Phase 2 Efficacy Study of Primaquine and Methylene Blue

NCT02831023 | Completed Phase 2 DMC

• 1 other identifier: UCSF CHR # 15-16839
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (16)

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

  42 days

• Asexual parasite prevalence and density

  42 days

• Safety measurements including hemoglobin and signs of hemolysis

  42 days

• Peak plasma concentration (Cmax) of primaquine

  24 hours

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

  24 hours

Study Arms (4)

SP-AQ only

ACTIVE COMPARATOR

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.

Drug: Sulphadoxine-pyrimethamine; Drug: Amodiaquine

SP-AQ plus PQ

EXPERIMENTAL

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.

Drug: Sulphadoxine-pyrimethamine; Drug: 0.25 mg/kg primaquine; Drug: Amodiaquine

DP only

ACTIVE COMPARATOR

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

Drug: Dihydroartemisinin-piperaquine

DP plus MB

EXPERIMENTAL

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).

Drug: Methylene blue

Interventions

Sulphadoxine-pyrimethamine DRUG

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

Also known as: Fansidar

SP-AQ only; SP-AQ plus PQ

0.25 mg/kg primaquine DRUG

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

SP-AQ plus PQ

Dihydroartemisinin-piperaquine DRUG

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

Also known as: Eurartesim

DP only

Methylene blue DRUG

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

DP plus MB

Amodiaquine DRUG

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

SP-AQ only; SP-AQ plus PQ

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Malaria Research and Training Center, Bamako, Mali: collaborator
• Radboud University Medical Center: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Heidelberg University: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Malaria Research and Training Centre

Bamako, Mali

Location

Related Publications (1)

• Dicko A, Roh ME, Diawara H, Mahamar A, Soumare HM, Lanke K, Bradley J, Sanogo K, Kone DT, Diarra K, Keita S, Issiaka D, Traore SF, McCulloch C, Stone WJR, Hwang J, Muller O, Brown JM, Srinivasan V, Drakeley C, Gosling R, Chen I, Bousema T. Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial. Lancet Infect Dis. 2018 Jun;18(6):627-639. doi: 10.1016/S1473-3099(18)30044-6. Epub 2018 Feb 6.

  PMID: 29422384 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination; Primaquine; Methylene Blue; Amodiaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring

Study Officials

• Roland Gosling, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Alassane Dicko, MD

  Malaria Research and Training Centre

  PRINCIPAL INVESTIGATOR

• Teun Bousema, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 13, 2016
• Study Start: July 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 11, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share

Locations

MA (1)