Primary Objective * To characterize the potential pharmacokinetic interactions of artemether -lumefantrine, amodiaquine and primaquine in healthy adult subjects. Secondary Objectives * To characterize the pharmacokinetic properties of artemether-lumefantrine, amodiaquine and primaquine when given alone and in combination. * To evaluate the safety and tolerability of co-administered artemether-lumefantrine, amodiaquine and primaquine. * To investigate pharmacogenetic polymorphisms affecting drug levels of artemether-lumefantrine, amodiaquine and primaquine and their metabolites.
The study design is an open-label pharmacokinetic study in healthy G6PD normal Thai subjects. This study will enroll 16 healthy subjects. Participants who pass the screening process will have 6 admissions in the hospital to receive 6 drug regimens as below First admission visit: The subject may be randomized to receive either Artemether-Lumefantrine or Amodiaquine with more than 6 weeks washout period before second admission visit. Second admission visit: Subject who receives Artemether-Lumefantrine from previous visit will receive amodiaquine in this visit and vice versa. This visit will required more than 6 weeks washout period before third admission visit. Third admission visit: Every subject will receive Artemether-lumefantrine and Amodiaquine with more than 6 weeks washout period before forth admission visit. Forth admission visit: Every subject will receive Primaquine with more than 1 week washout period before fifth admission visit. Fifth admission visit: Subject may randomize to receive either Artemether-Lumefantrine and Primaquine or Artemether-Lumefantrine and Amodiaquine and Primaquine in this visit with more than 6 weeks washout period before sixth admission visit. Sixth admission visit: Subject who receives Artemether-Lumefantrine and Amodiaquine and primaquine from previous visit will receive Artemether-Lumefantrine and Primaquine in this visit and vice versa.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Artemether-lumefantrine on Day 0, 1 and 2 Washout period: more than 6 weeks
Amodiaquine on Day 0, 1 and 2 Washout period: more than 6 weeks
Artemether-lumefantrine on Day 0, 1 and 2 Washout period: more than 6 weeks
Artemether-lumefantrine + Amodiaquine on Day 0, 1 and 2 Washout period: more than 6 weeks
Primaquine on Day 0 Washout period: more than 1 week
Artemether-lumefantrine on Day 0, 1 and 2 + Primaquine on Day 0 Washout period: more than 6 weeks
Artemether-lumefantrine Day 0, 1 and 2 + Amodiaquine on Day 0, 1 and 2 + Primaquine on Day 0 Washout period: more than 6 weeks
Artemether-lumefantrine on Day 0, 1 and 2 + Primaquine on Day 0
Faculty of Tropical Medicine, Mahidol University
Bangkok, Thailand
Area under the concentration-time curve (AUC (0-∞)
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Time frame: 1 year
Area under the concentration-time curve AUC (0-last)
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Time frame: 1 year
Maximal concentration (Cmax)
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Time frame: 1 year
Elimination clearance (CL/F)
of artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Time frame: 1 year
Terminal elimination half-life (t1/2)
of artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Time frame: 1 year
Apparent volume of distribution (Vd)
of artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Time frame: 1 year
Number of adverse events
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Time frame: 1 year
Number of event concerning of abnormal electrocardiographic
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Time frame: 1 year
Number of event concerning of abnormal vital signs
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Time frame: 1 year
Number of event concerning of abnormal laboratory values
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Time frame: 1 year
Identify polymorphisms of cytochrome 450
To identify polymorphisms of cytochrome 450 related to drug metabolism from individual subject.
Time frame: 1 year
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