Pharmacokinetics of Sulfadoxine-pyrimethamine Plus Amodiaquine for Intermittent Preventive Treatment in Children (IPTc)
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The aim of the study is to determine the pharmacokinetic profile of sulfadoxine-pyrimethamine
      plus amodiaquine (SP+AQ) when used for seasonal Intermittent Preventive Treatment (IPT) to
      prevent malaria in children aged 3 to 59 months in Lamarame, NDoffane District, Senegal.
      Several studies have shown that seasonal IPT in children can provide a high degree of
      protection against clinical malaria. SP+AQ is the most effective regimen. However little is
      known about the pharmacokinetics of amodiaquine and sulfadoxine-pyrimethamine in children.
      The purpose of this study is to determine the pharmacokinetics profile of SP+AQ when used for
      IPT in Senegalese children. 150 children aged 3 to 59 months will be enrolled in November.
      They will receive a therapeutic dose of sulfadoxine-pyrimethamine and amodiaquine, and will
      be followed up for 30 days. Four finger prick blood samples will be taken from each child for
      PK analysis.
    

Detailed description: 
      SP+AQ is the most effective regimen for IPT in children, but there is little information
      about the pharmacokinetics of these drugs in children. Although this combination has been
      used for many years for treatment of clinical malaria there have been no studies of the
      pharmacokinetics of this combination. A recent study described the pharmacokinetics of
      amodiaquine when used in combination with artesunate to treat children with clinical malaria
      (Stepniewska et al, 2009), and another recent study described the pharmacokinetics of SP in
      children with malaria (Barnes et al, 2006), and a further study of SP in children with
      uncomplicated malaria demonstrated a low plasma level of the drug in children who failed the
      treatment (Obua et al. 2008), but there are no studies of these drugs given together or in
      healthy children. This information is important in order to check the bioavailability of the
      two drugs when used for IPT and to check the adequacy of the currently recommended dosage.
      The study will be conducted in a rural district of Senegal, after holding community meetings
      to explain the study. 150 children aged 1-5 years, boys and girls who do not have history of
      allergy to study drugs and whose parents agreed for them to participate will be enrolled at
      the study clinic. The sample size determination is based on experience from other PK studies.
      During the study organization phase, meetings will be held at the health facilities, members
      of the community, community leaders, and health staff will be invited to attend, the
      investigators will explain, in local language, the aims of the study, the recruitment and
      follow up procedures, the total sample size needed, and the duration of follow up. The
      detailed schedule for blood sampling will be explained. Subsequently the investigators will
      visit families at home to explain the study and invite people to attend at the clinic.
      Mothers or carers will be asked to bring the child to the clinic where, after signing to
      indicate consent, the child will be weighed and have a clinical examination, a finger prick
      blood sample will be taken by drawing blood into a vacutainer, from which 70µL of blood will
      be pipetted onto filter paper. SP and the first dose of AQ will be administered according to
      the child's weight, the child will be kept under observation for 30 minutes before being
      allowed to return home. The remaining doses of amodiaquine (days 1 and 2) will be given to a
      field worker who will visit the child at home to supervise drug administration. The exact
      time of the administration will be recorded. Any child who vomits a dose will be given a
      repeat dose. The child will be asked to provide a finger prick blood sample on three further
      occasions between day 1 and day 28, determined according to a schedule chosen to allow good
      estimation of PK parameters. Trained field staff will visit each child on day 4, to ask about
      any adverse reactions to the drugs, and on day 14 and 28 to check the child is well. Children
      with signs of severe malaria, or any other severe illness, will be referred immediately to
      the health post. For other children, if the child has axillary temp >=37.5oC or a history of
      fever in the last 48 hours a finger prick blood sample will be taken for malaria diagnosis by
      rapid test and blood film to be read later. Children with a positive test will be treated
      with Coartem.
    

Intervention name(s): sulfadoxine-pyrimethamine plus amodiaquine
Intervention type(s): Drug
Intervention description(s): one dose of sulfadoxine-pyrimethamine 25/1.25 mg/kg plus three daily doses of amodiaquine, 10 mg/kg/day
Intervention MeSH terms: Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: IPTc; malaria; children; pharmacokinetics; amodiaquiane; sulfadoxine-pyrimethamine