Randomized Crossover Two Period Single Dose Bioequivalence Study of Two Formulations Etoricoxib Tablets 120 mg (Pharmtechnology LLC, Republic of Belarus) and Arcoxia® Tablets 120 mg (Merck Sharp & Dohme B.V., Netherlands) in Healthy Volunteers Under Fasting Conditions
试验速览
- 阶段
- 1 期
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Cmax of etoricoxib in plasma after administration of the test and the reference products.
研究概览
简要总结
This is an open-labeled, randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Arcoxia®, 120 mg film-coated tablets) or the test (Etoricoxib, 120 mg film-coated tablets) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent.
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)
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
- •Healthy caucasian men or women aged between 18 to 45 years
- •Verified diagnosis "healthy" according to the anamnesis data and the results of standard clinical, laboratory and instrumental examination methods, physical examination and anamnestic examination
- •The results of an X-ray or fluorographic examination of the chest organs within the normal range (the results of an examination carried out within 12 months before the start of the study may be provided)
- •Body mass index 18.5-30 kg/m²
- •For female subject:
- •the results of the examination of the mammary glands (palpation or mammography) within the normal range according to the data obtained within 12 months before the start of the study,
- •Non-breastfeeding women,
- •Non-pregnant women (negative pregnancy test),
- •If subject is a female and is of childbearing potential, she should be practicing an acceptable method of birth control for the duration of the study (the entire time from at least 14 days before taking the drug in the first period and within 14 days after taking the drug in the second period): sexual continence, or condom + spermicide, or diaphragm + spermicide. Intrauterine contraception is also a reliable method of contraception, installed at least 4 weeks before taking the study drugs in the first period,
- •women who are not using acceptable methods of contraception if they are considered incapable of childbearing can participate in the study: women who have undergone a hysterectomy or tubal ligation, women with a clinical diagnosis of infertility, and women who are in menopause (at least a year without menstruation in the absence of alternative medical conditions),
- •in case of using contraceptives (injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems), the latter should be canceled at least 60 days before taking the drug in the first period;
- •Consent to use a double barrier method of contraception (condom + spermicide) or sexual continence, as well as consent not to take part in sperm donation from the moment of taking the drug in the first period, during the entire study and within 14 days after taking the drug in the second period research
- •Subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations
- •Burdened allergic history, hypersensitivity to etoricoxib or excipients that are part of any of the investigational drugs, or intolerance to these components.
- •Complete or incomplete combination of bronchial asthma, acute rhinitis, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or intolerance to other NSAIDs (including a history).
- •Increased risk of complications from the gastrointestinal tract due to the use of NSAIDs, peptic ulcer and duodenal ulcer in the acute stage or active gastrointestinal bleeding (including a history).
- •Hereditary intolerance to lactose or galactose (for example, congenital lactase deficiency or glucose-galactose malabsorption).
- •Clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood.
- •Other diseases that, in the opinion of the researcher, may affect the absorption, distribution, metabolism or excretion of both drugs, or increase the risk of negative consequences for the volunteer.
- •The presence of mental disorders, including a history.
- •Surgical interventions on the gastrointestinal tract, with the exception of appendectomy.
- •Acute infectious diseases that ended less than 4 weeks before taking the drug in the first period.
- •Dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study, if vomiting or diarrhea wasn't a manifestation of an infectious disease.
- •Clinically significant abnormalities on the ECG, the level of systolic blood pressure (SBP) measured in the sitting position at the time of screening <100 mm Hg or ≥ 130 mm Hg and / or diastolic blood pressure (DBP) <60 mm Hg or ≥ 85 mm Hg.
- •Heart rate less than 60 beats/min or more than 90 beats/min at the time of screening, respiratory rate less than 12 or more than 18 per minute at the time of screening, body temperature below 36.0 ° C or above 37.0 ° C at the time of screening.
- •Use of any prescription and OTC drugs:
- •including herbs and food additives, vitamins that can have a significant effect on the PK of etoricoxib or data on the effect of which on the pharmacokinetics of etoricoxib are unknown, as well as question the characterization of the volunteer as healthy, less than 14 days before taking the drug in the first period;
- •including the use of drugs that are inducers or inhibitors of isoenzymes CYP3A4 (HIV protease inhibitors, antifungal drugs of the azole group, clarithromycin, erythromycin, phenytoin, carbamazepine, phenobarbital, St. John's wort preparations, etc.), less than 30 days before taking the drug in the first period;
- •the use of injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems for 60 days before taking the drug in the first period.
- •Donation of plasma or blood (450 ml or more) less than 2 months (60 days) before taking the drug in the first period.
- •Consumption of caffeine and xanthine-containing drinks and products (tea, coffee, chocolate, cola, etc.), products containing poppy seeds, less than 48 hours before taking the drug in the first period.
- •Consumption of alcohol and alcohol-containing foods and beverages less than 48 hours before taking the drug in the first period.
- •Use of citrus fruits (including grapefruit and grapefruit juice) and cranberries (including juices, fruit drinks, etc.) less than 7 days before taking the drug in the first period.
- •Intake of more than 10 units alcohol per week (1 unit of alcohol is equivalent to ½ liter of beer, 200 ml dry wine or 50 ml of spirits) or history of alcoholism, drug addiction, drug abuse.
- •Intense physical activity less than 24 hours before taking the drug in the first period.
- •Smoking more than 10 cigarettes per day, including less than 24 hours before taking the drug in each period and during each study period.
- •Participation in other clinical trials of drugs less than 3 months before taking the drug in the first period.
- •Test positive for syphilis, hepatitis B, hepatitis C or HIV at the time of screening.
- •Positive pregnancy test at screening.
- •Breastfeeding.
- •Positive test for alcohol in exhaled air at screening.
- •Positive urinalysis for the content of narcotic and potent substances during screening (opiates, morphine, barbiturates, benzodiazepines, cannabinoids/marijuana).
- •The value of standard laboratory and instrumental parameters that go beyond the reference values.
- •Lack of intention of volunteers to comply with the Protocol requirements throughout the course of the study and/or lack, in the opinion of the Investigator, of the volunteers' ability to understand and evaluate the information on this study as part of the informed consent form signing process, in particular regarding the expected risks and possible discomfort.
- •Tattooing and piercing within 30 days prior to first drug administration.
- •Difficulty swallowing tablets.
- •Difficulty with taking blood (for example, difficult access to the veins).
排除标准
- 未提供
研究组 & 干预措施
Sequence TR
17 subjects assigned to the sequence TR will receive a single 120 mg dose of the test product Etoricoxib (1 x 120 mg tablet), marked as T in the sequence, in Period 1 and a single 120 mg dose of the reference product Arcoxia® (1 x 120 mg tablet), marked as R in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.
干预措施: Etoricoxib film-coated tablet 120 mg (Drug)
Sequence TR
17 subjects assigned to the sequence TR will receive a single 120 mg dose of the test product Etoricoxib (1 x 120 mg tablet), marked as T in the sequence, in Period 1 and a single 120 mg dose of the reference product Arcoxia® (1 x 120 mg tablet), marked as R in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.
干预措施: Arcoxia® film-coated tablet 120 mg (Drug)
Sequence RT
17 subjects assigned to the sequence RT will receive a single 120 mg dose of the reference product Arcoxia® (1 x 120 mg tablet), marked as R in the sequence, in Period 1 and a single 120 mg dose of the test product Etoricoxib (1 x 120 mg tablet), marked as T in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.
干预措施: Etoricoxib film-coated tablet 120 mg (Drug)
Sequence RT
17 subjects assigned to the sequence RT will receive a single 120 mg dose of the reference product Arcoxia® (1 x 120 mg tablet), marked as R in the sequence, in Period 1 and a single 120 mg dose of the test product Etoricoxib (1 x 120 mg tablet), marked as T in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.
干预措施: Arcoxia® film-coated tablet 120 mg (Drug)
结局指标
主要结局
Cmax of etoricoxib in plasma after administration of the test and the reference products.
时间窗: Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.
Maximum observed concentration in plasma.
AUC0-t of etoricoxib in plasma after administration of the test and the reference.
时间窗: Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method
次要结局
- Tmax of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- λZ of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- TLQC of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- Residual area of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- Time point where the log-linear elimination phase begins (TLIN) of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- AUC0-INF of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- Terminal elimination half-life (Thalf) of etoricoxib in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)
- Number of treatment-emergent adverse events for the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00, 96.00 hours after each drug administration.)