This is a pilot, double-blind, randomized, parallel-group, placebo-control, exploratory study to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride (5-ALA HCl) and sodium ferrous citrate (SFC) added on artemisinin-based combination therapy (ACT) compared with ACT alone in the treatment of malaria. Patients who are suffering from uncomplicated malaria, are eligible for randomization.The study will be conducted in a total of 75 patients with uncomplicated malaria.
Approximately 75 patients will be randomized in a 1:2:2 ratio to 3 arms: Arm 1: placebo+ACT group (15 patients) Arm 2: 5 ALA/SFC+Placebo+ACT twice daily (BID) (30 patients) Arm 3: 5-ALA/SFC+Placebo+ACT once daily (QD) (30 patients) The study duration will be a maximum of 98 days with treatment period of 7 days and follow-up period of 91 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
5-ALA HCl 150 mg capsules will be given to the patients as 600 mg QD
SFC 118 mg capsules will be given to the patients as 472 mg QD
Tablets of ACT will be administered following Dosage and Administration in the package insert of ACT. ACT will be supplied as a combination tablet.
Number of patients with adverse events
Number of patients with any adverse events or clinically significant abnormal laboratory parameters to investigate safety and tolerability of 5-ALA HCl and SFC in simultaneous administration with ACT.
Time frame: From screening visit (Day -1) untill the Follow-up Visit (Day 98)
Cure rate on Day 28
Cure rate is defined as the proportion of patients with polymerase chain reaction (PCR)-corrected Adequate Clinical and Parasitological Response (ACPR). PCR-corrected ACPR is defined as patients with clearance of asexual parasites within 28 days of initiation of study medication and without recrudescence within 28 days. Cure rate to investigate the preliminary efficacy of 5-ALA HCl and SFC in simultaneous administration with ACT.
Time frame: Day 28
Parasite Clearance Time
Time from first dosing to time of first of 4 consecutive readings with zero parasite count in blood. Calculated based on parasite count in blood every 4 hours after the start of study medication for 72 hours until there are 4 consecutive negative readings.
Time frame: Every 4 hours for 72 hours from Day 1 to Day 7 until 4 consecutive negative readings
Fever Reduction Time
Time to Fever Reduction is defined as the time from first dosing to first normal reading of temperature (\<37.5 °C) for two consecutive normal temperature reading plus confirmed normal temperature every 4 hours after the start of study medication for 72 hours
Time frame: Every 4 hours for 72 hours from Day 1 to Day 7
Gametocyte Clearance Time
Time from the first dose until first total and continued disappearance of gametocytes which remains at least a further 24 hours
Time frame: Day 1 to Day 7 + 24 hours
Change in inflammatory parameter: C-reactive protein
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Matching placebo capsules to 5-ALA HCl and SFC will be administered to the patients
5-ALA HCl 150 mg capsules will be given to the patients as 300 mg BID
SFC 118 mg capsules will be given to the patients as 236 mg BID
Change from baseline in C-reactive protein to investigate change in inflammatory parameters
Time frame: Days 1, 3, 7, and 28
Change in inflammatory parameter: interleukin-6
Change from baseline in interleukin-6 to investigate change in inflammatory parameters
Time frame: Days 1, 3, 7, and 28
Change in inflammatory parameter: tumor necrosis factor (TNF)-alpha
Change from baseline in tumor necrosis factor (TNF)-alpha to investigate change in inflammatory parameters
Time frame: Days 1, 3, 7, and 28
Change in iron metabolism: Serum iron
Change from baseline in serum iron to investigate change in iron metabolism parameters
Time frame: Days 1, 3, 7, 28, and 98
Change in iron metabolism: Hepcidin
Change from baseline in hepcidin to investigate change in iron metabolism parameters
Time frame: Days 1, 3, 7, 28, and 98
Change in iron metabolism: total iron binding capacity (TIBC)
Change from baseline in total iron binding capacity (TIBC) to investigate change in iron metabolism parameters
Time frame: Days 1, 3, 7, 28, and 98
Change in iron metabolism: unsaturated iron binding capacity (UIBC)
Change from baseline in unsaturated iron binding capacity (UIBC) to investigate change in iron metabolism parameters
Time frame: Days 1, 3, 7, 28, and 98