Safety and Tolerability of Low Dose Primaquine

Malaria, Falciparum Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02434952
• Other study ID #: 015NECHR
• Status: Completed
• Phase: Phase 4
• First received: September 11, 2014
• Last updated: August 22, 2016
• Start date: October 2014

Study information

• Verified date: August 2016
• Source: Malaria Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: Cambodia: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

Inclusion Criteria:

• Age = 1 year

• Presentation with a confirmed fever (= 38°C axilla or = 37.5°C aural) or history of fever in previous 48 hours +/- other clinical features of uncomplicated malaria

• Plasmodium falciparum monoinfection = 1 asexual form / 500 white blood cells

• Informed consent (written/verbal) provided by patient or relative/legal guardian

• Signed Assent form for children aged 12 to < 18 years

Exclusion Criteria:

• Clinical signs of severe malaria or danger signs

• Pregnant or breast feeding

• Unable or unwilling to take a pregnancy test (for women of child-bearing age)

• Women intending to become pregnant in the next 3 months

• Allergic to primaquine or DHA PP

• Patients taking drugs known to cause acute intravascular haemolytic anaemia (AIHA) in G6PD deficiency e.g. dapsone, nalidixic acid

• Patients on treatment for a significant illness e.g. HIV, tuberculosis (TB) treatment, steroids

• On drugs that could interfere with anti-malarial pharmacokinetics like antiretrovirals, cimetidine, ketoconazole, antiepileptic drugs, rifampicin

Study Design

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

Related Conditions & MeSH terms

• G6PD Deficiency
• Glucosephosphate Dehydrogenase Deficiency
• Malaria
• Malaria, Falciparum

Intervention

Drug:
• Dihydroartemisinin piperaquine (DHA PP)

• Primaquine

Locations

Country	Name	City	State
Cambodia	Ratanakiri Provincial Hospital	Ratanakiri

Sponsors (5)

Lead Sponsor	Collaborator
Malaria Consortium	Centers for Disease Control and Prevention, Institute Pasteur, Cambodia, National Centre for Parasitology, Entomology and Malaria Control, Cambodia, World Health Organization

Country where clinical trial is conducted

Cambodia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Haemoglobin concentration	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	Day 7	Yes
Secondary	Determine G6PD enzyme activity	Quantitative G6PD testing among all participants using the G6PD enzyme assay from Trinity Biologicals, USA, yielding G6PD enzyme results in U/g Hb.	Day 0	No
Secondary	Assess usefulness of field adapted WHO haemoglobin colour card vs. Hemocue	Comparison of quantitative (HemoCue, g/dL HB) and qualitative (WHO haemolglobin colour card) estimates of haemoglobin concentration	Day 0	No
Secondary	Assess usefulness of rapid test for G6PDd in predicting acute intravascular haemolysis	Comparison of rapid G6PD test (AccessBio, USA) qualitative result against quantitative G6PD assay to determine predictive value for clinically significant haemolysis	Day 0	No
Secondary	Proportion patients with =25% change in haemoglobin as a marker of intravascular haemolysis	Comparing across all 4 arms: proportion of all patients with fractional change in haemoglobin =25% from day 0 to day 7	Change from Day 0 to Day 7	Yes
Secondary	Plasma haemoglobin concentration as a marker of intravascular haemolysis	Comparing across all 4 arms: plasma haemoglobin concentration at day 7	Day 7	Yes
Secondary	Urine colour change as a marker of intravascular haemolysis	Change in urine colour grade from day 0 to day 7 (Hillmen, Hall et al. 2004)	Change from Day 0 to Day 7	Yes
Secondary	Fractional change in haemoglobin as a marker of intravascular haemolysis	Comparing across all 4 arms: fractional change in haemoglobin on day 7 vs. day 0	Change from Day 0 to Day 7	Yes
Secondary	Clearance rate of primaquine	Primaquine elimination clearance rate, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ	Day 0-7	No
Secondary	Half life of primaquine	Primaquine terminal elimination half life, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ	Day 0-7	No
Secondary	Primaquine volume of distribution	Primaquine apparent volume of distribution (Vd), modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ	Day 0-7	No
Secondary	Clearance rate of piperaquine	Piperaquine elimination clearance rate, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ	Day 0-28	No
Secondary	Half life of piperaquine	Piperaquine terminal elimination half life, modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ	Day 0-28	No
Secondary	Piperaquine volume of distribution	Piperaquine apparent volume of distribution (Vd), modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ	Day 0-28	No
Secondary	Peak plasma concentration (Cmax) of primaquine	Cmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ	Day 0-7	No
Secondary	Peak plasma concentration (Cmax) of piperaquine	Cmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ	Day 0-28	No
Secondary	Time to primquine peak plasma concentration (Tmax)	Tmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ	Day 0-7	No
Secondary	Time to piperaquine peak plasma concentration (Tmax)	Tmax taken directly from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ	Day 0-28	No
Secondary	Area under the plasma concentration versus time curve - primaquine	Modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP + PQ	Day 0-7	No
Secondary	Area under the plasma concentration versus time curve - piperaquine	Modelled from population pharmacokinetic data from all patients receiving at least one dose of DHA PP +/- PQ	Day 0-28	No

External Links

•   Malaria Consortium
•   National Centre for Parasitology, Entomology and Malaria Control Program, Cambodia