Health Condition 1: null- Acute uncomplicated Plasmodium falciparum malaria
Conditions
Interventions
Intervention1: Fixed dose combination of dispersible tablets of arterolane maleate and piperaquine phosphate: Each dispersible tablet consists of arterolane maleate 37.5 mg and PQP 187.5 mg in a fixed
Sponsors
Ranbaxy Laboratories Limited
DST Govt of India
Eligibility
Inclusion criteria
Inclusion criteria: Patients must fulfill the following inclusion criteria to be eligible for enrollment into the study: 1. Children of either gender aged between 6 months to 12 years, both inclusive. 2. Minimum body weight of 5 kg. 3. Able to take drugs under study by the oral route 4. Absence of severe malnutrition (defined as a child whose weight-for-height is below -3 standard deviation or less than 70% of the median of the NCHS/ WHO normalized reference values or who has symmetrical oedema involving at least the feet4,5 ) 5. Minimum Hemoglobin (Hb) level of > 8 gm/dL. 6. Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum parasites only. 7. Initial parasite densities appropriate for inclusion will be between 1,000 and 100,000 asexual parasites/µL blood (both inclusive). 8. Presence of fever (axillary temperature >= 37.5 °C) or a history of fever in the past 24 hours. 9. Written informed consent, provided by parent/guardian in accordance with local practice. If parent/ guardian is unable to provide informed consent in writing, a thumbprint to indicate consent in the presence of at least one witness is acceptable. 10. Willingness and ability to comply with the study protocol for the duration of the study. 11. Patient resides within a reasonable distance of the investigational site, so that attendance of all study visits and follow-up by medical staff are logistically feasible.
Exclusion criteria
Exclusion criteria: If any of the following conditions apply, the patient should not be enrolled in the study. 1.Known allergy to artesunate, artemether, artemisinin derived products, piperaquine or any other related drug. 2.Infants with a history of hyperbilirubinemia during the neonatal period 3.Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the World Health Organization (WHO) list of essential drugs 4.Evidence of any concomitant infection at the time of presentation (including P. vivax, P. ovale and P. malariae) 5.Any other underlying disease that may compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis, bacterial infection; cardiac or pulmonary disease) 6.Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carini pneumonia in children born to HIV+ women. 7.Patients with severe malaria as per WHO criteria 2003. 8.Presence of general danger signs of severe malaria among children <5 years old (as per WHO) 9.Female patients between the age group of 8 to 12 years (both inclusive) who are pregnant at screening. The selection of the candidate for pregnancy screening test would be as per the judgement of the Investigator. 10.Female patients between the age group of 8 to 12 years (both inclusive) who are lactating at the time of screening. 11.Any antimalarial treatment during 1 month prior to screening, as assessed by medical history 12.Participation in any investigational drug study during the 30 days prior to screening. 13.Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management. These abnormalities include QTc interval > 450 msec at screening and cardiac conduction disorders, with the exception of right bundle branch block. 14.Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhea defined as > 3 episodes of watery stools in the previous 24 hours or patients who have had 3 episodes of vomiting within 24 hours prior to screening). 15.Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at screening: Serum creatinine > 1.5 × upper limit of normal (ULN). Aspartate transaminase > 2.5 × ULN. Alanine transaminase > 2.5 × ULN. Serum bilirubin > 3 mg/dL. 16.Patients who have had a splenectomy as confirmed by history or clinical examination. 17.Patients with known history of human immunodeficiency virus (HIV) infection or other immunosuppressive disorders. 18.Evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied). 19.Patients who have epilepsy or a history of convulsions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| â?¢ To estimate the Day 28 PCR corrected Adequate Clinical and Parasitological Response (ACPR) of three dose regimen of fixed dose combination (FDC) dispersible tablets of arterolane maleate and PQPTimepoint: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Cure rate (ACPR) on Day 42. PCT. FCT. Proportion of patients with PCR-uncorrected ACPR on Day 28. Gametocyte count on Days 0, 7 (±1), 14(±1), 21(±2) 28(±2), 35(±2) and 42 (±2) PK parameters of arterolane and piperaquine: Cmax, Tmax, AUC, Cl/ F, Vd/F, t1/2 and additional PK model dependant parameters Incidence of adverse events or clinically significant changes in laboratory parameters, physical examination, ECG, or vital signs. Timepoint: Days 0, 7 (±1), 14(±1), 21(±2) 28(±2), 35(±2) and 42 (±2) | — |
Countries
Cote d'Ivoire, India, Rwanda
Contacts
Public ContactDr Nilanjan Saha
Head-Clinical Pharmacology and Development
Outcome results
None listed