Comparative, Pharmacokinetic and Pharmacodynamic Study of Subcutaneous Injections of INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects.

An Assessor-blind, Balanced, Randomized, Two-treatment, Two-period, Single-dose, Two-way, Crossover, Comparative, Pharmacokinetic and Pharmacodynamic Study of Subcutaneous Injections of INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects Under Fed Condition.

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04014062

Enrollment

144

Registered

2019-07-10

Start date

2018-02-12

Completion date

2018-05-01

Last updated

2019-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pharmacokinetic Bioequivalence Study in Human Healthy Volunteers

Keywords

Pegfilgrastim, Biosimilar, Bioequivalence, Pharmacokinetics, Pharmacodynamics, Safety, Healthy Volunteers

Brief summary

The study was an assessor-blind, balanced, randomized, two-treatment, two-period, single-dose, two-way crossover, comparative, pharmacokinetic (PK) and pharmacodynamic (PD) study of subcutaneous (SC) Pegfilgrastim injection (6 mg/0.6 mL; INTP5 and US-Neulasta) in healthy, adult, human subjects under fed conditions.

Interventions

COMBINATION_PRODUCTINTP5

INTP5: A proposed pegfilgrastim biosimilar to US Neulasta.

COMBINATION_PRODUCTUS Neulasta

US Neulasta: FDA-approved pegfilgrastim innovator product.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

SINGLE (Outcomes Assessor)

Masking description

The study staff taking care of subject's safety and the laboratory personnel doing the sample analysis of pharmacokinetic, pharmacodynamic and immunogenicity data are blinded.

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

Inclusion criteria

1. Normal, healthy adult human volunteers between 18 and 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 ECG and chest X-ray (posterior-anterior view; within the last 6 months) recordings. 4. Volunteer who is a Non-smoker 5. Able to understand and comply with the study procedures, in the opinion of the investigator. 6. Able to give voluntary written informed consent for participation in the trial. 7. In case of female subjects: * Surgically sterilized at least 6 months prior to study participation;- Or - If a woman of childbearing 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 pre-filled syringe contains dry natural rubber (latex). 5. Any clinically significant laboratory finding including ANC, platelet, RBC count or 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 vaccines, immunoglobulin preparations, or immunomodulator's within the past 6 months prior to receiving the 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. Smokers, or who have smoked within last six months prior to start of the study. 11. Ingestion or use of any prescribed medication at any time within 1 month prior to receiving first dose in Period-I. 12. 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). 13. 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 in Period-I. 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. Receipt of an investigational medicinal product or participation in a drug research study within a period of 180 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. 16. Positive result for human immunodeficiency virus (HIV I &/or II) and/or hepatitis B and C tests. 17. History or presence of cancer because of which anticipated life span is less than 5 years as per the investigator's assessment. 18. History or presence of psychiatric disorders. 19. Presence of tattoo or scars or any type of skin lesions due to infection, burning, wound or inflammation at the proposed site of injection. 20. An unusual diet, for whatever reason (e.g. low-sodium), for 4 weeks prior to receiving the study medicine in Period-I. In any such case, subject selection will be at the discretion of the Principal Investigator. 21. Consumption of grape fruit or grape fruit products within 72 hours prior to receiving study drug in Period-I. 22. A history of difficulty in donating blood. 23. Females, pregnant or lactating, or planning to become pregnant during the course of the study or found positive in pregnancy test at screening. 24. Any infections in the last 4 weeks before receiving study medication in Period-I.

Design outcomes

Primary

Measure	Time frame	Description
Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	Area under the serum concentration versus time curve from time zero to infinity. Where AUC\[0-infinity\]= AUC\[0-t\] + Ct/λz(lambda-z), Ct is the last measurable concentration and λz(lambda-z) is the terminal rate constant.
Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	Maximum measured absolute neutrophil count (ANC).

Secondary

Measure	Time frame	Description
PK Endpoint: Pegfilgrastim R^2 Adjusted	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz. R\^2 is the coefficient of Determination and can range from 0 to 1,; with higher values indicating greater predictability.
PK Endpoint: Pegfilgrastim t[1/2]	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	The terminal half-life calculated using the formula 0.693/λz(lambda-z).
PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\]0-t\])/AUC0-infinity\] x 100.
PD Endpoint: T[Max] for Baseline Non-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	Time to reach the maximum measured absolute neutrophil count (ANC)
PD Endpoint: AUEC[0-t], Baseline-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
PD Endpoint: T[Max], Baseline-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	Time to reach the maximum measured absolute neutrophil count (ANC)
PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	First order rate constant associated with the terminal (log-linear) portion of the curve. This is estimated via linear regression of time vs. log concentration. This parameter will be calculated by linear least squares regression analysis using at least last three or more non-zero values.
PD Endpoint: t[1/2] for Baseline-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	The terminal half-life will be calculated as 0.693/λz(lamda-z).
PD Endpoint: E[Max], Baseline-adjusted ANC	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.	Maximum measured absolute neutrophil count (ANC)
PK Endpoint: Pegfilgrastim AUC[0-t]	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	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.
PK Endpoint: Pegfilgrastim T[Max]	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.
PK Endpoint: Pegfilgrastim λz(Lambda-z)	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.	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.

Other

Measure	Time frame	Description
Immunogenicity: Presence of Anti-drug Antibodies	0-71 Days	Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. 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. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. 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.

Countries

India

Participant flow

Pre-assignment details

A total of 144 subjects were planned and enrolled. Of these 144, 2 subjects withdrew before dosing. Hence, 142 subjects started the study, were dosed, and were considered for the study analyses.

Participants by arm

Arm	Count
INTP5 Period I, US Neulasta Period II Crossover Period I: Subjects received a single dose of INTP5 subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of US Neulasta. INTP5: INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: US Neulasta: FDA-approved pegfilgrastim innovator product.	71
US Neulasta Period I, INTP5 Period II Crossover Period I: Subjects received a single dose US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of INTP5. INTP5: INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: US Neulasta: FDA-approved pegfilgrastim innovator product.	71
Total	142

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period I: Dosing	Medical Grounds	4	5
Period I: Dosing	Withdrawal by Subject	3	1

Baseline characteristics

Characteristic	US Neulasta Period I, INTP5 Period II Crossover	Total	INTP5 Period I, US Neulasta Period II Crossover
Age, Continuous	32.5 years STANDARD_DEVIATION 6.38	33.6 years STANDARD_DEVIATION 6.15	34.7 years STANDARD_DEVIATION 5.74
BMI	24.32 kg/m^2 STANDARD_DEVIATION 3.188	24.04 kg/m^2 STANDARD_DEVIATION 2.996	23.77 kg/m^2 STANDARD_DEVIATION 2.788
Height	159.3 cm STANDARD_DEVIATION 9	159.2 cm STANDARD_DEVIATION 8.48	159.1 cm STANDARD_DEVIATION 7.99
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	71 Participants	142 Participants	71 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Region of Enrollment India	71 participants	142 participants	71 participants
Sex: Female, Male Female	36 Participants	72 Participants	36 Participants
Sex: Female, Male Male	35 Participants	70 Participants	35 Participants
Weight	61.6 kg STANDARD_DEVIATION 8.49	60.8 kg STANDARD_DEVIATION 7.98	60 kg STANDARD_DEVIATION 7.42

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 136	0 / 135
other Total, other adverse events	39 / 136	39 / 135
serious Total, serious adverse events	0 / 136	0 / 135

Outcome results

Primary

Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC

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: Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.

Population: 5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC	6638.12 x10^3 cells*h/uL	Standard Deviation 1404.376
US Neulasta Treatment	Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC	6554.04 x10^3 cells*h/uL	Standard Deviation 1465.072

Primary

Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC

Maximum measured absolute neutrophil count (ANC).

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC	38.82 x10^3 cells/uL	Standard Deviation 9.009
US Neulasta Treatment	Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC	37.97 x10^3 cells/uL	Standard Deviation 9.258

Primary

Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]

Area under the serum concentration versus time curve from time zero to infinity. Where AUC\[0-infinity\]= AUC\[0-t\] + Ct/λz(lambda-z), Ct is the last measurable concentration and λz(lambda-z) is the terminal rate constant.

Time frame: Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.

Population: 3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]	21015.8632 ng.h/mL	Standard Deviation 12985.376
US Neulasta Treatment	Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]	18327.4192 ng.h/mL	Standard Deviation 11156.158

Primary

Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]

Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]	474.269 ng/mL	Standard Deviation 240.2247
US Neulasta Treatment	Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]	425.578 ng/mL	Standard Deviation 219.8054

Secondary

PD Endpoint: AUEC[0-t], Baseline-adjusted ANC

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

Population: 5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PD Endpoint: AUEC[0-t], Baseline-adjusted ANC	4626.40 x10^3cells*h/uL	Standard Deviation 1163.806
US Neulasta Treatment	PD Endpoint: AUEC[0-t], Baseline-adjusted ANC	4565.80 x10^3cells*h/uL	Standard Deviation 1278.987

Secondary

PD Endpoint: E[Max], Baseline-adjusted ANC

Maximum measured absolute neutrophil count (ANC)

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PD Endpoint: E[Max], Baseline-adjusted ANC	34.66 x10^3 cells/uL	Standard Deviation 8.531
US Neulasta Treatment	PD Endpoint: E[Max], Baseline-adjusted ANC	33.84 x10^3 cells/uL	Standard Deviation 8.863

Secondary

PD Endpoint: t[1/2] for Baseline-adjusted ANC

The terminal half-life will be calculated as 0.693/λz(lamda-z).

Population: 5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PD Endpoint: t[1/2] for Baseline-adjusted ANC	55.98 h	Standard Deviation 34.973
US Neulasta Treatment	PD Endpoint: t[1/2] for Baseline-adjusted ANC	56.27 h	Standard Deviation 31.671

Secondary

PD Endpoint: T[Max], Baseline-adjusted ANC

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

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PD Endpoint: T[Max], Baseline-adjusted ANC	67.231 h	Standard Deviation 16.0553
US Neulasta Treatment	PD Endpoint: T[Max], Baseline-adjusted ANC	63.734 h	Standard Deviation 20.7

Secondary

PD Endpoint: T[Max] for Baseline Non-adjusted ANC

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

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PD Endpoint: T[Max] for Baseline Non-adjusted ANC	67.231 h	Standard Deviation 16.0553
US Neulasta Treatment	PD Endpoint: T[Max] for Baseline Non-adjusted ANC	63.734 h	Standard Deviation 13.1649

Secondary

PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC

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

Population: 5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC	0.02 1/h	Standard Deviation 0.011
US Neulasta Treatment	PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC	0.02 1/h	Standard Deviation 0.013

Secondary

PK Endpoint: Pegfilgrastim AUC[0-t]

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.

Population: 3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PK Endpoint: Pegfilgrastim AUC[0-t]	21001.567 ng.h/mL	Standard Deviation 12983.9811
US Neulasta Treatment	PK Endpoint: Pegfilgrastim AUC[0-t]	18312.112 ng.h/mL	Standard Deviation 11156.5248

Secondary

PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]

The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\]0-t\])/AUC0-infinity\] x 100.

Population: 3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]	0.105 percent of AUC	Standard Deviation 0.117
US Neulasta Treatment	PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]	0.139 percent of AUC	Standard Deviation 0.1726

Secondary

PK Endpoint: Pegfilgrastim R^2 Adjusted

Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz. R\^2 is the coefficient of Determination and can range from 0 to 1,; with higher values indicating greater predictability.

Population: 3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PK Endpoint: Pegfilgrastim R^2 Adjusted	0.968 Coefficient of Determination	Standard Deviation 0.0543
US Neulasta Treatment	PK Endpoint: Pegfilgrastim R^2 Adjusted	0.967 Coefficient of Determination	Standard Deviation 0.0344

Secondary

PK Endpoint: Pegfilgrastim t[1/2]

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

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PK Endpoint: Pegfilgrastim t[1/2]	39.963 h	Standard Deviation 18.5548
US Neulasta Treatment	PK Endpoint: Pegfilgrastim t[1/2]	44.824 h	Standard Deviation 29.3461

Secondary

PK Endpoint: Pegfilgrastim T[Max]

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

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PK Endpoint: Pegfilgrastim T[Max]	26.189 h	Standard Deviation 6.811
US Neulasta Treatment	PK Endpoint: Pegfilgrastim T[Max]	25.754 h	Standard Deviation 7.6188

Secondary

PK Endpoint: Pegfilgrastim λz(Lambda-z)

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.

Population: 3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Arm	Measure	Value (MEAN)	Dispersion
INTP5 Treatment	PK Endpoint: Pegfilgrastim λz(Lambda-z)	0.021 1/h	Standard Deviation 0.0094
US Neulasta Treatment	PK Endpoint: Pegfilgrastim λz(Lambda-z)	0.019 1/h	Standard Deviation 0.0088

Other Pre-specified

Immunogenicity: Presence of Anti-drug Antibodies

Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. 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. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. 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: 0-71 Days

Population: Only a fraction of the population was tested for Immunogenicity. Only participants that displayed treatment related AEs with plausible immune-mediated pathology were analysed for immunogenicity. The data below represents the outcomes for the fraction of each arm that was tested.

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Negative for anti-drug-	3 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Positive for anti-PegG-CSF	1 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Not Tested for Immunogenicity	60 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Neutralizing antibody	0 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Negative for anti-drug-	0 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Positive for anti-PegG-CSF	0 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Not Tested for Immunogenicity	64 Participants
INTP5 Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Neutralizing antibody	0 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Neutralizing antibody	0 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Negative for anti-drug-	2 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Negative for anti-drug-	0 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Positive for anti-PegG-CSF	1 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Not Tested for Immunogenicity	65 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Not Tested for Immunogenicity	62 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period II	Positive for anti-PegG-CSF	0 Participants
US Neulasta Treatment	Immunogenicity: Presence of Anti-drug Antibodies	Period I	Neutralizing antibody	0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Comparative, Pharmacokinetic and Pharmacodynamic Study of Subcutaneous Injections of INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects.

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Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC

Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC

Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]

Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]

PD Endpoint: AUEC[0-t], Baseline-adjusted ANC

PD Endpoint: E[Max], Baseline-adjusted ANC

PD Endpoint: t[1/2] for Baseline-adjusted ANC

PD Endpoint: T[Max], Baseline-adjusted ANC

PD Endpoint: T[Max] for Baseline Non-adjusted ANC

PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC

PK Endpoint: Pegfilgrastim AUC[0-t]

PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]

PK Endpoint: Pegfilgrastim R^2 Adjusted

PK Endpoint: Pegfilgrastim t[1/2]

PK Endpoint: Pegfilgrastim T[Max]

PK Endpoint: Pegfilgrastim λz(Lambda-z)

Immunogenicity: Presence of Anti-drug Antibodies