A Single Centre, Open-label, Parallel-group, Single Oral Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Pyrimethamine in Healthy Japanese and Caucasian Male Subjects

GlaxoSmithKline1 个研究点分布在 1 个国家目标入组 14 人开始时间: 2017年9月25日最近更新: 2020年3月27日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: GlaxoSmithKline
入组人数: 14
试验地点: 1
主要终点: Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Pyrimethamine in combination with a sulphonamide is known to be effective in the treatment of toxoplasmosis. However, Pyrimethamine has not been approved by the Japanese regulatory body (Pharmaceutical and Medical Devices Agency [PMDA]/ Ministry of Health, Labor and Welfare [MHLW]). The pharmacokinetics (PK) of Pyrimethamine has been investigated following administration of Sulfadoxine/Pyrimethamine tablet in healthy Japanese subjects. However, the study did not provide sufficient information for approval of Pyrimethamine in Japan; hence, PMDA has requested confirmation of the PK of Pyrimethamine in another PK study in Japanese and Caucasian healthy subjects. This study will be a single centre, open-label, parallel-group, single oral dose study to evaluate the PK, safety and tolerability of Pyrimethamine in healthy Japanese and Caucasian male subjects. Subjects will undergo a screening visit within 30 days prior to first dose of the study drug. On Day 1, subjects will be administered a single oral dose of pyrimethamine 50 milligrams (mg) along with calcium folinate 15 mg after an overnight fast of at least 10 hours. Subjects will continue to receive calcium folinate once daily until Day 8 of the treatment period. Blood sampling for PK analysis and safety assessments will be performed prior to dosing and over 22 days after dosing. Each subject will participate in the study for approximately 2 months from screening to follow-up.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 20 Years 至 64 Years（Adult）
性别: Male
接受健康志愿者: 是

入选标准

•Subjects should be between 20 and 64 years of age inclusive, at the time of signing the informed consent.
•Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
•Body weight >= 50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 30.0 kilogram per square meters (kg/m^2) (inclusive).
•Japanese or Caucasian male.
•A male subject must agree to use contraception during the treatment period and until follow-up.
•Japanese ethnic origin defined as having been born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Subjects should also have lived outside Japan for less than 10 years at the time of screening.
•Caucasian subject will be defined as an individual having four grandparents who are all descendants of the original people of Europe.
•Capable of giving signed informed consent which includes compliance with the requirements and restrictions of the study.

排除标准

•Alanine aminotransferase (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 percent).
•QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 milliseconds (msec).
•Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
•History 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.
•Abnormal blood pressure as determined by the investigator.
•Hematological values: outside normal range at screening.
•Serum creatinine level: outside normal range at screening visit.
•Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing.
•Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months.
•Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
•Current enrollment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research.
•Presence of Hepatitis B surface antigen (HBsAg) at screening or 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 RNA test is obtained.
•Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
•Positive pre-study drug/alcohol screen.
•Positive human immunodeficiency virus (HIV) antibody test.
•Regular use of known drugs of abuse.
•Regular alcohol consumption within 6 months prior to the study defined as: For an average weekly intake of > 14 units for males. One unit is equivalent to 10 grams (g) of alcohol: a can of mid-strength (equivalent to 375 mL) beer, 1 glass (100 mL) of table wine or 1 measure (30 mL) of spirits (including rice wine).
•History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
•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

Healthy Japanese male subjects

Experimental

Healthy Japanese male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.

干预措施: Calcium folinate (Drug)

Healthy Japanese male subjects

Experimental

干预措施: Pyrimethamine (Drug)

Healthy Caucasian male subjects

Experimental

Healthy Caucasian male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.

干预措施: Pyrimethamine (Drug)

Healthy Caucasian male subjects

Experimental

干预措施: Calcium folinate (Drug)

结局指标

主要结局

Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants