CompletedPhase 1

Phase I Study of Pyrimethamine in Healthy Japanese and Caucasian Subjects

Australia14 participantsStarted 2017-09-25

Plain-language summary

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.

Who can participate

Age range20 Years – 64 Years

SexMALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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. Exclusion Criteria: * 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…

What they're measuring

Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants

Timeframe: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

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

Timeframe: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

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

Timeframe: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants

Timeframe: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants

Timeframe: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants

Timeframe: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22

Trial details

NCT IDNCT03258762

SponsorGlaxoSmithKline

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2017-11-19

Results submitted2018-11-16

View on ClinicalTrials.gov More Toxoplasmosis trials