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Completed

NCT Number: NCT02831023

Phase 2 Efficacy Study of Primaquine and Methylene Blue

The purpose of this study is to determine the most efficacious transmission blocking drug regimen for seasonal malaria chemoprophylaxis in Mali. The primary outcome measure will be the proportion of mosquitoes infected pre and post-treatment, assessed through membrane feeding and measured by oocyst prevalence in mosquitoes dissected on day 7 post feed. Primary endpoint will be a within group comparison between the mean of the pretreatment infectivity (Day 0) and infectivity at 7 days post first dose.

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Key information

Conditions

Malaria Infections Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

5 year–50 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Malaria Research and Training Centre

Bamako, Mali

About this study

Protocol will be shared on request.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Glucose-6-phosphate dehydrogenase (G6PD) normal defined by CareStart™ G6PD rapid diagnostic test (RDT) or the OSMMR2000 G6PD semi-qualitative test
  • Absence of symptomatic falciparum malaria, defined by fever upon enrollment
  • Presence of P. falciparum gametocytes on thick blood film at a density >30 gametocytes/µL (i.e. ≥2 gametocytes recorded in the thick film against 500 white blood cells)
  • No allergies to study drugs
  • No self-reported use of antimalarial drugs over the past 7 days (as reported by the participant)
  • Hemoglobin ≥ 10 g/dL
  • Individuals weighing <80 kg
  • No evidence of severe or chronic disease
  • Written, informed consent

Exclusion criteria

  • Age < 5 years or > 50 years
  • Female gender
  • Blood thick film negative for sexual stages of malaria
  • Previous reaction to study drugs/known allergy to study drugs
  • Signs of severe malaria, including hyperparasitemia, defined as asexual parasitemia > 100,000 parasites / µL)
  • Signs of acute or chronic illness, including hepatitis
  • Use of other medications (with the exception of paracetamol and/or aspirin)
  • Consent not given

Treatment and study plan

Sulphadoxine-pyrimethamine

Drug

Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.

Other names: Fansidar

0.25 mg/kg primaquine

Drug

Primaquine will be administered in an aqueous solution according to weight-based dosing.

Dihydroartemisinin-Piperaquine

Drug

160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets will be used to administer weight-based doses.

Other names: Eurartesim

Methylene Blue

Drug

Methylene blue will be given as minitablets in prepackaged sachets according to weight groups.

Amodiaquine

Drug

Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.

Primary outcomes

  1. Mosquito infectivity assessed through membrane feeding assays

    Time frame: 7 day

    Infectivity will be measured by oocyst prevalence in dissected mosquitoes. Primary endpoint will be a comparison between mean of pretreatment infectivity (day 0) and infectivity at days 2 and 7 post first dose.

Secondary outcomes

  1. Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods.

    Time frame: 42 days

    Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.

  2. Asexual parasite prevalence and density

    Time frame: 42 days

    Asexual parasitemia will be evaluated by blood smear microscopy and confirmed by more sensitive, molecular methods. Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.

  3. Safety measurements including hemoglobin and signs of hemolysis

    Time frame: 42 days

    The major safety endpoint is hemolysis. For this reason, hemoglobin and methemoglobin values will be measured before treatment, at baseline and on days 1, 2, 3, 7, 14, 28, and 42 post first dose. In addition, clinical review (including additional signs of hemolysis) will be assessed based on active and passive follow-up.

  4. Peak plasma concentration (Cmax) of primaquine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  5. Area under the concentration curve (AUC) of primaquine.

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  6. Elimination half life (t1/2) of primaquine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  7. Peak plasma concentration (Cmax) of methylene blue

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  8. Area under the concentration curve (AUC) of methylene blue

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  9. Elimination half life (t1/2) of methylene blue

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  10. Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  11. Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  12. Elimination half-life (t1/2) of sulphadoxine-pyrimethamine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  13. Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  14. Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  15. Elimination half-life (t1/2) of dihydroartemisinin-piperaquine

    Time frame: 24 hours

    Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

  16. Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms

    Time frame: 1 hour

    CYP2D6 and G6PD genotyping will be performed using Thermo Fisher Scientific OpenArray Technology and Copy Number Variation (CNV) assays on the QuantStudio™ 12K Flex Real-Time PCR System.

Sponsors and collaborators

Lead sponsor

University of California, San Francisco

Other

Collaborators

  • Bill and Melinda Gates Foundation
  • Heidelberg University
  • London School of Hygiene and Tropical Medicine
  • Malaria Research and Training Center, Bamako, Mali
  • Radboud University Medical Center

Registry information

Official study title

Efficacy, Safety, and Pharmacokinetics of Sulphadoxine-pyrimethamine-amodiaquine (SP-AQ), SP-AQ Plus Primaquine, Dihydroartemisinin-piperaquine (DP), DP Plus Methylene Blue for Preventing Transmission of P. Falciparum Gametocytes in Mali

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Jul 13, 2016
Registry last updated
Jan 11, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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