Official Title: “Phase 2/3, Open-Label, Comparative Trial Of Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In Children In Africa”

The primary objective is to confirm the hypothesis that azithromycin used in combination with chloroquine is non-inferior to artemether- Lumefantrine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum in children in African countries.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2009

Intervention(s) in this Clinical Trial

• Drug: Azithromycin plus Chloroquine
  • Combination of Azithromycin plus Chloroquine Azithromycin (~30 mg/kg) + chloroquine (~10mg base /kg) combination tablet(s) on weight basis, once daily for 3 days (Days 0,1,2) or Artemether-lumefantrine tablet(s) based on weight and labeling for 3 days (Days 0, 1, 2)
• Drug: Chloroquine
  • chloroquine (~10mg base /kg) combination tablet(s) on weight basis, once daily for 3 days (Days 0,1,2)
• Drug: Artemether-lumefantrine
  • Artemether-lumefantrine tablet(s) based on weight and labeling for 3 days (Days 0, 1, 2)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2

Primary Measures

• The primary endpoint is based on the proportion of subjects with Adequate Clinical & Parasitologic Response (ACPR; PCR corrected, determining recrudescence or reinfection) at Day 28 .
  • Time Frame: during the study
    Safety Issue?: No
• The primary objective is to confirm azithromycin plus chloroquine vs. artemether-lumefantrine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum in children in African countries.
  • Time Frame: during the study
    Safety Issue?: No

Secondary Measures

• Asexual P. falciparum parasite clearance rate at 7, 14, 21, 35 and 42 days; Asexual P. falciparum parasite clearance time;
  • Time Frame: during the study
    Safety Issue?: No
• P. falciparum gametocyte absence rate at 7, 14, 21, 28, 35 and 42 days;
  • Time Frame: during the study
    Safety Issue?: No
• Fever clearance time;
  • Time Frame: during the study
    Safety Issue?: No
• Hematologic recovery among subjects anemic at nadir from Day 0, Day 1, Day 2, or Day 3;
  • Time Frame: during the study
    Safety Issue?: No
• Safety of all study regimens;
  • Time Frame: during the study
    Safety Issue?: No
• Time to recurrence of parasitemia; Recurrent parasitemia vs. PfCRT status at Baseline;
  • Time Frame: during the study
    Safety Issue?: No
• % PfCRT in true failures.
  • Time Frame: during the study
    Safety Issue?: No
• Secondary objectives include the assessment of the safety, efficacy, and tolerability of all treatment regimens.
  • Time Frame: during the study
    Safety Issue?: No
• % of subjects with Early Treatment Failure (ETF), Late Clinical Failure (LCF, PCR corrected), Late Parasitologic Failure (LPF, PCR corrected)
  • Time Frame: during the study
    Safety Issue?: No

Inclusion Criteria:

• Girls and boys ≥5 years to ≤12 years (Cohort 1); and ≥6 to ≤59 months of age (Cohort 2) with uncomplicated, symptomatic malaria as indicated by the presence of the following:
• Blood smears positive for monoinfection with P. falciparum and asexual parasitemia between 1000 -100,000 parasites/µL;
• Documented fever (38.0°C/100.4°F rectal or tympanic; 37.2°C/99.0°F axillary or 37.5°C/99.5°F oral) or history of fever (as reported by the legally acceptable representative) within the prior 24 hours;
• Appropriate for outpatient treatment;
• Blood glucose ≥60 mg/dL;
• Hemoglobin ≥6 g/dl or hematocrit ≥18% without signs of anemia-induced Congestive Heart
• Failure (CHF);
• Negative urine pregnancy test for females ≥10 years of age (and of child bearing potential)

Exclusion Criteria:

• Peripheral blood smear positive for mixed infection with multiple Plasmodium spp.
• Severe or complicated malaria including subjects with any of the following:
• Impaired consciousness (eg, obtundation, unarousable coma), seizures or abnormal neurologic exam suggestive of severe or complicated malaria;
• Known hemoglobinuria;
• Jaundice;
• Respiratory distress;
• Persistent vomiting;
• Gross hematuria, as reported by the subject's legally acceptable representative;
• Inability to drink or breastfeed;
• Unable to sit or stand as appropriate for age;
• Recent history of convulsions;
• Inability to drink or breastfeed;
• Unable to sit or stand as appropriate for age;
• Known pregnancy or breast-feeding or positive urine pregnancy test (females ≥10 years of age and of child bearing potential);
• History of allergy to or hypersensitivity to azithromycin, any macrolide, chloroquine, artemether, any artemisinin derivative, lumefantrine;
• Any contraindication to any study drug including AZ, CQ and AL;
• History of treatment with any antimalarial drug (such as halofantrine, chloroquine, quinine, mefloquine, Malarone, SP, artemisinin compounds) or antibacterial with known antimalarial activity (macrolides, doxycycline, clindamycin) within 2 weeks prior to enrollment of a subject (and/or of the mother of a subject who is being breastfed) into the study;
• Known or suspected cardiovascular, hepatic or renal abnormality that in the opinion of the investigator would place the subject at increased risk to participate in the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Months

Maximum Age for this Clinical Trial: 12 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Pfizer

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Overall Contact: Pfizer CT.gov Call Center 1-800-718-1021 

Information obtained from ClinicalTrials.gov on August 21, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00677833

Study ID Number: A0661157

ClinicalTrials.gov Identifier: NCT00677833

Health Authority: United States: Food and Drug Administration

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