Prospective, Single Dose, Randomized, Open Label, Comparative, Cross-study to Establish Bioequivalence Between the New Formulation and the Approved Formulation for Levothyroxine (Eutirox® From Merck, S. A. de C. V.) Given as 3 Tablets of 200 μg p.o. in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Maximum Serum Concentration in Pre Dose Corrected Data (Cmax[aj]) of Levothyroxine (T4)
研究概览
简要总结
The study investigated the bioequivalence between the new and the approved formulation for levothyroxine.
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who have provided their written consent prior to any study-related activity
- •Ethnic origin: Mexicans
- •Body mass index from 18 to 27 kilogram per meter square (kg/m^2)
- •Normal vital signs (includes heart rate between 50 and 100 beats per minute, respiratory rate between 12 and 20 per minute, systolic blood pressure between 80 and 129 milimeter of mercury (mmHg) , diastolic blood pressure between 50 and 80 mmHg and temperature between 36.0 degree celsius and 37.0 degree celsius. The measurement will be made according to the instructive BE-IT-005 Medición de signos vitales)
- •Normal electrocardiogram [ECG]. No abnormalities are allowed, even though they are not relevant (PR, QRS, QT, QTcF should be within normal range; no conduction abnormalities are allowed, etcetera (etc)
- •All values in blood and urine tests should be within the normal range or showing no clinically relevant deviation as judged by the Investigator
- •Participants with thyroid panel results within normal range (T3 and T4 total and free, as well as thyroid-stimulating hormone (TSH) should be within the normal range)
- •Non-smoker at least in the last 3 months
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participation in the clinical study within 90 days prior to the first dose of the study drug
- •History of hypersensitivity to the study drug or its excipients
- •History or current asthma or any severe allergy (which requires hospitalization or prolonged therapy), allergy or intolerance to any food that, in the opinion of the investigator, poses a safety risk (allergy to iodine)
- •History of cardiovascular, renal, liver, metabolic, gastrointestinal, neurological, endocrine, hematopoietic (any type of anemia) conditions, mental disorder or organic abnormalities that may affect the pharmacokinetic study of the study drug
- •Any medical or surgical condition, including findings in the medical history or clinical assessment prior to the study, that in the opinion of the investigator poses a risk or contraindication for the participants participation in the study and may affect the study objectives, conduct or analysis
- •History or presence of alcohol abuse (average daily intake not higher than 3 units or weekly intake not higher than 21 units; 1 unit is equivalent to 340 mililiter (mL) of beer, 115 mL of wine or 43 mL of prepared drinks), psychoactive substances or chronic use of drugs
- •Participants who have been exposed to agents knows by inducing or inhibiting the liver enzymatic systems or who have taken potentially toxic drugs within the last 30 days to the study start-up
- •Participants who take drugs affecting the metabolism of the thyroid hormone, such as: oral contraceptives, hormonal implants, parenteral hormones, steroids, anabolic drugs, androgens, etc., or any drug affecting the levothyroxine's bioavailability such as the proton pump inhibitors or multivitamins, nutritional supplements or herbal products that may affect the study, except for the occasional use of paracetamol
- •Participants who have been hospitalized for any reason within the 60 days prior to the study start-up or who have been severely ill within the last 30 days prior to the study start-up
- •Participants who have donated or lost 450 mL of blood within the last 60 days prior to the study start-up
- •Participants non- smokers, who have smoked tobacco, cigarettes or consumed coffee, snuff or drinks containing xanthines such as caffeine, (tea, cocoa, chocolate, matte, cola, etc.) theobromine, theophylline, among others, affecting the pharmacokinetics of the drug in assessment, drinking alcohol, or charcoal-grilled foods consumed within twenty-four hours prior to administration the dose of medication
- •Screening biosafety positive tests for the human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis Venereal Disease Research Laboratory (VDRL)
- •Positive result in the abuse drugs screening tests, such as: amphetamines, benzodiazepines, cocaine, methamphetamines, morphine and tetrahydrocannabinoids
- •Presence of alcohol in breath test
- •Women pregnancy positive tests (qualitative and quantitative) at the screening and inclusion in each period
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Reference Eutirox®, then Test Eutirox®
Participants received single oral dose of Reference Eutirox® 600 microgram (mcg) (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
干预措施: Reference Eutirox® (Drug)
Reference Eutirox®, then Test Eutirox®
Participants received single oral dose of Reference Eutirox® 600 microgram (mcg) (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
干预措施: Test Eutirox® (Drug)
Test Eutirox®, then Reference Eutirox®
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
干预措施: Reference Eutirox® (Drug)
Test Eutirox®, then Reference Eutirox®
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
干预措施: Test Eutirox® (Drug)
结局指标
主要结局
Maximum Serum Concentration in Pre Dose Corrected Data (Cmax[aj]) of Levothyroxine (T4)
时间窗: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
Cmax was obtained from the concentration time curve. Cmax\[aj\] was the maximum serum concentration in pre dose corrected data where pre dose corrected data was obtained by subtracting pre dose level of Levothyroxine (T4) from level of Levothyroxine (T4) after administration.
Area Under Serum Concentration-Time Curve From Time Zero to The Last Sampling Time in Pre Dose Corrected Data (AUC0-t [aj]) of Levothyroxine (T4)
时间窗: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
AUC0-t was defined as area under the curve of the serum concentration as a function of time, from time 0 until the last sampling time by means of the trapezoidal rule. AUC0-t \[aj\] was the area under the serum concentration-time curve from time zero to the last sampling time in pre dose corrected data where pre dose corrected data was obtained by subtracting pre dose level of Levothyroxine (T4) from level of Levothyroxine (T4) after administration.
次要结局
- Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters(Baseline up to Day 37)
- Elimination Half-Life (t1/2) of Levothyroxine (T4)(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose)
- Area Under The Curve of the Serum Concentration as a Function of Time, From Time Zero to The Last Sampling Time (AUC0-t) of Levothyroxine (T4)(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose)
- Number of Participants With Clinically Significant Abnormalities in Physical Examination(Baseline up to Day 37)
- Maximum Serum Concentration (Cmax) of Levothyroxine (T4)(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose)
- Number of Participants With Clinically Significant Abnormalities in Vital Signs(Baseline up to Day 37)
- Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)(Baseline up to Day 37)
- Time to Reach Maximum Serum Concentration (Tmax) of Levothyroxine (T4)(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose)
- Number of Participants With Adverse Events (AEs)(Baseline up to Day 51)