Pharmacokinetic Study of Artemether-lumefantrine and Amodiaquine in Healthy Subjects

Launched by UNIVERSITY OF OXFORD · Sep 4, 2019

Keywords

ClinConnect Summary

This clinical trial is studying how two malaria medications, artemether-lumefantrine and amodiaquine, interact in healthy adults. The goal is to see if the combination is safe and how it behaves in the body. The study is open to 16 healthy Thai volunteers aged 18 to 60 who do not smoke and meet certain health criteria. To participate, individuals must be in good health, have no serious medical conditions, and agree to follow the study rules.

Participants can expect to take the medications during the trial and will be closely monitored by medical professionals to ensure their safety. This study is particularly important because it aims to understand how these drugs work together, which could help improve malaria treatment options in the future. It's also important to know that individuals with certain health issues, recent drug use, or who are pregnant or breastfeeding cannot participate in the trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
• • 2. Male or female non-smoker aged between 18 years to 60 years.
• 3. A female is eligible to enter and participate in this study if she is:
• • of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy
• • or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels \>40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy
• • or of childbearing potential, has a negative serum pregnancy test at screening and prior to start the study drug in each period, and agrees to abstain from sexual intercourse or use effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures
• • 4. A male is eligible to enter and participate in this study if he: agrees to abstain from sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
• • 5. Normal electrocardiogram (ECG) with QTc \<450 msec.
• • 6. Willingness and ability to comply with the study protocol for the duration of the trial.
• Exclusion Criteria:
• • 1. Females who are pregnant, trying to get pregnant, or are lactating.
• • 2. The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.
• • 3. A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
• • 4. Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes (heart failure, hypokalemia) or with a family history of long QT syndrome, Brugada syndrome, or sudden cardiac death.
• • 5. Abnormal serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) \<70 mL/min as determined by CKD-EPI equation
• • 6. History of alcohol or substance abuse or dependence within 6 months of the study.
• • 7. Use of prescription or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 times the drug half-life (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise subject safety; the investigator will take advice from the manufacturer representative as necessary.
• • 8. The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 x half-life, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
• • 9. The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample during each regimen.
• • 10. Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Note: This does not include plasma donation.
• • 11. Subjects who have a history of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• • 12. Lack of suitability for participation in this study, including but not limited to, unstable medical conditions, systemic disease manifested by tendency to granulocytopenia e.g. rheumatoid arthritis and lupus erythematosus that in the opinion of the investigator would compromise their participation in the trial.
• • 13. AST or ALT \>1.5 times the upper limit of normal (ULN)
• • 14. Subjects with history of renal disease, hepatic disease, and/or cholecystectomy
• • 15. Abnormal methemoglobin level (more than 3 mg/dL).
• • 16. History of antimalarial drugs use including but not limited to mefloquine, chloroquine, primaquine, artesunate, piperaquine and pyronaridine treatment within 6 months.
• • 17. Subject who have received quinacrine in last 30 days.