Comparative Immunogenicity Study of Multiple Doses of Proposed Pegfilgrastim Biosimilar, INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects.

• Sponsor: Intas Pharmaceuticals, Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04015232
• Collaborator: Lambda Therapeutic Research Ltd. (Industry)
• Enrollment: 200
• Location: 1
• Arms: 2
• Actual Duration (Months): 3.3
• Patients Per Site Per Month: 61.5

Study Details

Study Description

Brief Summary

The study was an assessor-blind, balanced, parallel, randomized, two-treatment, comparative immunogenicity study of multiple doses of subcutaneous (SC) Pegfilgrastim injection (6 mg/0.6 mL; Intas Pharmaceuticals Ltd. proposed biosimilar INTP5 compared to innovator product, US-Neulasta) in healthy, adult, human subjects under fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Immunogenicity; Healthy Volunteers	Combination Product: INTP5; Combination Product: US Neulasta	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: The study staff taking care of subject's safety and the laboratory personnel doing the sample analysis of PK, PD, and immunogenicity data were blinded
• Primary Purpose: Other
• Official Title: An Assessor-blind, Balanced, Parallel, Randomized, Two-treatment, Comparative Immunogenicity Study of Multiple Doses of INTP5 of Intas Pharmaceuticals Limited, India Against Neulasta® of Amgen Inc., USA Administered Subcutaneously in Healthy, Adult, Human Subjects Under Fed Condition.
• Actual Study Start Date: Feb 26, 2018
• Actual Primary Completion Date: Jun 5, 2018
• Actual Study Completion Date: Jun 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INTP5 biosimilar product INTP5 subcutaneously at a dose of 6 mg/0.6 mL.	Combination Product: INTP5; INTP5, a pegfilgrastim biosimilar to US Neulasta.
Active Comparator: US Neulasta reference product US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.	Combination Product: US Neulasta; US Neulasta: FDA approved pegfilgrastim innovator product.

Outcome Measures

Primary Outcome Measures

1. Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. [Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose.]

   Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: Screening assay to assess if samples were positive or negative for anti-PegG-CSF. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity.

Secondary Outcome Measures

1. PK Endpoints: Pegfilgrastim C[Max] [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   Pharmacokinetic (PK) properties of the test and reference formulations were assessed by measuring serum Pegfilgrastim concentration. Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.

2. PK Endpoints: Pegfilgrastim AUC[0-t] [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   Area under the serum concentration vs. time curve, calculated by linear trapezoidal rule from measured data points from the time zero to the time of last quantified concentration.

3. PK Endpoints: Pegfilgrastim AUC[0-∞] [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   Area under the serum concentration versus time curve from time zero to infinity. Where AUC[0-infinity]= AUC[0-t] + Ct/lambda-z, Ct is the last measurable concentration and lamda-z is the terminal rate constant. AUC[0-infinity] is the sum of measurable and extrapolated parts.

4. PK Endpoints: Pegfilgrastim T[Max] [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.

5. PK Endpoints: Pegfilgrastim λz (Lambda-z) [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   Terminal rate constant: First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more nonzero plasma concentration values.

6. PK Endpoints: Pegfilgrastim R^2 Adjusted [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz (lambda-z). R^2 is the coefficient of determination and can range from 0 to 1, with higher values indicating greater predictability.

7. PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   The residual area in percentage determined by the formula, [(AUC[0-infinity]-AUC[0-t])/AUC[0-infinity]] x 100.

8. PK Endpoints: Pegfilgrastim t[1/2] [Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.]

   The terminal half-life calculated using the formula 0.693/(lambda-z)

9. PD Endpoints for Baseline Non-adjusted ANC: E[Max] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

   Maximum measured absolute neutrophil count (ANC).

10. PD Endpoints for Baseline Non-adjusted ANC: T[Max] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    Area under the ANC versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.

11. PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    Time to reach the maximum measured absolute neutrophil count (ANC)

12. PD Endpoints for Baseline Adjusted ANC: E[Max] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    Maximum measured absolute neutrophil count (ANC).

13. PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.

14. PD Endpoints for Baseline Adjusted ANC: T[Max] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    Time to reach the maximum measured absolute neutrophil count (ANC)

15. PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more non-zero plasma concentration values.

16. PD Endpoints for Baseline Adjusted ANC: t[1/2] [Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.]

    The terminal half-life will be calculated as 0.693/(lambda-z)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. Normal, healthy adult human volunteers between 18 to 45 years of age (both inclusive) living in and around Ahmedabad city or western part of India.

2. Having body weight ≥50 kg and body mass index (BMI) between 18.5 and 29.9 (both inclusive), calculated as weight in kg/height in meter^2.

3. Not having any significant disease in medical history or clinically significant abnormal findings during screening, abdominal ultrasonography, medical history, clinical examination, laboratory evaluations, 12-lead echocardiogram (ECG) and chest X-ray (posterior-anterior view; within the last 6 months) recordings.

4. Able to understand and comply with the study procedures, in the opinion of the investigator.

5. Able to give voluntary written informed consent for participation in the trial.

6. In case of female subjects:

• Surgically sterilized at least 6 months prior to study participation; Or If a woman of child bearing potential is willing to use a suitable and effective double barrier contraceptive method or intra uterine device during the study.

• Serum pregnancy test (for female subjects) must be negative.

Exclusion criteria:

1. Known hypersensitivity to the study drug or its constituents and/or hypersensitivity to E. coli derived proteins, and/or previous exposure to the study drug.

2. History or presence of any disease or condition which might compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.

3. Known case of hereditary fructose intolerance.

4. Subjects with latex allergies will be excluded as the needle cover on the single-use prefilled syringe contains dry natural rubber (latex).

5. Any clinically significant laboratory finding including absolute neutrophil count (ANC), platelet, red blood cells (RBC) count, and hemoglobin level at the time of screening.

6. Prior exposure to any peptide colony stimulating or growth factor, including erythropoietin, filgrastim or Pegfilgrastim; Prior exposure to any vaccines, immunoglobulin preparations or immunomodulators within the past 6 months prior to receiving first dose; evidence of E. coli diarrhea or diseases within 3 months.

7. Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or NSAIDs induced urticaria.

8. Subjects with a history of pulmonary infiltrate or pneumonia in the last 6 months.

9. History of any hematologic disease including sickle cell disorders.

10. Ingestion or use of any prescribed medication at any time within 1 month prior to receiving first dose.

11. Receipt of over-the-counter medicines which have not yet cleared from the body (5 half-lives must have passed for the medicine to be considered to have cleared from the body).

12. A recent history of harmful use of alcohol, i.e. alcohol consumption of more than 14 standard drinks per week for men and more than 7 standard drinks per week for women (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy etc.) or consumption of alcohol or alcoholic products within 72 hours prior to receiving study medicine.

13. Smokers, who smoke 10 or more than 10 cigarettes/day or inability to abstain from smoking during the study.

14. Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.

15. Donation of blood (1 unit or 350 mL) or equivalent amount of blood substitute.

16. Receipt of an investigational medicinal product or participation in a drug research study within a period of 90 days prior to the first dose of study medication. Elimination half-life of the study drug should be taken into consideration for inclusion of the subject in the study.

17. Positive result for human immunodeficiency virus (HIV I &/or II) and/or hepatitis B and C tests.

18. History or presence of cancer because of which anticipated life span is less than 5 years as per the investigator's assessment.

19. History or presence of psychiatric disorders.

20. Presence of tattoo or scars or any type of skin lesions due to infection, burning, wound or inflammation at the proposed site of injection.

21. An unusual diet, for whatever reason (e.g. low-sodium), for 4 weeks prior to receiving the study medicine. In any such case, subject selection will be at the discretion of the Principal Investigator.

22. Consumption of grape fruit or grape fruit products within 72 hours prior to receiving study drug.

23. A history of difficulty in donating blood.

24. Females, pregnant or lactating, or planning to become pregnant during the time the subject is on study or found positive in pregnancy test at screening.

25. Any infections in the last 4 weeks before receiving study medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lambda Therapeutic Research Ltd.	Ahmedabad	Gota	India	382481

Sponsors and Collaborators

• Intas Pharmaceuticals, Ltd.
• Lambda Therapeutic Research Ltd.

Investigators

• Principal Investigator: Adarsh K Garg, M.B.B.S, Lambda Therapeutic Research Ltd.
• Study Director: Vinu Jose, M.D., Intas Pharmaceuticals, Ltd.

Study Documents (Full-Text)

• Study Protocol - Jan 22, 2018
• Statistical Analysis Plan - Jun 27, 2018

More Information

Publications

None provided.

• Responsible Party: Intas Pharmaceuticals, Ltd.
• ClinicalTrials.gov Identifier: NCT04015232
• Other Study ID Numbers: 0554-17
• First Posted: Jul 10, 2019
• Last Update Posted: Oct 4, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Intas Pharmaceuticals, Ltd.: Pegfilgrastim; Biosimilar; Immunogenicity; Pharmacokinetics; Pharmacodynamics; Safety; Healthy Volunteers

Study Results

Participant Flow

Arm/Group Title	INTP5 Biosimilar Product	US Neulasta Reference Product
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Period Title: Overall Study
STARTED	100	100
COMPLETED	89	93
NOT COMPLETED	11	7

Baseline Characteristics

Arm/Group Title	INTP5 Biosimilar Product	US Neulasta Reference Product	Total
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	Total of all reporting groups
Overall Participants	100	100	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.5 (6.82)	34.3 (6.05)	32.9 (6.58)
Sex: Female, Male (Count of Participants)
Female	40 40%	40 40%	80 40%
Male	60 60%	60 60%	120 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	100 100%	100 100%	200 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
India	100 100%	100 100%	200 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	160.2 (8.48)	160.1 (8.68)	160.2 (8.56)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	61.3 (8.31)	62.6 (7.49)	61.9 (7.92)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.95 (3.069)	24.51 (3.266)	24.23 (3.173)

Outcome Measures

1. Primary Outcome

Title	Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies.
Description	Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: Screening assay to assess if samples were positive or negative for anti-PegG-CSF. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity.
Time Frame	Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	INTP5 Biosimilar Product	US Neulasta Reference Product
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	94	100
Positive for Anti-Drug-Antibody	10 10%	9 9%
Positive in Neutralizing Anti-Drug-Antibody	0 0%	0 0%
No Anit-Drug Antibody Confirmed Positive Results	84 84%	91 91%

2. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim C[Max]
Description	Pharmacokinetic (PK) properties of the test and reference formulations were assessed by measuring serum Pegfilgrastim concentration. Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta.

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [ng/mL]	483.230 (175.1787)	346.018 (150.4879)	368.569 (223.3380)	371.778 (263.4440)

3. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim AUC[0-t]
Description	Area under the serum concentration vs. time curve, calculated by linear trapezoidal rule from measured data points from the time zero to the time of last quantified concentration.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [ng.h/mL]	22417.938 (9922.2648)	13640.695 (6709.2752)	16610.870 (11255.1296)	15255.327 (11050.7580)

4. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim AUC[0-∞]
Description	Area under the serum concentration versus time curve from time zero to infinity. Where AUC[0-infinity]= AUC[0-t] + Ct/lambda-z, Ct is the last measurable concentration and lamda-z is the terminal rate constant. AUC[0-infinity] is the sum of measurable and extrapolated parts.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [ng.h/mL]	22436.497 (9922.4383)	13637.403 (6699.9736)	16630.861 (11253.7406)	15280.376 (11058.1142)

5. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim T[Max]
Description	The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [h]	22.405 (3.3758)	20.800 (5.5936)	22.226 (3.5298)	23.111 (2.6667)

6. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim λz (Lambda-z)
Description	Terminal rate constant: First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more nonzero plasma concentration values.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [1/h]	0.021 (0.0071)	0.025 (0.0142)	0.022 (0.0058)	0.019 (0.0074)

7. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim R^2 Adjusted
Description	Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz (lambda-z). R^2 is the coefficient of determination and can range from 0 to 1, with higher values indicating greater predictability.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [Coefficient of Determination]	0.968 (0.0379)	0.876 (0.133)	0.974 (0.0245)	0.879 (0.2339)

8. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs]
Description	The residual area in percentage determined by the formula, [(AUC[0-infinity]-AUC[0-t])/AUC[0-infinity]] x 100.
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [percentage of AUC]	0.115 (0.1106)	0.644 (1.4428)	0.230 (0.2672)	0.266 (0.2664)

9. Secondary Outcome

Title	PK Endpoints: Pegfilgrastim t[1/2]
Description	The terminal half-life calculated using the formula 0.693/(lambda-z)
Time Frame	Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Outcome Measure Data

Analysis Population Description

All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	10	10	9	9
Mean (Standard Deviation) [h]	36.721 (11.0052)	36.612 (19.6215)	34.172 (8.8669)	40.616 (14.6054)

10. Secondary Outcome

Title	PD Endpoints for Baseline Non-adjusted ANC: E[Max]
Description	Maximum measured absolute neutrophil count (ANC).
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	89	89	93	93
ADA-NEGATIVE	40.72 (10.862)	44.63 (11.077)	38.34 (9.925)	40.62 (8.963)
ADA-POSITIVE	42.89 (10.512)	46.53 (9.093)	38.38 (8.211)	44.96 (16.409)

11. Secondary Outcome

Title	PD Endpoints for Baseline Non-adjusted ANC: T[Max]
Description	Area under the ANC versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	89	89	93	93
ADA-NEGATIVE	64.710 (11.1076)	59.587 (14.9170)	63.182 (15.8763)	64.637 (20.5772)
ADA-POSITIVE	72.003 (0.0072)	67.453 (15.7091)	64.002 (12.0014)	61.461 (29.9401)

12. Secondary Outcome

Title	PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t]
Description	Time to reach the maximum measured absolute neutrophil count (ANC)
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Table breaks participants into ADA(-) or ADA(+), totaling the overall number of participants by arm. 5 Subjects having three consecutive missing samples in elimination phase were excluded from the analysis of AUEC0-t reducing the total participants to 88 for INTP5 Dose 1, 88 for INTP5 Dose 2, 92 for Neulasta Dose 1, and 91 for Neulasta Dose 2.

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	88	88	92	91
ADA-NEGATIVE	7107.14 (1481.971)	7929.25 (1561.246)	6718.70 (1361.957)	7359.09 (1455.570)
ADA-POSITIVE	7286.53 (1744.737)	8539.99 (1522.935)	6846.77 (763.675)	7761.65 (1658.478)

13. Secondary Outcome

Title	PD Endpoints for Baseline Adjusted ANC: E[Max]
Description	Maximum measured absolute neutrophil count (ANC).
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	88	88	91	89
ADA-NEGATIVE	36.50 (10.458)	40.80 (11.038)	33.35 (9.189)	36.56 (8.755)
ADA-POSITIVE	38.37 (9.548)	42.50 (10.061)	34.18 (8.503)	40.76 (17.170)

14. Secondary Outcome

Title	PD Endpoints for Baseline Adjusted ANC: AUEC[0-t]
Description	Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	87	87	90	89
ADA-NEGATIVE	4920.26 (1339.674)	5992.49 (1555.062)	4389.55 (1140.655)	5441.01 (1478.241)
ADA-POSITIVE	4967.86 (1229.792)	6539.58 (2202.473)	4578.32 (1200.125)	5676.92 (1991.456)

15. Secondary Outcome

Title	PD Endpoints for Baseline Adjusted ANC: T[Max]
Description	Time to reach the maximum measured absolute neutrophil count (ANC)
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	88	88	91	91
ADA-NEGATIVE	64.617 (11.1482)	59.735 (14.9546)	65.553 (15.8887)	65.043 (20.6610)
ADA-POSITIVE	72.003 (0.0072)	67.453 (15.7091)	64.002 (12.0014)	61.461 (29.9401)

16. Secondary Outcome

Title	PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z)
Description	First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more non-zero plasma concentration values.
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	86	87	89	88
ADA-NEGATIVE	0.01 (0.007)	0.01 (0.006)	0.01 (0.006)	0.01 (0.006)
ADA-POSITIVE	0.01 (0.006)	0.01 (0.003)	0.01 (0.004)	0.01 (0.005)

17. Secondary Outcome

Title	PD Endpoints for Baseline Adjusted ANC: t[1/2]
Description	The terminal half-life will be calculated as 0.693/(lambda-z)
Time Frame	Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.

Outcome Measure Data

Analysis Population Description

Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm

Arm/Group Title	INTP5 Dose 1	INTP5 Dose 2	US Neulasta Dose 1	US Neulasta Dose 2
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.	US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
Measure Participants	86	87	89	88
ADA-NEGATIVE	62.25 (28.847)	64.13 (26.785)	77.23 (86.239)	76.02 (59.888)
ADA-POSITIVE	67.03 (41.296)	69.72 (25.447)	81.74 (29.981)	67.02 (22.706)

Adverse Events

Time Frame	99 Days
Arm/Group Title	INTP5 Biosimilar Product		US Neulasta Reference Product
Arm/Group Description	INTP5 subcutaneously at a dose of 6 mg/0.6 mL. INTP5: A pegfilgrastim biosimilar to US Neulasta.		US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta: FDA approved pegfilgrastim innovator product.
All Cause Mortality
	INTP5 Biosimilar Product		US Neulasta Reference Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		1/100 (1%)
Serious Adverse Events
	INTP5 Biosimilar Product		US Neulasta Reference Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		1/100 (1%)
General disorders
death	0/100 (0%)	0	1/100 (1%)	1
Other (Not Including Serious) Adverse Events
	INTP5 Biosimilar Product		US Neulasta Reference Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/100 (32%)		37/100 (37%)
Blood and lymphatic system disorders
Eosinophilia	1/100 (1%)	1	0/100 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/100 (1%)	1	0/100 (0%)	0
Diarrhoea	0/100 (0%)	0	2/100 (2%)	2
Gastritis	1/100 (1%)	1	0/100 (0%)	0
Toothache	1/100 (1%)	1	0/100 (0%)	0
Vomiting	5/100 (5%)	7	5/100 (5%)	7
General disorders
Chills	1/100 (1%)	1	0/100 (0%)	0
Injection site pain	5/100 (5%)	5	4/100 (4%)	4
Pyrexia	2/100 (2%)	2	0/100 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	1/100 (1%)	1	1/100 (1%)	1
Injury, poisoning and procedural complications
Face injury	1/100 (1%)	1	0/100 (0%)	0
Injury	0/100 (0%)	0	3/100 (3%)	3
Investigations
Eosinophil count increased	1/100 (1%)	1	0/100 (0%)	0
Hepatic enzyme increased	0/100 (0%)	0	1/100 (1%)	1
Human chorionic gonadotropin increased	0/100 (0%)	0	1/100 (1%)	1
Protein urine present	1/100 (1%)	1	1/100 (1%)	1
Red blood cells urine positive	3/100 (3%)	3	0/100 (0%)	0
Urine analysis abnormal	0/100 (0%)	0	1/100 (1%)	1
Urine output decreased	1/100 (1%)	1	0/100 (0%)	0
Urine abnormality	1/100 (1%)	1	0/100 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	16/100 (16%)	17	15/100 (15%)	16
Nervous system disorders
Headache	6/100 (6%)	7	13/100 (13%)	13
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/100 (1%)	1	0/100 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	1/100 (1%)	1	1/100 (1%)	1
Pruritus	0/100 (0%)	0	1/100 (1%)	1
Rash generalized	0/100 (0%)	0	1/100 (1%)	1
Skin burning sensation	0/100 (0%)	0	1/100 (1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.