<br>        Inclusion Criteria:<br><br>          1. Informed consent signed by the subject.<br><br>          2. Healthy male and female subjects aged 18 to 55 years of any ethnic origin.<br><br>          3. Physically and mentally healthy subjects as confirmed by an interview, medical<br>             history, clinical examination, laboratory tests and ECG. Values out of reference<br>             range have to be assessed as not clinically significant (NCS) or clinically<br>             significant (CS) by the investigator. Individuals presenting deviating values<br>             assessed as not clinically significant may be included.<br><br>          4. Male subjects willing to use contraceptive methods from the time of dosing until 3<br>             months after study drug administration (such as condom or occlusive cap (diaphragm or<br>             cervical/vault caps) with spermicidal foam/gel/film/cream/suppository), females must<br>             be of non-childbearing potential. Non-childbearing potential is defined as follows:<br>             Female subjects must be surgically sterile or post-menopausal (defined as at least<br>             two years post cessation of menses and follicular stimulating hormone = 35 mIU/mL and<br>             serum estradiol =25 pg/mL), non-lactating and have a negative pregnancy test.<br><br>          5. Body mass index between 19 and 29 kg/m2 (extremes included).<br><br>          6. Body weight between 50 and 100 kg (extremes included).<br><br>          7. Calculated creatinine clearance = 90 mL/min according to the Cockcroft-Gault-formula.<br><br>          8. Normal lung function (FVC and FEV1 at least 80% of predicted values) at screening.<br><br>          9. O2 saturation between 96% and 100% (extremes included) at screening.<br><br>         10. The subject is co-operative and available for the entire study.<br><br>        Exclusion Criteria:<br><br>          1. Evidence in the subject's medical history or in the medical examination of any<br>             clinically significant hepatic, renal, gastrointestinal, cardiovascular, pulmonary,<br>             hematological or other significant acute or chronic abnormalities which might<br>             influence either the safety of the subject or the absorption, distribution,<br>             metabolism or excretion of the active agent under investigation.<br><br>          2. History of general malignant diseases.<br><br>          3. History of renal calculus.<br><br>          4. Hypersensitivity to drugs, atopic eczema, allergic bronchial asthma or any clinically<br>             significant allergic disease (excluding non-active hayfever).<br><br>          5. Hypersensitivity to the active substances or to any of its excipients.<br><br>          6. Subjects having already received G-CSF in the past.<br><br>          7. Intake of vitamin A derivates or retinoids within 30 days prior to the start of study<br>             drug administration.<br><br>          8. Subjects who have a significant history of sensitivity to natural sunlight or<br>             artificial light such as ultraviolet (UV) light from sunbeds.<br><br>          9. History of thrombosis or increased bleeding risk.<br><br>         10. Laboratory test results outside the reference values as laid down by the study<br>             center, which may be an evidence of disease. Positive result of HIV1/2, HCV antibody<br>             or HBs antigen testing.<br><br>         11. Subjects who have an abnormality in the 12-lead ECG that, in the opinion of the<br>             investigator, increases the risk of participating in the study, such as QTcB interval<br>             >450 msec (females) and >430 msec (males), 2nd or 3rd degree atrioventricular block,<br>             complete left bundle branch block, complete right bundle branch block or<br>             Wolff-Parkinson-White Syndrome, defined as PR<110 msec, confirmed by a repeated ECG.<br><br>         12. Subjects who have had a clinically significant illness within 8 weeks prior to the<br>             start of study drug administration as determined by the investigator.<br><br>         13. History of relevant heart disorders or evidence of hyper- or hypotension (supine<br>             blood pressure systolic >140 mmHg or <95 mmHg or diastolic >90 mmHg or <65 mmHg at<br>             screening).<br><br>         14. Bradycardia or bradyarrhythmia (heart rate after 3 minutes supine rest <45/min at<br>             screening).<br><br>         15. Tachycardia or Tachyarrhythmia (heart rate after 3 minutes supine rest >90/min at<br>             screening).<br><br>         16. Chronic infection or acute infection or fever within the last 8 weeks prior to the<br>             start of study drug administration as determined by the investigator.<br><br>         17. Subjects who have received any prescribed systemic or topical medication within 14<br>             days prior to dose administration as stated by the subject at screening, unless the<br>             medication will not interfere with the study procedures or compromise safety as<br>             assessed by an investigator in consultation with the sponsor.<br><br>         18. Subjects who have received any medications (including St John's Wort) known to<br>             chronically alter drug absorption or elimination processes within 30 days prior to<br>             study drug administration as stated by the subject at screening, unless the<br>             medication will not interfere with the study procedures or compromise safety as<br>             assessed by an investigator in consultation with the sponsor.<br><br>         19. Single use of any medication (including OTC) that are not expressively permitted<br>             within two weeks prior to scheduled admission to the study (self-medication or<br>             prescription) as stated by the subject at screening, unless the medication will not<br>             interfere with the study procedures or compromise safety as assessed by an<br>             investigator in consultation with the sponsor.<br><br>         20. Abuse of alcohol (equivalent to more than 18 units per week, where 1 unit is<br>             equivalent to one beer (about 330 ml) or one wine (about 150 ml) or one drink (about<br>             40 ml)), caffeine (equivalent to more than 750 mg per day) or tobacco (equivalent to<br>             more than 10 cigarettes a day).<br><br>         21. Alcohol breath test positive at screening.<br><br>         22. Drug addiction, positive drug screening in urine.<br><br>         23. Participation in another clinical investigation or being in the restriction period<br>             after a clinical investigation.<br><br>         24. Blood donation of more than 100 ml or a comparable blood loss within three months<br>             prior to study drug administration.<br><br>         25. Subjects who are known or suspected (i) not to comply with the study directives, (ii)<br>             not to be reliable or trustworthy, (iii) not to be capable of understanding and<br>             evaluating the information given to them as part of the formal information policy<br>             (informed consent), in particular regarding the risks and discomfort to which they<br>             would agree to be exposed to, or (iv) to be in such a precarious financial situation<br>             that they no longer weigh up the possible risks of their participation and the<br>             unpleasantness they may be involved in.<br><br>         26. Subjects with inadequate venous access.<br><br>         27. Subjects who, in the opinion of the investigator, should not participate in the<br>             study.<br><br>         28. Subjects with an abnormal splenic size.<br>