A Comparative, Crossover, Pharmacokinetic, Pharmacodynamic and Safety Study of Three Forms of PEG-G-CSF in Normal Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a comparative pharmacokinetic, pharmacodynamic and safety study in healthy volunteers with three forms of pegylated granulocyte colony stimulating factors.

Conditions
-----------------
Pharmacokinetics

Intervention / Treatment
-----------------
* Biological: DRL_PG
* Biological: Pegfilgrastim Form A
* Biological: Pegfilgrastim Form B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and female subjects aged 18 to 55 years A standardized body mass index General good health as determined by the Investigator Normal organ function as per the Investigator's judgement Must be non-smokers, or ex-smokers who have not smoked within the previous 6 months from the screening visit Female subjects must: Not be lactating; not be pregnant Agree to use an acceptable contraceptive method or be of non-childbearing potential Male subjects must refrain from donating sperm or fathering a child during the study and until 3 months after the last study drug Exclusion Criteria: Known hypersensitivity to Escherichia coli derived proteins, pegfilgrastim, filgrastim or any other related component Presence of antibodies to polyethylene glycol at screening Positive result for cotinine (>500 ng/mL) or drugs of abuse at screening or on admission Prior history of or current alcohol abuse or excessive intake of alcohol as judged by the Investigator Donation of blood (≥500 mL) or plasma within the previous 3 months History of unexplained syncopal episodes; Any disorder that, in the Investigator's opinion, may interfere with study compliance History of any cancer History of pulmonary infiltrate or pneumonia within the previous 6 months from screening visit Hereditary fructose and/or sorbitol intolerance Absolute neutrophil count below 1500/mm3 or above 12000/mm3 at screening Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) 1 or 2 Any abnormality in 12-lead ECG that in the Investigator's opinion is clinically significant and/or suggestive of underlying cardiac abnormalities A clinical diagnosis of hypertension, significant hypercholesterolemia as judged by the Investigator, or thyroid abnormalities Family history of acute myeloid leukemia or subjects with splenomegaly at baseline, or with sickle cell disease Any prescribed or over the counter medications including analgesics, herbal remedies, vitamin therapy must not be used from 7 days prior to the first administration of study drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence I (DRL, A, B)<br>Patients will receive study drugs in the following cross-over sequence: DRL_PG, Pegfilgrastim Form A, Pegfilgrastim Form B. Each drug is administered as a single, 6 mg, subcutaneous injection. | Biological: DRL_PG<br> <br> Biological: Pegfilgrastim Form A<br> <br> Biological: Pegfilgrastim Form B<br> <br> |
| Experimental: Treatment Sequence II (DRL, B, A)<br>Patients will receive study drugs in the following cross-over sequence: DRL_PG, Pegfilgrastim Form B, Pegfilgrastim Form A. Each drug is administered as a single, 6 mg, subcutaneous injection. | Biological: DRL_PG<br> <br> Biological: Pegfilgrastim Form A<br> <br> Biological: Pegfilgrastim Form B<br> <br> |
| Experimental: Treatment Sequence III (A, DRL, B)<br>Patients will receive study drugs in the following cross-over sequence: Pegfilgrastim Form A, DRL_PG, Pegfilgrastim Form B. Each drug is administered as a single, 6 mg, subcutaneous injection. | Biological: DRL_PG<br> <br> Biological: Pegfilgrastim Form A<br> <br> Biological: Pegfilgrastim Form B<br> <br> |
| Experimental: Treatment Sequence IV (A, B, DRL)<br>Patients will receive study drugs in the following cross-over sequence: Pegfilgrastim Form A, Pegfilgrastim Form B, DRL_PG. Each drug is administered as a single, 6 mg, subcutaneous injection. | Biological: DRL_PG<br> <br> Biological: Pegfilgrastim Form A<br> <br> Biological: Pegfilgrastim Form B<br> <br> |
| Experimental: Treatment Sequence V (B, A, DRL)<br>Patients will receive study drugs in the following cross-over sequence: Pegfilgrastim Form B, Pegfilgrastim Form A, DRL_PG. Each drug is administered as a single, 6 mg, subcutaneous injection. | Biological: DRL_PG<br> <br> Biological: Pegfilgrastim Form A<br> <br> Biological: Pegfilgrastim Form B<br> <br> |
| Experimental: Treatment Sequence VI (B, DRL, A)<br>Patients will receive study drugs in the following cross-over sequence: Pegfilgrastim Form B, DRL_PG, Pegfilgrastim Form A. Each drug is administered as a single, 6 mg, subcutaneous injection. | Biological: DRL_PG<br> <br> Biological: Pegfilgrastim Form A<br> <br> Biological: Pegfilgrastim Form B<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum plasma concentration | 105 days | 
| AUC(0-inf) | Area under concentration-time curve extrapolated from time 0 to infinity | 105 days | 
| AUC(0-t) | Area under concentration-time curve from time 0 to the time of the last quantifiable concentration | 105 days | 
| Emax | Maximum observed effect | 105 days | 
| AUEC(0-t) | Area under the effect time curve from time zero (predose) to last measured time | 105 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pegfilgrastim, Pharmacokinetics, Pharmacodynamics, Healthy volunteers