Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated P. Falciparum Malaria In Children In Africa

Condition(s) targeted: Malaria, Falciparum

Intervention: Azithromycin plus Chloroquine (Drug); Artemether-lumefantrine (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Pfizer

Official(s) and/or principal investigator(s):
Pfizer CT.gov Call Center, Study Director, Affiliation: Pfizer

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitologic Response (ACPR) at Day 28 in the Modified Intent-to-treat (mITT) Population

Percentage of Participants With PCR-corrected ACPR at Day 28 in Per-Protocol (PP) Population

Secondary outcome:

Percentage of Participants With PCR-corrected ACPR in the mITT Population

Percentage of Participants With PCR-corrected ACPR in PP Population

Percentage of Participants With PCR-uncorrected ACPR in the mITT Population

Percentage of Participants With PCR-uncorrected ACPR in PP Population

Percentage of Participants With Early Treatment Failure (ETF) in the mITT Population (PCR-corrected)

Percentage of Participants With ETF in PP Population (PCR-corrected)

Percentage of Participants With Late Clinical Failure (LCF) in the mITT Population (PCR-corrected)

Percentage of Participants With LCF in PP Population (PCR-corrected)

Percentage of Participants With Late Parasitologic Failure (LPF) in the mITT Population (PCR-corrected)

Percentage of Participants With LPF in PP Population (PCR-corrected)

Percentage of Participants With Asexual Parasitologic Response (PCR-corrected)

Percentage of Participants With Gametocytologic Response

Fever Clearance Time

Asexual Plasmodium Falciparum Parasite Clearance Time

Nadir Hemoglobin Level

Change From Nadir Hemoglobin Level at Days 14, 28, and 42

Time to Recurrence of Parasitemia

Number of Participants With Recurrent Parasitemia Versus Baseline Plasmodium Falciparum Chloroquine Resistance Transporter (PfCRT) Status

Percentage of Participants With PfCRT in True Failures

Minimum age: 6 Months. Maximum age: 12 Years. Gender(s): Both.

Criteria:

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;

- 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.

Pfizer Investigational Site, Nouna, Burkina Faso

Pfizer Investigational Site, Ouagadougou 01, Burkina Faso

Pfizer Investigational Site, Ouagadougou, Burkina Faso

Pfizer Investigational Site, Abidjan 13, Côte D'Ivoire

Pfizer Investigational Site, Navrongo, Ghana

Pfizer Investigational Site, Kisumu 40100, Kenya

Pfizer Investigational Site, Bamako, West Africa, Mali

Pfizer Investigational Site, Sikasso, West Africa, Mali

To obtain contact information for a study center near you, click here.

Starting date: June 2008
Last updated: May 27, 2014