Evaluation of Fosmidomycin and Clindamycin in the Treatment of Acute Uncomplicated P.Falciparum Malaria in Children
Condition: Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open label uncontrolled study to determine the efficacy of fosmidomycin and
      clindamycin when co-administered orally over three days in the treatment of acute
      uncomplicated Plasmodium falciparum malaria in children.

      The primary study endpoints will be the cure rate on Day 28 (PCR corrected). The secondary
      endpoints will be the cure rate on Day 7 and the parasite and fever clearance times.
    

Detailed description: 
      An open label uncontrolled study to determine the efficacy of fosmidomycin and clindamycin
      when co-administered orally over three days in the treatment of acute uncomplicated
      Plasmodium falciparum malaria in children.

      The primary study endpoints will be the cure rate on Day 28 (PCR corrected). The secondary
      endpoints will be the cure rate on Day 7 and the parasite and fever clearance times.

      Study population A total of 40 children will be recruited into the study. Sample size
      calculations have been made on the basis that this trial aims at substantiating the efficacy
      results obtained in children in Gabon. In the largest trial of this drug combination done in
      Gabon, 51 children were recruited, and the per-protocol, PCR-adjusted day 28 cure rate was
      89% (42/47; 95% CI, 77 to 96%). Based on this expected 90% efficacy estimate, a sample size
      of 35 children produces a two-sided 95% confidence interval with a an estimated precision of
      20%.

      Allowing for an attrition rate of 10% for non-evaluable subjects, a sample size of 40
      subjects will be required.

      Study endpoints Primary The primary endpoint will be the cure rate on Day 28 (PCR corrected).
      Secondary The secondary endpoints will be the cure rate on Day 7 and the parasite and fever
      clearance times.

      Withdrawal criteria during treatment (classified as therapeutic failure)

        -  Severe deterioration in clinical condition

        -  Signs of severe malaria, according to WHO criteria

        -  Onset of drug related serious adverse events

        -  Repeated vomiting within one hour of re-dosing

      Discontinuation criteria after completion of treatment (classified as therapeutic failure)

        -  Persistent parasitaemia at 96 hours after initiation of treatment

        -  Parasitaemia during follow-up period after initial clearance

        -  No reduction of parasitaemia within 48 hours after initiation of treatment

        -  Onset of drug related serious adverse events

      Discontinuation criteria after completion of treatment (not classified as therapeutic
      failure)

        -  Withdrawal of guardian consent

        -  Loss to follow up

        -  Protocol violation Procedure for treatment The study drugs will be administered under
           direct supervision by a study clinician or nurse in doses of fosmidomycin 30mg/kg/dose +
           clindamycin 10mg/kg/dose twice daily for three days (total daily dose fosmidomycin
           60mg/kg, clindamycin 20mg/kg).

      In the event of vomiting within one hour of dosing, the same dose of each drug will be
      re-administered from a supplemental drug supply.

      Re-dosing will be done only once for each drug administration and only twice for the whole of
      the treatment period.

      Concomitant treatment Subjects will be treated for symptoms and adverse events during the
      study period by standard treatment.

      Drugs with antimalarial activity or likely to have an effect on parasitaemia will not be
      permitted during the study. This will include artemether-lumefantrine combination,
      artesunate, sulfadoxine/pyrimethamine combination, chloroquine, amodiaquine and
      co-trimoxazole.

      Trial procedures and duration of the study A general physical examination will be performed
      on admission to the study. All subjects will be hospitalised for a minimum of three days
      until they are asymptomatic and aparasitaemic.

      Brief examinations will be conducted daily during this period and once weekly thereafter to
      assess general physical status.

      Thereafter subjects will return for out-patient follow-up on days 7 ± 1 day, 14 ± 2 days, 21
      ± 2 days and 28 ± 2 days.

      All subjects are expected to participate in the trial for the total duration of 28 days.

      Those subjects not attending for follow-up will be located by a member of the study staff who
      will provide transportation to the hospital for the scheduled examinations or ascertain the
      reason for failing to attend.
    

Intervention name(s): Fosmidomycin and Clindamycin co-administration
Intervention type(s): Drug
Intervention description(s): Fosmidomycin sodium syrup at a concentration of 250mg/5ml and clindamycin hydrochloride syrup at a concentration of 75mg/5ml. Administered in doses of fosmidomycin 30mg/kg/dose + clindamycin 10mg/kg/dose twice daily for three days (total daily dose fosmidomycin 60mg/kg, clindamycin 20mg/kg)
Intervention MeSH terms: Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Fosmidomycin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Malaria