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.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 2
- 主要终点
- Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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^
- •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.
排除标准
- •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.
- •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.
- •Positive result for human immunodeficiency virus (HIV I &/or II) and/or hepatitis B and C tests.
- •History or presence of cancer because of which anticipated life span is less than 5 years as per the investigator's assessment.
- •History or presence of psychiatric disorders.
- •Presence of tattoo or scars or any type of skin lesions due to infection, burning, wound or inflammation at the proposed site of injection.
- •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.
- •Consumption of grape fruit or grape fruit products within 72 hours prior to receiving study drug in Period-I.
- •A history of difficulty in donating blood.
- •Females, pregnant or lactating, or planning to become pregnant during the course of the study or found positive in pregnancy test at screening.
- •Any infections in the last 4 weeks before receiving study medication in Period-I.
研究组 & 干预措施
INTP5 Period I 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.
干预措施: US Neulasta (Combination Product)
US Neulasta Period I 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.
干预措施: US Neulasta (Combination Product)
INTP5 Period I 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.
干预措施: INTP5 (Combination Product)
US Neulasta Period I 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.
干预措施: INTP5 (Combination Product)
结局指标
主要结局
Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]
时间窗: 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.
Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC
时间窗: 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).
Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]
时间窗: 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: AUEC[0-t] for Baseline Non-adjusted ANC
时间窗: 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.
次要结局
- 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 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)