CTRI/2023/01/049031已完成1 期
A Single Dose, Double-Blind, Two-Period, Two Sequence, Crossover Comparative Pharmacokinetic Study of DRL_DA, and EU approved Reference Medicinal Product (Aranesp®), Administered by the Intravenous Route to Male Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Pharmacokinetic parameters (calculated by standard non-compartmental
研究概览
简要总结
It is a Phase 1 comparative study conducted by Dr. Reddy’s Laboratories Ltd in male volunteers with DRL_DA vs. Aranesp to compare the Pharmacokinetic parameters.
Dr.Reddy’s darbepoetin alfa (company product code: DRL_DA) is being developed as a biosimilar to the Reference Medicinal Product (RMP-EU approved Aranesp®) as a part of global development program. Normal healthy volunteers (NHV) are the population of choice (unless precluded for safety reasons) to establish PK similarity. The current study will be performed only in male subjects to avert gender-related variability. The 60 mcg IV single dose is known to be safe for administration to NHV as it has been tested with appropriate safety and tolerability in prior studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 50.00 Year(s)（—）
- 性别
- Male
入选标准
- •Healthy Male volunteers, 18 to 50 years of age (both age inclusive) at the time of signing informed consent.
- •Body mass index between 18.
- •30.0 kg/ m2 (both inclusive) and body weight of 55.0 – 95.0 kg (both inclusive).
- •In general good health as determined by a qualified physician based on a comprehensive medical history, physical examination including vital signs, laboratory hematology, clinical chemistry, urinalysis, and 12-lead electrocardiogram (ECG) before randomization.
- •Screening parameters (vital signs, physical examination, clinical laboratory tests, 12-lead ECG, thyroid function and coagulation parameters) within the normal range or outside the normal range but assessed as clinically non-significant by the Investigator (unless the value constitutes an explicit exclusion criterion).
- •Subjects or their female partner (if they are WOCBP) must be willing to use at least one highly effective method of contraception as described below from the time of first Investigational Medicinal Product (IMP) administration until 3 months after last dosing (Second period dosing). Highly effective birth control measures per CTFG (Clinical Trials Facilitation and Coordination Group) guidelines 2014 include the following: For Subject: 5.1 Permanently sterile by bilateral orchidectomy 5.2 Sexual abstinence For female partner of male Subject 5.3 Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation.
- •oral, intravaginal, and transdermal; 5.4 Progestogen-only hormonal contraception associated with inhibition of ovulation.
- •oral, injectable, implantable; 5.5 Intrauterine device; 5.6 Intrauterine hormone-releasing system; 5.7 Bilateral tubal occlusion; 5.8 Vasectomized partner; 5.9 Sexual abstinence
- •Capable, and amenable to providing written informed consent to the study requirements.
- •Willing to stay on study restrictions for 16 weeks and abide by the study processes during the follow up period if and as applicable.
排除标准
- •Positive test result for syphilis, hepatitis B, hepatitis C, or HIV-1 or -
- •Any prior exposure to darbepoetin or to any other erythropoiesis stimulating agent including investigational products [example: Epogen® (epoetin alfa) and its biosimilar/s].
- •Allergy or hypersensitivity to any recombinant human or humanized antibodies, other therapeutic proteins, or any excipients in the study formulations as well as latex allergy.
- •Hemoglobin concentration higher than “ULN.
- •0.5 gm/dlâ€; reticulocyte percent >3% serum ferritin <100 mcg/L or transferrin saturation NOT within the normal laboratory reference range for the study site or transferrin or serum vitamin B12 or folate below the lower limit of the reference range at Screening. Note: “ULN – 0.5 gm/dlâ€: Upper Limit of Normal reference range of the study site for haemoglobin subtracted with 0.5 gm/dl
- •Known history or presence of hemoglobinopathies including but not limited to sickle cell disease or trait and thalassemias. If suspecting any, to be ruled out by appropriate tests.
- •History and/ or current presence of clinically significant (in the opinion of the Investigator) atopic allergy (e.g., asthma including childhood asthma, urticaria, angioedema, eczematous dermatitis), hypersensitivity or allergic reactions or any history or presence of vasculitis or psoriasis.
- •Blood donation, participation in any study requiring repeated blood sampling or hemorrhage requiring treatment or any transfusion in the past 3 months.
- •Screening or baseline blood pressure higher than 140 mm Hg (systolic) or higher than 90 mm Hg (diastolic) or volunteers currently on anti-hypertensive drugs. Note: Up to two repeats in different days are allowed (repeats on the same visit can be done if white coat hypertension is suspected) and, in this case, the mean of the measurements will be used to decide on eligibility. Blood pressure is to be measured in the sitting position after 5 minutes rest on the same position.
- •History of relevant (in the Opinion of the Investigator) orthostatic hypotension, fainting spells, or blackouts as well as history of difficulties with blood sampling which potentially may interfere with the study objectives, as per the opinion of the Investigator.
- •QTc (Fridericia correction) longer than 450 milliseconds or other ECG abnormalities such as atrial fibrillation, atrial flutter, Wolf-Parkinson-White syndrome, or presence of a cardiac pacemaker or any other ECG abnormality considered clinically relevant by the Investigator.
- •History or presence of any clinically relevant nervous system disease including, but not restricted to any stroke/TIA or of seizures other than febrile seizures before the age of 5 years.
- •History of and/or current gastrointestinal, neurological, renal, endocrine, pulmonary, hepatic, cardiovascular (including history of or presence of angina, exertional dyspnea, orthopnea, congestive heart failure or myocardial infarction and thrombotic or embolic episode requiring treatment), hematological [including pancytopenia, aplastic anemia, or blood dyscrasia and coagulopathies or an International Normalized Ratio (INR) higher than 1.5] or metabolic (including known diabetes mellitus) disease. This criterion also includes any disorder or condition that, in the Investigator’s opinion, may interfere with the safety of the subject, the study evaluations or the subject compliance to the study procedures and limitations.
- •Participants who have abnormal liver function tests as evaluated by the investigator will be excluded from the study. A single repeat in a different day is allowed. Subjects who have documented evidence of presence of Gilbert’s disease may be included in the study if they have total bilirubin of <3 mg/dL with indirect bilirubin contributing to >80% of the total bilirubin as per the laboratory test.
- •Participation in an interventional or Phase 1 study in the last three months, currently is on follow-up visit schedule for any study, participation in more than 3 studies of experimental drug products in the past 12 months, or intake of an investigational drug in another trial within 3 months or 5 half-lives (whichever is longer) prior to intake of IMP in this trial or planned intake of an investigational drug during the course of this trial. Some examples of drugs, that are exceptions to this criterion and their adequate washout period (either as an investigational product or for treatment) are provided for reference: 14.1 Medications which require longer washout: 14.1.1 10 weeks: Bismuth salts, digitoxin, fluoxetine, flurazepam, medazepam, mephenytoin, mephobarbital, phenprocoumone, phenylbutazone, pimozide, pirimethamine, phenobarbital, primidone, protryptiline, teicoplanin 14.1.2 18 weeks: flunarizine, mefloquine, trimethadione 14.1.3 26 weeks: gold salts, immunoglobulins (antitetanus and antirabies post-exposure prophylaxis allowed until 3 weeks predose) or antibodies (monoclonal or not) systemic retinoids, chloroquine, hydroxychloroquine, and amiodarone
- •History of any cancer, lymphoma, or leukemia other than non-melanoma skin cancer completely excised at least 5 years before study entry.
- •Major surgery within the past 6 months, or any surgery planned within 3 months of study enrolment.
- •Current smokers or those who gave up smoking less than 3 months prior to screening, (thus 3 months cessation required at screening time), tobacco chewer or positive in the urine cotinine test at Screening and check-in/admission to clinical facility.
- •Positive test for alcohol in breath test or drugs of abuse (benzodiazepine, amphetamines, barbiturates, cocaine, methadone, phencyclidine, 3, 4 methylenedioxymethamphetamine (ecstasy), tetrahydrocannabinol, and opiates) in urine at Screening or on the day before dosing.
- •Participation in professional sports or planned participation in an official sports competition during the study period.
结局指标
主要结局
Pharmacokinetic parameters (calculated by standard non-compartmental
时间窗: period 2 day 42 of study
methods on actual sampling times): AUC0-t and AUC0-∞
时间窗: period 2 day 42 of study
次要结局
- •Pharmacokinetic parameters: Cmax, tmax, apparent terminal decline rate constant λz (also known as apparent terminal elimination rate constant kel), t1/2, CL and Vss; %AUCext will be reported to evaluate the coverage of AUC by the sampling schedule but is not considered a pharmacokinetic endpoint.(•Pharmacodynamic parameters: Emax and AUEC of reticulocyte count and percentage)
研究者
研究点 (1)
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