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.

NCT04014062 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 0553-17
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetic Bioequivalence Study in Human Healthy Volunteers

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]

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

  Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8),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.

• 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.

  Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8),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.

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

  Maximum measured absolute neutrophil count (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  Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13),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.

• 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.

  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 (12)

• 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.

• 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.

• 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.

• 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.

• 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.

Other Outcomes (1)

• Immunogenicity: Presence of Anti-drug Antibodies

  0-71 Days

Study Arms (2)

INTP5 Period I Crossover

EXPERIMENTAL

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.

Combination Product: INTP5; Combination Product: US Neulasta

US Neulasta Period I Crossover

ACTIVE COMPARATOR

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.

Combination Product: INTP5; Combination Product: US Neulasta

Interventions

INTP5 COMBINATION_PRODUCT

INTP5: A proposed pegfilgrastim biosimilar to US Neulasta.

INTP5 Period I Crossover; US Neulasta Period I Crossover

US Neulasta COMBINATION_PRODUCT

US Neulasta: FDA-approved pegfilgrastim innovator product.

INTP5 Period I Crossover; US Neulasta Period I Crossover

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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.
• Volunteer who is a Non-smoker
• Able to understand and comply with the study procedures, in the opinion of the investigator.
• Able to give voluntary written informed consent for participation in the trial.
• 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.

You may not qualify if:

• 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.
• 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.
• Known case of hereditary fructose intolerance.
• Subjects with latex allergies will be excluded as the needle cover on the single-use pre-filled syringe contains dry natural rubber (latex).
• Any clinically significant laboratory finding including ANC, platelet, RBC count or hemoglobin level at the time of screening.
• 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.
• Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or NSAIDs induced urticaria.
• Subjects with a history of pulmonary infiltrate or pneumonia in the last 6 months.
• History of any hematologic disease including sickle cell disorders.
• Smokers, or who have smoked within last six months prior to start of the study.
• Ingestion or use of any prescribed medication at any time within 1 month prior to receiving first dose in Period-I.
• 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).
• 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.
• Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.
• Positive result for human immunodeficiency virus (HIV I \&/or II) and/or hepatitis B and C tests.

Sponsors & Collaborators

• Intas Pharmaceuticals, Ltd.: lead
• Lambda Therapeutic Research Ltd.: collaborator

Study Sites (1)

Lambda Therapeutic Research Ltd.

Ahmedabad, Gota, Ahmedabad-382481, India

Location

Results Point of Contact

• Title: Dr. Anshul Attrey, M.D. Principal Investigator
• Organization: Lambda Therapeutic Research Ltd.

anshulattrey@lambda-cro.com

+91-79-40202020

Study Officials

• Anshul Attrey, M.D.

  Lambda Therapeutic Research Ltd.

  PRINCIPAL INVESTIGATOR

• Vinu Jose, M.D.

  Intas Pharmaceuticals, Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 10, 2019
• Study Start: February 12, 2018
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: October 4, 2019
• Results First Posted: October 4, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)