Title
A Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria
A Pilot, Double-blind, Randomized, Parallel-group, Placebo-controlled, Exploratory Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria
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.
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.
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
Patients will receive placebo for Day 1 to Day 7 and ACT (as per package instruction) for Day 1 to Day 3.
5-ALA HCl 300 mg and SFC 236 mg will be administered BID for Day 1 to Day 7 and ACT (as per package instruction) for Day 1 to Day 3. Patients will receive 5-ALA HCl+Placebo and SFC+Placebo at odd number of study medication dosing (Dose 1, 3, 5, 7, 9, 11, 13) and only 5-ALA HCl and SFC at even numbers of study medication dosing (Dose 2, 4, 6, 8, 10,12, 14).
5-ALA HCl 600 mg and SFC 472 mg will be administered QD in the morning or evening for Day 1 to Day 7 and ACT (as per package instruction) for Day 1 to Day 3. Patients will receive 5-ALA HCl and SFC at odd number of study medication dosing (Dose 1, 3, 5, 7) and placebo at even numbers of study medication dosing (Dose 2, 4, 6).
Inclusion Criteria: Male or female patients of 18 to 60 years inclusive. Weighing 35 to 90 kg. Women with child bearing potential willing to give consent for pregnancy test. Presence of symptomatic uncomplicated malaria of all species inclusive with a diagnosis confirmed by: A. Microscopically confirmed parasite infection, between 500 and 100,000 asexual parasite count/μL of blood. B. Fever, as defined by axillary/tympanic of ≥37.5°C within 24 hours before randomization (must be documented). Patients must be willing and able to give written informed consent and comply with all study visits and procedures. If a patient cannot read informed consent and/or write a signature, an impartial witness who speaks the language of the patient must be present during the entire informed consent process and discussion with the patient. Exclusion Criteria: Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization (WHO) Criteria 2010. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment. Known history of photo-hypersensitivity, porphyria, or hemochromatosis. Have taken any medication with antimalarial or antibiotic with antimalarial effect within 14 days before randomization. Received an investigational drug within the past 28 days. Patients whose Hemoglobin (Hb) level is lower than 8 g/dL. Liver function tests (aspartate aminotransferase/alanine aminotransferase [AST/ALT] levels) more than 2.5 times upper limit of normal values. Known human immunodeficiency virus (HIV) or Hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive, testing is not required. Known significant renal impairment as indicated by serum creatinine of ≥1.4 mg/dL or estimated glomerular filtration rate (eGFR) of <45 mL/min. Known history of hypersensitivity, allergic or adverse reactions to 5-aminolevulinic acid and sodium ferrous citrate. Presence or history of uncontrolled systemic disease. Female patients who are pregnant or breast-feeding. Any other condition in the opinion of the investigator makes the patient unsuitable for study Received any medication specified as contraindication for ACT or affecting blood concentration of ACT within 5 times the half-life of each medication before the first dose of study medication.
