Clinical trial NCT04014062: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetic Bioequivalence Study in Human Healthy Volunteers
Keywords: Pegfilgrastim
Biosimilar
Bioequivalence
Pharmacokinetics
Pharmacodynamics
Safety
Healthy Volunteers
Lead sponsor: Intas Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Lambda Therapeutic Research Ltd.
First posted: 2019-07-10
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]
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.
measure: Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]
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.
measure: Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC
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.
measure: Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC
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.
Secondary outcomes:
measure: PK Endpoint: Pegfilgrastim AUC[0-t]
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.
measure: PK Endpoint: Pegfilgrastim T[Max]
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.
measure: PK Endpoint: Pegfilgrastim λz(Lambda-z)
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.
measure: PK Endpoint: Pegfilgrastim R^2 Adjusted
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.
measure: PK Endpoint: Pegfilgrastim t[1/2]
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.
measure: PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]
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.
measure: PD Endpoint: T[Max] for Baseline Non-adjusted ANC
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.
measure: PD Endpoint: E[Max], Baseline-adjusted ANC
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.
measure: PD Endpoint: AUEC[0-t], Baseline-adjusted ANC
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.
measure: PD Endpoint: T[Max], Baseline-adjusted ANC
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.
measure: PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC
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.
measure: PD Endpoint: t[1/2] for Baseline-adjusted ANC
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.
Other outcomes:
measure: Immunogenicity: Presence of Anti-drug Antibodies
timeFrame: 0-71 Days
Locations:
city: Ahmedabad
country: India
facility: Lambda Therapeutic Research Ltd.
state: Gota
Study officials:
affiliation: Lambda Therapeutic Research Ltd.
name: Anshul Attrey, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Intas Pharmaceuticals, Ltd.
name: Vinu Jose, M.D.
role: STUDY_DIRECTOR
References: