An Open-label, Randomised, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of SKF101804 Cefixime 200 mg/5 mL Suspension Versus Cefixime 200 mg/5 mL Suspension Reference Product in Healthy Adult Participants Under Fasting Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC [0-t]) for Cefixime
研究概览
简要总结
This study is open-label, randomized two-way cross-over study to determine if cefixime 200 mg/5 mL powder for suspension (test formulation: SKF101804) is bioequivalent to cefixime 200 mg/5 mL suspension reference formulation. Study will be conducted in 28 healthy adult subjects under fasting conditions. There will be two treatment periods and each subject will participate in both periods. The washout period between both treatment periods will be 7-14 days. Subjects will be randomized to either of treatment sequences of reference followed by test or test followed by reference to receive a single dose of test or reference formulation on Day 1 in each treatment period. The study will last for 5 to 7 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Subject must be healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- •A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included at investigator discretion in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Subject with a body weight 50 kilogram (kg) and body mass index (BMI) within the range 19-30 kilogram per meter square (kg/m^2) (inclusive).
- •A healthy male subject must agree to use contraception during the treatment period and for at least 5 days after the last dose of study treatment and refrain from donating sperm during this period.
- •A female subject is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
- •A subject should be capable of giving signed informed consent.
排除标准
- •Subject with history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- •Subjects with any other condition that is capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- •Subject with abnormal renal function, as determined by creatinine clearance and considered as clinically significant by the investigator will be excluded.
- •Subject with abnormal blood pressure (BP) as determined by the investigator.
- •Subject with lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- •Subject who had breast cancer within the past 10 years.
- •ALT >1.5 times upper limit of normal (ULN).
- •Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •Subject with current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Subject with history of colitis
- •Subject with history of cephalosporin induced hemolytic anemia.
- •QT interval corrected for heart rate according to Bazett's formula (QTcB) >450 milliseconds (msec). Subjects with a known risk of QT prolongation will be excluded.
- •Past or intended use of over-the-counter or prescription medication including herbal medications, within 14 days prior to dosing unless in the opinion of the investigator and sponsor, the medication will not interfere with the study.
- •Participation in the study would result in loss of blood or blood products in excess of 500 mL within 90 days.
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •Current enrolment or past participation within the last 90 days before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
- •Presence of Hepatitis B surface antigen (HBsAg) at screening. Positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
- •Positive pre-study drug/alcohol screen.
- •Positive human immunodeficiency virus (HIV) antibody test.
- •Regular use of known drugs of abuse.
- •Subjects with regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- •Subjects with urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- •Subjects who are sensitive to heparin or heparin-induced thrombocytopenia.
- •Subjects with known sensitivity to any drugs from the class of cephalosporin, or components thereof.
- •Subjects with known sensitivity to any drugs from the class of penicillin, or components thereof.
- •Subjects with known sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
研究组 & 干预措施
Test followed by Reference Formulation
Subjects will be randomized to receive single dose of Test formulation (SKF101804: cefixime 200 mg/ 5 mL) on Day 1 of the treatment period 1 and Reference formulation (cefixime 200 mg/5 mL) on Day 1 of the treatment period 2. There will be wash out period of 7-14 days between the two treatment periods.
干预措施: Test formulation A (Drug)
Test followed by Reference Formulation
Subjects will be randomized to receive single dose of Test formulation (SKF101804: cefixime 200 mg/ 5 mL) on Day 1 of the treatment period 1 and Reference formulation (cefixime 200 mg/5 mL) on Day 1 of the treatment period 2. There will be wash out period of 7-14 days between the two treatment periods.
干预措施: Reference formulation B (Drug)
Reference followed by Test Formulation
Subjects will be randomized to receive single dose of Reference formulation (cefixime 200 mg/5 mL) on Day 1 of the treatment period 1 and Test formulation (SKF101804: cefixime 200 mg/ 5 mL) on Day 1 of the treatment period 2. There will be wash out period of 7-14 days between the two treatment periods.
干预措施: Test formulation A (Drug)
Reference followed by Test Formulation
Subjects will be randomized to receive single dose of Reference formulation (cefixime 200 mg/5 mL) on Day 1 of the treatment period 1 and Test formulation (SKF101804: cefixime 200 mg/ 5 mL) on Day 1 of the treatment period 2. There will be wash out period of 7-14 days between the two treatment periods.
干预措施: Reference formulation B (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC [0-t]) for Cefixime
时间窗: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0 8.0, 10.0, 12.0, 16.0 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of cefixime under fasted state. Pharmacokinetic analysis of cefixime was conducted using non-compartmental methods. Pharmacokinetic Population comprised of participants who completed the study and for whom primary pharmacokinetic parameters could be calculated for all treatment periods were included in the statistical pharmacokinetic analysis of the study.
Maximum Observed Plasma Concentration (Cmax) Within a Participant Across All Treatments of Cefixime
时间窗: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0 8.0, 10.0, 12.0, 16.0 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of cefixime under fasted state. Pharmacokinetic analysis of cefixime was conducted using non-compartmental methods.
次要结局
- Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to (AUC [0-infinity]) Across All Treatments for Cefixime(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0 8.0, 10.0, 12.0, 16.0 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period)
- Terminal Phase Half-life (T1/2) for Cefixime(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0 8.0, 10.0, 12.0, 16.0 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period)
- Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Blood Urea Nitrogen (BUN) at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Total Protein at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Mean Corpuscular Volume (MCV) at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), and Aspartate Aminotransferase (AST) at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Erythrocyte Count at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Number of Participants With Potential Clinical Importance (PCI) Abnormal Findings for Urinalysis(Day -1 and Day 2 of each treatment period)
- Time of Occurrence of Cmax (Tmax) for Cefixime(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0 8.0, 10.0, 12.0, 16.0 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period)
- Percentage of AUC(0-infinity) Obtained by Extrapolation (%AUCex) for Cefixime(Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0 8.0, 10.0, 12.0, 16.0 and 20.0 hours post dose on Day 1, 24.00 hours post dose on Day 2 of each treatment period)
- Calcium, Glucose, Potassium and Sodium at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Total Bilirubin (Total Bil), Direct Bilirubin (Direct Bil) and Creatinine (Creat) at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points(Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period)
- Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE)(Up to Day 16 in each treatment period)
- Hematocrit at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Percent Reticulocytes at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Respiratory Rate at Indicated Time-points(Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period)
- Body Temperature at Indicated Time-points(Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period)
- Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points(Day -1 and Day 2 of each treatment period)
- Pulse Rate at Indicated Time-points(Day 1 Pre-dose 1.5 hours, Day 1 post-dose 2, 4, and 6 hours and Day 2 post-dose 24 hours of each treatment period)