Safety and Efficacy of Imatinib in Combination With Artemether-Lumefantrine for Uncomplicated Malaria

Inclusion Criteria:

For Part 1 and 2 of the study design, all individuals must meet all the inclusion criteria below:

• Patients diagnosed with symptomatic mild to moderate P. falciparum malaria with a parasite density of >= 5000 parasites/μl
• Adult male, age 18-55 years old or adult female, age 18-55 years that are post-menopausal, or test negative on a pregnancy test and will be on active birth control through to the end of the follow up period.
• Provision of informed consent and agrees to hospital admission for 48-72hrs
• Good health condition other than malaria
• The patient has not taken anti-malarial drugs in the past 4 weeks

For Part 3 of the trial, all individuals must meet all the inclusion criteria below:

• Patients diagnosed with symptomatic mild to moderate P. falciparum malaria and a parasite density of >= 5000 parasites/μl
• Age 12 months to below 18 years
• Presented by parent or legally accepted representative (LAR) who has consented to the participation of the child in the trial and agrees to hospital admission for 48-72hrs.
• Hb levels > 5mg/dL
• Child has not taken anti-malarial drugs in the past 6 weeks.

Exclusion Criteria:

• Prospective study participant, LAR and/or impartial witness (where applicable) declines to provide informed consent.

• Symptoms and signs of severe or complicated malaria including:

  • significant confusion or impaired consciousness (including unarousable coma)
  • multiple convulsions (more than two episodes within 24 hours),
  • respiratory distress
  • circulatory collapse (systolic blood pressure <80mm Hg with evidence of impaired perfusion)
  • clinical jaundice plus evidence of other vital organ dysfunction
  • simultaneous infection of unrelated origin
• Parasite density > 200,000 parasites /μl
• In the case of female participants: currently pregnant or lactating
• Other neurological or psychiatric symptoms or disorders
• Abnormal bleeding
• Resting heart rate lower than 55 or higher than 100 bpm
• History of cardiac disease
• Signs, symptoms and laboratory results of impairment of vital organs such as liver, lungs, kidney and cardiovascular system

• Abnormal blood chemistry:

  • hemoglobin < 9.0 g/dL in adults or < 5.0 g/dL in children 12 months-18 years
  • WBC not in the range of 4800-10,000/mm3
  • RBC if < 4.0x106/ mm3
  • Platelet < 1.3x105/ mm3
  • ALAT not in the normal range (4 to 36 U / l)
  • ASAT not in the normal range (8 to 33 U / l)
  • Total bilirubin 0.1 to 1.2 mg / 100 ml
  • Serum protein if < 5.5 g/dL
• Symptoms and signs of infection such as pneumonia, dengue fever, and other viral or bacterial infection.
• Patients with symptoms of gastrointestinal infections or any sign of malabsorption that may interfere with drug absorption.
• Concomitant infection by plasmodium species other than P. falciparum
• Inability to attend/meet study staff on follow up visits

• Concomitant use of medicines, including:

  • medicines used to treat high cholesterol (such as atorvastatin, lovastatin, simvastatin);
  • medicines used to treat hypertension and heart problems (such as diltiazem, nifedipine, nitrendipine, verapamil, felodipine, amlodipine);
  • medicine used to treat HIV (antiretroviral medicines) including protease inhibitors (such as amprenavir, atazanavir, indinavir, nelfinavir, ritonavir), non-nucleoside reverse transcriptase inhibitors (such as efavirenz, nevirapine);
  • medicines used to treat microbial infections (such as telithromycin, rifampicin, dapsone);
  • medicines used to help you fall asleep: benzodiazepines (such as midazolam, triazolam, diazepam, alprazolam), zaleplon, zolpidem;
  • medicines used to prevent/treat epileptic seizures including barbiturates (such as phenobarbital), carbamazepine or phenytoin;
  • medicines used after organ transplantation and in autoimmune diseases (such as cyclosporin, tacrolimus);
  • nefazodone (used to treat depression);
  • aprepitant (used to treat nausea);