- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02831023
Phase 2 Efficacy Study of Primaquine and Methylene Blue
January 9, 2017 updated by: University of California, San Francisco
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
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.
Study Overview
Status
Completed
Conditions
Detailed Description
Protocol will be shared on request.
Study Type
Interventional
Enrollment (Actual)
80
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Bamako, Mali
- Malaria Research and Training Centre
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
5 years to 50 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: SP-AQ only
Subjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days.
|
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine.
Doses will be administered by weight.
Other Names:
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.
|
Experimental: SP-AQ plus PQ
Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
|
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine.
Doses will be administered by weight.
Other Names:
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.
Primaquine will be administered in an aqueous solution according to weight-based dosing.
|
Active Comparator: DP only
Participants in this arm will be treated with dihydroartemisinin-piperaquine (DP), which will be administered once a day for three days.
|
160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets will be used to administer weight-based doses.
Other Names:
|
Experimental: DP plus MB
Study participants in this arm will receive DP as described above combined with once-daily methylene blue (MB) for 3 days, at 15 mg/kg/day (45 mg/kg total over 3 days).
|
Methylene blue will be given as minitablets in prepackaged sachets according to weight groups.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
7 day
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
42 days
|
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.
|
42 days
|
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.
|
42 days
|
Peak plasma concentration (Cmax) of primaquine
Time Frame: 24 hours
|
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
24 hours
|
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.
|
1 hour
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Roland Gosling, MD, PhD, University of California, San Francisco
- Principal Investigator: Alassane Dicko, MD, Malaria Research and Training Centre
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2016
Primary Completion (Actual)
January 1, 2017
Study Completion (Actual)
January 1, 2017
Study Registration Dates
First Submitted
July 6, 2016
First Submitted That Met QC Criteria
July 8, 2016
First Posted (Estimate)
July 13, 2016
Study Record Updates
Last Update Posted (Estimate)
January 11, 2017
Last Update Submitted That Met QC Criteria
January 9, 2017
Last Verified
January 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Folic Acid Antagonists
- Anti-Infective Agents, Urinary
- Renal Agents
- Primaquine
- Pyrimethamine
- Methylene Blue
- Piperaquine
- Sulfadoxine
- Fanasil, pyrimethamine drug combination
- Amodiaquine
- Artenimol
Other Study ID Numbers
- UCSF CHR # 15-16839
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Data can be shared on request
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on Sulphadoxine-pyrimethamine
-
London School of Hygiene and Tropical MedicineMinistry of Health, GhanaCompleted
-
London School of Hygiene and Tropical MedicineMalaria Research and Training Center, Bamako, Mali; Institut de Recherche en...CompletedMalaria | Respiratory InfectionsBurkina Faso, Mali
-
University of MelbourneUniversity of Barcelona; Papua New Guinea Institute of Medical Research; The... and other collaboratorsCompletedSexually Transmitted Infections | Malaria in Pregnancy | AnaemiaPapua New Guinea
-
Papua New Guinea Institute of Medical ResearchCase Western Reserve University; University of MelbourneCompletedAnemia | MalariaPapua New Guinea
-
London School of Hygiene and Tropical MedicineCompletedTrichomonas Vaginitis | Bacterial Vaginoses | Pregnancy MalariaZambia
-
University College Hospital, IbadanUnknown
-
London School of Hygiene and Tropical MedicineMinistry of Health, Uganda; DBL -Institute for Health Research and DevelopmentCompletedAnemia | Pregnancy | MalariaUganda
-
Ghana Health ServicesNetherlands Overseas AgencyCompleted
-
London School of Hygiene and Tropical MedicineTerminated
-
London School of Hygiene and Tropical MedicineKintampo Health Research Centre, GhanaNot yet recruitingMalaria | Schistosomiasis | Soil Transmitted Helminths | Seasonal Malaria Chemoprevention | Mass Drug Administration With Anthelminthic Drugs