Phase 2 Efficacy Study of Primaquine and Methylene Blue

Malaria Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02831023
• Other study ID #: UCSF CHR # 15-16839
• Status: Completed
• Phase: Phase 2
• First received: July 6, 2016
• Last updated: January 9, 2017
• Start date: July 2016
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mali: comités d'éthiqueUnited States: Institutional Review BoardUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Protocol will be shared on request.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 5 Years to 50 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Sulphadoxine-pyrimethamine
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.
• 0.25 mg/kg primaquine
Primaquine will be administered in an aqueous solution according to weight-based dosing.
• Dihydroartemisinin-piperaquine
160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets will be used to administer weight-based doses.
• Methylene blue
Methylene blue will be given as minitablets in prepackaged sachets according to weight groups.
• Amodiaquine
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.

Locations

Country	Name	City	State
Mali	Malaria Research and Training Centre	Bamako

Sponsors (6)

Lead Sponsor	Collaborator
University of California, San Francisco	Bill and Melinda Gates Foundation, Heidelberg University, London School of Hygiene and Tropical Medicine, Malaria Research and Training Center, Bamako, Mali, Radboud University

Country where clinical trial is conducted

Mali, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mosquito infectivity assessed through membrane feeding assays	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	No
Secondary	Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods.	Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.	42 days	No
Secondary	Asexual parasite prevalence and density	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	Yes
Secondary	Safety measurements including hemoglobin and signs of hemolysis	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	Yes
Secondary	Peak plasma concentration (Cmax) of primaquine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Area under the concentration curve (AUC) of primaquine.	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Elimination half life (t1/2) of primaquine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Peak plasma concentration (Cmax) of methylene blue	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Area under the concentration curve (AUC) of methylene blue	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Elimination half life (t1/2) of methylene blue	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Elimination half-life (t1/2) of sulphadoxine-pyrimethamine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Elimination half-life (t1/2) of dihydroartemisinin-piperaquine	Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.	24 hours	No
Secondary	Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms	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	No