Trial Outcomes & Findings for 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. (NCT NCT04014062)
NCT ID: NCT04014062
Last Updated: 2019-10-04
Results Overview
Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
144 participants
Primary outcome timeframe
Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8),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.
Results posted on
2019-10-04
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Period I: Dosing
STARTED
|
71
|
71
|
|
Period I: Dosing
COMPLETED
|
64
|
65
|
|
Period I: Dosing
NOT COMPLETED
|
7
|
6
|
|
Period II: Crossover Dosing
STARTED
|
64
|
65
|
|
Period II: Crossover Dosing
COMPLETED
|
64
|
65
|
|
Period II: Crossover Dosing
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Period I: Dosing
Medical Grounds
|
4
|
5
|
|
Period I: Dosing
Withdrawal by Subject
|
3
|
1
|
Baseline Characteristics
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.
Baseline characteristics by cohort
| Measure |
INTP5 Period I, US Neulasta Period II Crossover
n=71 Participants
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.
|
US Neulasta Period I, INTP5 Period II Crossover
n=71 Participants
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.
|
Total
n=142 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
India
|
71 participants
n=5 Participants
|
71 participants
n=7 Participants
|
142 participants
n=5 Participants
|
|
Height
|
159.1 cm
STANDARD_DEVIATION 7.99 • n=5 Participants
|
159.3 cm
STANDARD_DEVIATION 9.00 • n=7 Participants
|
159.2 cm
STANDARD_DEVIATION 8.48 • n=5 Participants
|
|
Weight
|
60 kg
STANDARD_DEVIATION 7.42 • n=5 Participants
|
61.6 kg
STANDARD_DEVIATION 8.49 • n=7 Participants
|
60.8 kg
STANDARD_DEVIATION 7.98 • n=5 Participants
|
|
BMI
|
23.77 kg/m^2
STANDARD_DEVIATION 2.788 • n=5 Participants
|
24.32 kg/m^2
STANDARD_DEVIATION 3.188 • n=7 Participants
|
24.04 kg/m^2
STANDARD_DEVIATION 2.996 • n=5 Participants
|
|
Age, Continuous
|
34.7 years
STANDARD_DEVIATION 5.74 • n=5 Participants
|
32.5 years
STANDARD_DEVIATION 6.38 • n=7 Participants
|
33.6 years
STANDARD_DEVIATION 6.15 • n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
71 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]
|
474.269 ng/mL
Standard Deviation 240.2247
|
425.578 ng/mL
Standard Deviation 219.8054
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=127 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]
|
21015.8632 ng.h/mL
Standard Deviation 12985.3760
|
18327.4192 ng.h/mL
Standard Deviation 11156.1580
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC
|
38.82 x10^3 cells/uL
Standard Deviation 9.009
|
37.97 x10^3 cells/uL
Standard Deviation 9.258
|
PRIMARY outcome
Timeframe: 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.
Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=125 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC
|
6638.12 x10^3 cells*h/uL
Standard Deviation 1404.376
|
6554.04 x10^3 cells*h/uL
Standard Deviation 1465.072
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=127 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PK Endpoint: Pegfilgrastim AUC[0-t]
|
21001.567 ng.h/mL
Standard Deviation 12983.9811
|
18312.112 ng.h/mL
Standard Deviation 11156.5248
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PK Endpoint: Pegfilgrastim T[Max]
|
26.189 h
Standard Deviation 6.8110
|
25.754 h
Standard Deviation 7.6188
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=127 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PK Endpoint: Pegfilgrastim λz(Lambda-z)
|
0.021 1/h
Standard Deviation 0.0094
|
0.019 1/h
Standard Deviation 0.0088
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=127 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PK Endpoint: Pegfilgrastim R^2 Adjusted
|
0.968 Coefficient of Determination
Standard Deviation 0.0543
|
0.967 Coefficient of Determination
Standard Deviation 0.0344
|
SECONDARY outcome
Timeframe: 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).
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PK Endpoint: Pegfilgrastim t[1/2]
|
39.963 h
Standard Deviation 18.5548
|
44.824 h
Standard Deviation 29.3461
|
SECONDARY outcome
Timeframe: 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
The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\]0-t\])/AUC0-infinity\] x 100.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=127 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]
|
0.105 percent of AUC
Standard Deviation 0.117
|
0.139 percent of AUC
Standard Deviation 0.1726
|
SECONDARY outcome
Timeframe: 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)
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PD Endpoint: T[Max] for Baseline Non-adjusted ANC
|
67.231 h
Standard Deviation 16.0553
|
63.734 h
Standard Deviation 13.1649
|
SECONDARY outcome
Timeframe: 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)
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PD Endpoint: E[Max], Baseline-adjusted ANC
|
34.66 x10^3 cells/uL
Standard Deviation 8.531
|
33.84 x10^3 cells/uL
Standard Deviation 8.863
|
SECONDARY outcome
Timeframe: 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.
Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=125 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PD Endpoint: AUEC[0-t], Baseline-adjusted ANC
|
4626.40 x10^3cells*h/uL
Standard Deviation 1163.806
|
4565.80 x10^3cells*h/uL
Standard Deviation 1278.987
|
SECONDARY outcome
Timeframe: 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)
Outcome measures
| Measure |
INTP5 Treatment
n=129 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=129 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PD Endpoint: T[Max], Baseline-adjusted ANC
|
67.231 h
Standard Deviation 16.0553
|
63.734 h
Standard Deviation 20.7
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=125 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC
|
0.02 1/h
Standard Deviation 0.011
|
0.02 1/h
Standard Deviation 0.013
|
SECONDARY outcome
Timeframe: 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.
The terminal half-life will be calculated as 0.693/λz(lamda-z).
Outcome measures
| Measure |
INTP5 Treatment
n=128 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=125 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
PD Endpoint: t[1/2] for Baseline-adjusted ANC
|
55.98 h
Standard Deviation 34.973
|
56.27 h
Standard Deviation 31.671
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0-71 DaysPopulation: 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.
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.
Outcome measures
| Measure |
INTP5 Treatment
n=64 Participants
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
|
US Neulasta Treatment
n=65 Participants
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
|
|---|---|---|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period I · Negative for anti-drug-
|
3 Participants
|
2 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period I · Positive for anti-PegG-CSF
|
1 Participants
|
1 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period I · Not Tested for Immunogenicity
|
60 Participants
|
62 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period I · Neutralizing antibody
|
0 Participants
|
0 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period II · Negative for anti-drug-
|
0 Participants
|
0 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period II · Positive for anti-PegG-CSF
|
0 Participants
|
0 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period II · Not Tested for Immunogenicity
|
64 Participants
|
65 Participants
|
|
Immunogenicity: Presence of Anti-drug Antibodies
Period II · Neutralizing antibody
|
0 Participants
|
0 Participants
|
Adverse Events
INTP5 Treatment
Serious events: 0 serious events
Other events: 39 other events
Deaths: 0 deaths
US Neulasta Treatment
Serious events: 0 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
INTP5 Treatment
n=136 participants at risk
INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
Given that this was a crossover design, AE totals for the entire study are reported comprehensively for Period I (71 Subjects) and Period II (65 Subjects) combined for the 136 subjects who received this treatment. Due to participant dropout between treatments, the number at risk for a given treatment is lower than the starting population for the study.
|
US Neulasta Treatment
n=135 participants at risk
US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.
Given that this was a crossover design, AE totals for the entire study are reported comprehensively for Period I (71 Subjects) and Period II (64 Subjects) combined for the 135 subjects who received this treatment. Due to participant dropout between treatments, the number at risk for a given treatment is lower than the starting population for the study.
|
|---|---|---|
|
Eye disorders
Lacrimation increased
|
0.00%
0/136 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/136 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/136 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Gastrointestinal disorders
Hyperchlorhydria
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Gastrointestinal disorders
Toothache
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
4/136 • Number of events 4 • 79 days
|
1.5%
2/135 • Number of events 2 • 79 days
|
|
General disorders
Injection site pain
|
1.5%
2/136 • Number of events 2 • 79 days
|
3.7%
5/135 • Number of events 5 • 79 days
|
|
General disorders
Pyrexia
|
0.74%
1/136 • Number of events 1 • 79 days
|
2.2%
3/135 • Number of events 3 • 79 days
|
|
Injury, poisoning and procedural complications
Injury
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
|
Investigations
Blood creatinine increased
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
|
Investigations
Haemoglobin decreased
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
|
Investigations
Human chorionic gonadotropin increased
|
1.5%
2/136 • Number of events 2 • 79 days
|
2.2%
3/135 • Number of events 3 • 79 days
|
|
Investigations
Platelet count decreased
|
0.00%
0/136 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Investigations
Protein urine present
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
|
Investigations
Red blood cells urine
|
0.00%
0/136 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Investigations
Red blood cells urine positive
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.8%
16/136 • Number of events 17 • 79 days
|
14.1%
19/135 • Number of events 19 • 79 days
|
|
Nervous system disorders
Headache
|
8.8%
12/136 • Number of events 12 • 79 days
|
8.9%
12/135 • Number of events 12 • 79 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/136 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.5%
2/136 • Number of events 2 • 79 days
|
0.74%
1/135 • Number of events 1 • 79 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.74%
1/136 • Number of events 1 • 79 days
|
0.00%
0/135 • 79 days
|
Additional Information
Dr. Anshul Attrey, M.D. Principal Investigator
Lambda Therapeutic Research Ltd.
Phone: +91-79-40202020
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place