Open-label Randomized Crossover Two Period Single Dose Bioequivalence Study of Two Formulations Aceclofenac Tablets 100 mg (Pharmtechnology LLC, Republic of Belarus) and Airtal® Tablets 100 mg (Gedeon Richter- RUS", Russia / Gedeon Richter, Hungary; MA Holder: Almiral S.A., Spain) in Healthy Volunteers Under Fasting Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- AUC0-t of aceclofenac in plasma after administration of the test and the reference.
研究概览
简要总结
This is an open-label, randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Airtal ®, 100 mg film-coated tablets) or the test (Aceclofenac, 100 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.
详细描述
This is an open-labeled, randomized, two period, crossover, a single-center, comparative, single-dose study, in which 36 healthy adult subjects will receive one of the study treatments during each study period.
The objective of this study is to determine the bioequivalence of two different formulations of aceclofenac after a single oral dose administration under fasting conditions.
Subject eligibility for this study will be determined at the screening visit and eligible subjects will be admitted to the clinical research unit at least 12 hours prior to drug administration for each study period.
Hospitalization in the first period of the study will last no more than 37 hours, after which, in the absence of indications for an extension of hospitalization, each subject will be released home; after that, the first period of the study will be completed.
The procedures of the second study period will be identical to the first period.
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 european men or women aged between 18 to 45 years
- •The written consent of the volunteer to be included in the study
- •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 according to Quetelet's weight-height index
- •For female:
- •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;
- •negative pregnancy test;
- •adherence to reliable methods of contraception for female of childbearing potential: sexual continence, or condom + spermicide, or diaphragm + spermicide, started at least 14 days before the first dose of the study drug; intrauterine contraception is also a reliable method of contraception, installed at least 4 weeks before taking the study drugs in the first period;
- •сonsent to use these methods of contraception within 30 days after taking the drug in the second period;
- •women who do not use acceptable methods of contraception, if they are considered incapable of childbearing, will also be able to 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 pathologies that may cause the cessation of menstruation);
- •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;
- •For male: consent to use a double barrier method of contraception (condom + spermicide) or complete sexual abstinence, as well as consent not to participate in sperm donation during the entire study and 30 days after taking the drug in the second period.
- •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.
排除标准
- •burdened allergic history, hypersensitivity to any ACE inhibitors, including aceclofenac or excipients that are part of any of the investigational drugs, or intolerance to these components;
- •bronchospasm, urticaria, rhinitis after taking acetylsalicylic acid or other NSAIDs in history (complete or incomplete acetylsalicylic acid intolerance syndrome - rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma);
- •bleeding or perforation of the gastrointestinal tract associated with the use of NSAIDs in history;
- •acute bleeding or diseases accompanied by bleeding in the last 2 months;
- •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;
- •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 ≥ 139 mm Hg and / or diastolic blood pressure (DBP) ≤ 70 mm Hg or ≥ 89 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;
- •the use of injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems and other hormonal contraceptives for 60 days before taking the drug in the first period;
- •use of any drugs including herbs and food additives, vitamins that can have a significant effect on the PK of lisinopril or data on the effect of which on the pharmacokinetics of lisinopril 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;
- •taking known inhibitors or inducers of microsomal liver enzymes (barbiturates, omeprazole, cimetidine, etc.) or antiviral drugs less than 2 months before taking the drug in the first study period;
- •donation of plasma or blood (450 ml or more) less than 2 months before taking the drug in the first period;
- •adherence to any low-sodium diet within 2 weeks prior to taking the drug in the first study period, or adherence to a special diet (vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical exercise);
- •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 500 ml of beer, 200 ml of dry wine or 50 ml of spirits ethyl 40%) or history of alcoholism, drug addiction, drug abuse;
- •inability to refrain from intensive physical activity and contact sports less than 24 hours before taking the drug in the first period;
- •smoking more than 10 cigarettes per day less than 24 hours before taking the drug in the first 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;
- •mental, physical and other reasons that do not allow the subject to adequately assess their behavior and correctly fulfill the conditions of the Research Protocol;
- •tattooing and piercing within 30 days prior to first drug administration;
- •difficulty swallowing tablets;
- •difficulty with taking blood;
研究组 & 干预措施
Sequence TR
18 subjects assigned to the sequence TR will receive a single 100 mg dose of the test product Aceclofenac (1 x 100 mg tablet), marked as T in the sequence, in Period 1 and a single 100 mg dose of the reference product Airtal ® (1 x 100 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: Aceclofenac film-coated tablet 100 mg (Drug)
Sequence TR
18 subjects assigned to the sequence TR will receive a single 100 mg dose of the test product Aceclofenac (1 x 100 mg tablet), marked as T in the sequence, in Period 1 and a single 100 mg dose of the reference product Airtal ® (1 x 100 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: Airtal® film-coated tablet 100 mg (Drug)
Sequence RT
18 subjects assigned to the sequence RT will receive a single 100 mg dose of the test product Airtal ® (1 x 100 mg tablet), marked as R in the sequence, in Period 1 and a single 100 mg dose of thetest product Aceclofenac (1 x 100 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: Aceclofenac film-coated tablet 100 mg (Drug)
Sequence RT
18 subjects assigned to the sequence RT will receive a single 100 mg dose of the test product Airtal ® (1 x 100 mg tablet), marked as R in the sequence, in Period 1 and a single 100 mg dose of thetest product Aceclofenac (1 x 100 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: Airtal® film-coated tablet 100 mg (Drug)
结局指标
主要结局
AUC0-t of aceclofenac in plasma after administration of the test and the reference.
时间窗: Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration using the linear trapezoidal method.
Cmax of aceclofenac in plasma after administration of the test and the reference products.
时间窗: Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.
Maximum observed concentration in plasma.
次要结局
- Tmax of aceclofenac in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)
- TLQC of aceclofenac in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)
- AUC0-INF of aceclofenac in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)
- Residual area of aceclofenac in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)
- Time point where the log-linear elimination phase begins (TLIN) of aceclofenac in plasma after administration of the test and the reference. products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)
- λZ of aceclofenac in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)
- Terminal elimination half-life (Thalf) of aceclofenac in plasma after administration of the test and the reference products.(Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 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 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.)