Phase 2 Efficacy Study of Primaquine and Methylene Blue

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 2

Conditions: Malaria

Treatments: Drug: Methylene blue; Drug: Amodiaquine; Drug: 0.25 mg/kg primaquine; Drug: Dihydroartemisinin-piperaquine; Drug: Sulphadoxine-pyrimethamine

Study type: Interventional

Funder types: Other

Identifiers

NCT02831023

UCSF CHR # 15-16839

Details and patient eligibility

About

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.

Full description

Protocol will be shared on request.

Enrollment: 80 patients

Sex: Male

Ages: 5 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

80 participants in 4 patient groups

SP-AQ only

Active Comparator group

Description:

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.

Treatment:

Drug: Sulphadoxine-pyrimethamine

Drug: Amodiaquine

SP-AQ plus PQ

Experimental group

Description:

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.

Treatment:

Drug: Sulphadoxine-pyrimethamine

Drug: Amodiaquine

Drug: 0.25 mg/kg primaquine

DP only

Active Comparator group

Description:

Participants in this arm will be treated with dihydroartemisinin-piperaquine (DP), which will be administered once a day for three days.

Treatment:

Drug: Dihydroartemisinin-piperaquine

DP plus MB

Experimental group

Description:

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).

Treatment:

Drug: Methylene blue