Clinical Trial: Safety and Tolerability of Low Dose Primaquine

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Tolerability and Safety of Low Dose Primaquine for Transmission Blocking in Symptomatic Falciparum Infected Cambodians

Brief Summary:

In Cambodia, falciparum is becoming more difficult to treat because drugs are becoming less effective. The investigators can help to try to prevent the spread of this resistant malaria by adding a drug that will make it more difficult for the mosquito to drink up the malaria in people's blood. If the mosquito cannot drink up the malaria, then the malaria cannot develop in the mosquito so it will not be able to inject malaria back into people when it bites. The drug the investigators will use is called primaquine.

Primaquine commonly causes the red cells in the blood to break apart if they are weak. Red cells need enzymes to work properly and weak red cells have low amounts of an enzyme called glucose 6 phosphate dehydrogenase (G6PD). The investigators want to know if treating malaria with primaquine will be safe for the red cells. To do this study, the investigators need to know if a subject has low G6PD or not.


Detailed Summary:
Sponsor: Malaria Consortium

Current Primary Outcome: Haemoglobin concentration [ Time Frame: Day 7 ]

Compare haemoglobin concentrations in g/dL between the G6PD deficient arm given DHA PP plus primaquine, and the G6PD normal arm receiving the same regimen


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Determine G6PD enzyme activity [ Time Frame: Day 0 ]
    Quantitative G6PD testing among all participants using the G6PD enzyme assay from Trinity Biologicals, USA, yielding G6PD enzyme results in U/g Hb.
  • Assess usefulness of field adapted WHO haemoglobin colour card vs. Hemocue [ Time Frame: Day 0 ]
    Comparison of quantitative (HemoCue, g/dL HB) and qualitative (WHO haemolglobin colour card) estimates of haemoglobin concentration
  • Assess usefulness of rapid test for G6PDd in predicting acute intravascular haemolysis [ Time Frame: Day 0 ]
    Comparison of rapid G6PD test (AccessBio, USA) qualitative result against quantitative G6PD assay to determine predictive value for clinically significant haemolysis
  • Proportion patients with ≥25% change in haemoglobin as a marker of intravascular haemolysis [ Time Frame: Change from Day 0 to Day 7 ]
    Comparing across all 4 arms: proportion of all patients with fractional change in haemoglobin ≥25% from day 0 to day 7
  • Plasma haemoglobin concentration as a marker of intravascular haemolysis [ Time Frame: Day 7 ]
    Comparing across all 4 arms: plasma haemoglobin concentration at day 7
  • Urine colour change as a marker of intravascular haemolysis [ Time Frame: Change from Day 0 to Day 7 ]
    Change in urine colour grade from day 0 to day 7 (Hillmen, Hall et al. 2004)
  • Fractional change in haemoglobin as a marker of intravascular haemolysis [ Time Frame: Change from Day 0 to Day 7 ]
    Comparing across all 4 arms: fractional change in haemoglobin on day 7 vs. day 0
  • Clearance rate of primaquine [ Time Frame: Day 0-7 ]
    Primaquine elimination clearance rate, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ
  • Half life of primaquine [ Time Frame: Day 0-7 ]
    Primaquine terminal elimination half life, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ
  • Primaquine volume of distribution [ Time Frame: Day 0-7 ]
    Primaquine apparent volume of distribution (Vd), modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ
  • Clearance rate of piperaquine [ Time Frame: Day 0-28 ]
    Piperaquine elimination clearance rate, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ
  • Half life of piperaquine [ Time Frame: Day 0-28 ]
    Piperaquine terminal elimination half life, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ
  • Piperaquine volume of distribution [ Time Frame: Day 0-28 ]
    Piperaquine apparent volume of distribution (Vd), modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ
  • Peak plasma concentration (Cmax) of primaquine [ Time Frame: Day 0-7 ]
    Cmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ
  • Peak plasma concentration (Cmax) of piperaquine [ Time Frame: Day 0-28 ]
    Cmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ
  • Time to primquine peak plasma concentration (Tmax) [ Time Frame: Day 0-7 ]
    Tmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ
  • Time to piperaquine peak plasma concentration (Tmax) [ Time Frame: Day 0-28 ]
    Tmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ
  • Area under the plasma concentration versus time curve - primaquine [ Time Frame: Day 0-7 ]
    Modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ
  • Area under the plasma concentration versus time curve - piperaquine [ Time Frame: Day 0-28 ]
    Modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ


Original Secondary Outcome: Same as current

Information By: Malaria Consortium

Dates:
Date Received: September 11, 2014
Date Started: October 2014
Date Completion:
Last Updated: August 22, 2016
Last Verified: August 2016