Healthy volunteer study Chemicals and Drugs [D]
Conditions
Interventions
Artesunate 2.4 mg/kg ,Artesunate 2.4 mg/kg ,Artesunate 2.4 mg/kg ,Artesunate 2.4 mg/kg
Experimental Drug,Experimental Drug,Active Comparator Drug,Active Comparator Drug
Intravenous administration of test formulation,Intramuscular administration of test formulation,Intravenous administration of reference formulation,Intramuscular administration of reference formulatio
Sponsors
Guilin Pharmaceutical (Shanghai) Co., Ltd.
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1)Healthy male and female subjects aged 18-55 years 2)Body mass index of 18-25 kg/m2 3) No evidence of underlying disease, physically or mentally disabled or clinically significant abnormal finding during screening and/or medical history examination 4)A female is eligible to 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 • of non-childbearing potential including post-menopausal females 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 post-surgical bilateral oophorectomy with or without hysterectomy, or • of childbearing potential, but has a negative serum pregnancy test at screening and prior to study drug administration in each period, and willingness to abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study period until completion of the follow-up procedures 5)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 is willing to use a condom/spermicide during the study until completion of the follow-up procedures 6)Normal ECG with Fridericia-corrected QT (QTcF) and Bazett-corrected QT (QTcB) intervals < 450 msec 7)Willing to participate in this study and sign the Informed Consent Form
Exclusion criteria
Exclusion criteria: 1)Any history of hypersensitivity to artesunate or known hypersensitivity to any component of the formulations 2)History of abnormal bleeding after minor injury or prolong hematoma following the intramuscular injection 3)Family history of any bleeding tendency 4)Platelet upper normal limit or INR > 1.5 6)AST or ALT > 1.5 ULN 7)Creatinine clearance (CLcr) <70 mL/min as determined by Cockcroft-Gault equation 8)Personal and/or family history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, risk factors for torsades de points (heart failure, hypokalaemia), or with a family history of sudden cardiac death 9)Administration of a known drug that can cause damage to organs or other medicinal products known to prolong the QT interval (e.g. mefloquine, halofantrine, lumefantrine, chloroquine, quinine, and piperaquine) in the preceding 3 months prior to the start of the study 10)Participation in a clinical trial or receiving a prescription drug, non-prescription drug or a new chemical entity within 30 days, 5 half-lives or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication 11)Donation of blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Plasma or blood donation during the study is not acceptable 12)HIV, HBV, or HCV positive 13)Malaria positive 14)History of alcohol or substance abuse or dependence 15)Unwillingness 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 16)Receiving any form of anticoagulant within 14 days prior to start study drug, plan to receive any form of anticoagulant while participating in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Artesunate and DHA concentration in plasma Frequent sampling for 24 hours post dose AUC0-∞ and AUC0-LAST, CMAX, CL, T1/2, TMAX, Vd | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability Frequent measurements for 24 hours post dose Vital signs, and ECG measurements ,Laboratory evaluations Before drug administration and before discharge in each study occasion Biochemistry and Haematology ,Adverse effects includes dizziness, light-headedness, rash and tasted alteration After drug administration throughout the study period Physical examination | — |
Contacts
Public ContactProfessor Joel Tarning
Mahidol-Oxford Tropical Medicine Research Unit
Outcome results
None listed