10607712Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P, Mantovani A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 1989 Feb 2;337(6206):471-3. doi: 10.1038/337471a0.
PubMed 2464767
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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®
- ClinicalTrials.gov ID
- NCT01933971
- Acronym / sponsor ID
- CRO-PK-06-175
- Conditions
- Healthy Male Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Bio-ker S.r.l.Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A., Nerviano Medical Sciences, AAI Deutschland GmbH & Co. KG, Gife S.A.
- Study start
- Jun 2007
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 4 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 0.3 mg/mL by Bio-Ker S.r.l. vs. the comparator (Neupogen® 0.3 mg/mL, Dompé Biotec S.p.A., Italy). Healthy male subjects will receive test and reference at the doses of 2.5 and 5 µg/kg/day for 7 consecutive days and at the dose of 10 µg/kg/day for 5 consecutive days according to a randomised cross-over design. Pharmacodynamics, pharmacokinetics and safety of BK0023 injectable formulation 0.3 mg/mL and of Neupogen® 0.3 mg/mL, 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, i.e. 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 2.5 and 5 μg/kg/day 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 μg/kg/day 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: filgrastim 2.5 µg/kg/day for 7 consecutive days | Other | Drug: Filgrastim test, Drug: Filgrastim referenceThe test investigational product is BK0023. The reference product is Neupogen® 30, by Dompé Biotec S.p.A., Italy. Both study treatments were administered according to a cross-over design in 2 subsequent periods separated by wash-out periods of at least 28 days. The sites, where the injections are to be performed, are planned as follows: 1. st injection: upper part of the upper arm, posterior surface 2. nd injection: upper part of the thigh 3. rd injection: abdomen with the exception of the umbilical area 4. th injection: upper part of the contra-lateral upper arm, posterior surface 5. th injection: upper part of the contra-lateral thigh 6. th injection: abdomen with the exception of the umbilical area 7. th injection: upper part of the same upper arm, posterior surface as for the 1st injection. |
| Group 2: filgrastim 5 µg/kg/day for 7 consecutive days | Other | Drug: Filgrastim test, Drug: Filgrastim referenceThe test investigational product is BK0023. The reference product is Neupogen® 30, by Dompé Biotec S.p.A., Italy. Both study treatments were administered according to a cross-over design in 2 subsequent periods separated by wash-out periods of at least 28 days. The sites, where the injections are to be performed, are planned as follows: 1. st injection: upper part of the upper arm, posterior surface 2. nd injection: upper part of the thigh 3. rd injection: abdomen with the exception of the umbilical area 4. th injection: upper part of the contra-lateral upper arm, posterior surface 5. th injection: upper part of the contra-lateral thigh 6. th injection: abdomen with the exception of the umbilical area 7. th injection: upper part of the same upper arm, posterior surface as for the 1st injection. |
| Group 3: filgrastim 10 µg/kg/day for 5 consecutive days | Other | Drug: Filgrastim test, Drug: Filgrastim referenceThe test investigational product is BK0023. The reference product is Neupogen® 30, by Dompé Biotec S.p.A., Italy. Both study treatments were administered according to a cross-over design in 2 subsequent periods separated by wash-out periods of at least 28 days. The sites, where the injections are to be performed, are planned as follows: 1. st injection: upper part of the upper arm, posterior surface 2. nd injection: upper part of the thigh 3. rd injection: abdomen with the exception of the umbilical area 4. th injection: upper part of the contra-lateral upper arm, posterior surface 5. th injection: upper part of the contra-lateral thigh. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- a body mass index (BMI) between 18 and 28 kg/m2,
- a body weight between 60 and 90 kg,
- good health based on medical history, physical examination, a 12-lead electrocardiogram (ECG) and routine haematology and blood chemistry tests,
- willingness to provide written informed consent
- values of leukocytes and thrombocytes had to be inside the normality range at the screening.
Key exclusion criteria (3 listed)
- intake of any concomitant medication,
- a history of drug, caffeine (>5 cups coffee/tea/day) or tobacco (>/=10 cigarettes/day) abuse, or alcohol consumption in excess of two drinks per day, as defined by the U.S.D.A. dietary guidelines,
- ascertained or presumptive hypersensitivity to the active compound or history of anaphylaxis to drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Filgrastim testAlso: r-metHuG-CSF, BK00230.3 mg/mL injectable solution in 1 mL vials Manufacturer (Drug Substance): Eurogenetec S.A., B-4102 Seraing, Belgium Manufacturer (Drug Product): Areta International S.r.l., I-21040 Gerenzano, Italy Batch release: Areta International S.r.l., I-21040 Gerenzano, Italy Route of administration: subcutaneous | Drug | Group 1: filgrastim 2.5 µg/kg/day for 7 consecutive days, Group 2: filgrastim 5 µg/kg/day for 7 consecutive days, Group 3: filgrastim 10 µg/kg/day for 5 consecutive days |
| Filgrastim referenceAlso: r-metHuG-CSF, Neupogen®0.3 mg/mL injectable solution in 1 mL vials Licensed owner: Dompé farmaceutici S.p.A., Milan, Italy Manufacturer (Drug Product): Hoffmann - La Roche Ltd., Basel, Switzerland and Amgen Manufacturing Limited, Puertorico. Batch release: Amgen Europe B.V., Breda, Netherlands Route of administration: subcutaneous | Drug | Group 1: filgrastim 2.5 µg/kg/day for 7 consecutive days, Group 2: filgrastim 5 µg/kg/day for 7 consecutive days, Group 3: filgrastim 10 µg/kg/day for 5 consecutive days |
Primary outcome
Area under the curve of absolute neutrophil count (AUCANCday1) and maximum absolute neutrophil count (ANCday1max); AUCANCday1-10 and AUCANCday1-8; ANCday1-10max and ANCday1-8max; AUCday1 and AUCss of filgrastim in serum.
Time frame: Day 1 after single dose and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day)
Baseline adjusted AUC of ANC on day 1 after single dose (AUCANCday1) and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day) including the elimination period (AUCANCday1-10 and AUCANCday1-8) and ANCday1max, ANCday1-10max and ANCday1-8max after treatment with filgrastim 0.3 mg/mL by Bio-ker and Neupogen® AUC of serum filgrastim after both single (AUCday1) and multiple dose (AUCss) of filgrastim 0.3 mg/mL by Bio-ker and Neupogen®
1 secondary outcome
Area under the curve of CD34+ cell count (AUCCD34+) and maximum CD34+ cell count (CD34+max); maximum concentrations at steady state (Cssmax), Cmaxday1, time to achieve Cmax (Tmax), t1/2 and clearance of serum filgrastim
Time frame: On day 1 after single dose and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2013.
- Background: PubMed 6387060Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol. 1984 Nov;2(11):1281-8. doi: 10.1200/JCO.1984.2.11.1281. No abstract available.
- Background: PubMed 10728708Gardner SN. A mechanistic, predictive model of dose-response curves for cell cycle phase-specific and -nonspecific drugs. Cancer Res. 2000 Mar 1;60(5):1417-25.
- Background: PubMed 5127796Skipper HE. Kinetics of mammary tumor cell growth and implications for therapy. Cancer. 1971 Dec;28(6):1479-99. doi: 10.1002/1097-0142(197112)28:63.0.co;2-m. No abstract available.
- BackgroundSkipper HE, Schabel FM, Lloyd HH. Dose-response and tumour cell repopulation rate in chemotherapeutic trials. Adv Cancer Chemother 1: 205-253, 1979
- Background: PubMed 3871951Welte K, Platzer E, Lu L, Gabrilove JL, Levi E, Mertelsmann R, Moore MA. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1526-30. doi: 10.1073/pnas.82.5.1526.
- Background: PubMed 3487449Nomura H, Imazeki I, Oheda M, Kubota N, Tamura M, Ono M, Ueyama Y, Asano S. Purification and characterization of human granulocyte colony-stimulating factor (G-CSF). EMBO J. 1986 May;5(5):871-6. doi: 10.1002/j.1460-2075.1986.tb04297.x.
- Background: PubMed 2439153Simmers RN, Webber LM, Shannon MF, Garson OM, Wong G, Vadas MA, Sutherland GR. Localization of the G-CSF gene on chromosome 17 proximal to the breakpoint in the t(15;17) in acute promyelocytic leukemia. Blood. 1987 Jul;70(1):330-2.
- Background: PubMed 2549855Nicola NA. Hemopoietic cell growth factors and their receptors. Annu Rev Biochem. 1989;58:45-77. doi: 10.1146/annurev.bi.58.070189.000401. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Rusca, MD principal investigator
CROSS Research SA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Filgrastim test and Filgrastim reference in people with Healthy Male Subjects, run by Bio-ker S.r.l. at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the curve of absolute neutrophil count (AUCANCday1) and maximum absolute neutrophil count (ANCday1max); AUCANCday1-10 and AUCANCday1-8; ANCday1-10max and ANCday1-8max; AUCday1 and AUCss of filgrastim in serum. (time frame: Day 1 after single dose and from day 1 to 10 (dose groups of 2.5 and 5 µg/kg/day) or from day 1 to 8 (dose group of 10 µg/kg/day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01933971, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2013.