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MalariaPhase 2NCT02831023

Phase 2 Efficacy Study of Primaquine and Methylene Blue

A Phase 2 study testing Sulphadoxine-pyrimethamine, 0.25 mg/kg primaquine and Dihydroartemisinin-piperaquine in people with Malaria, run by University of California, San Francisco at 1 site in Mali.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 5 to 50 years, men onlyHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
Sulphadoxine-pyrimethamine, 0.25 mg/kg primaquine and Dihydroartemisinin-piperaquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteMali
Study dates
Jul 2016to Jan 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 50 years
  • Men only
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • 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
Show all 9Show fewer
  • Individuals weighing <80 kg
  • No evidence of severe or chronic disease
  • Written, informed consent

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

Mali1 site

  • Malaria Research and Training Centre

    Bamako

Other trials in Mali

About this study

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

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.

Read the detailed description

Protocol will be shared on request.

Conditions
Malaria
Being tested
Sulphadoxine-pyrimethamine, 0.25 mg/kg primaquine, Dihydroartemisinin-piperaquine, Methylene blue, Amodiaquine
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sulphadoxine-pyrimethamineDrug

    Also called Fansidar

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

  • 0.25 mg/kg primaquineDrug

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

  • Dihydroartemisinin-piperaquineDrug

    Also called Eurartesim

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

  • Methylene blueDrug

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

  • AmodiaquineDrug

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

Study groups in NCT02831023
Study groupRoleWhat they receive
SP-AQ onlyActive comparatorSubjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days.
Receives: Drug: Sulphadoxine-pyrimethamine; Drug: Amodiaquine
SP-AQ plus PQExperimentalParticipants 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.
Receives: Drug: Sulphadoxine-pyrimethamine; Drug: 0.25 mg/kg primaquine; Drug: Amodiaquine
DP onlyActive comparatorParticipants in this arm will be treated with dihydroartemisinin-piperaquine (DP), which will be administered once a day for three days.
Receives: Drug: Dihydroartemisinin-piperaquine
DP plus MBExperimentalStudy 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).
Receives: Drug: Methylene blue

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 7 day

Secondary outcomes (16)

  1. 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.

    Measured: 42 days

  2. 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.

    Measured: 42 days

  3. 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.

    Measured: 42 days

  4. Peak plasma concentration (Cmax) of primaquine

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

  7. Peak plasma concentration (Cmax) of methylene blue

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

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

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

    Measured: 24 hours

  16. 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.

    Measured: 1 hour

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionJan 2017
  4. Study completionJan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02831023
Sponsor's protocol ID
UCSF CHR # 15-16839
Status last verified
Jan 2017
First submitted
6 Jul 2016
Last updated
11 Jan 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Data can be shared on request

Publications

  • 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.

    PubMed 29422384

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sulphadoxine-pyrimethamine, 0.25 mg/kg primaquine and Dihydroartemisinin-piperaquine in people with Malaria, run by University of California, San Francisco at 1 site in Mali.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mosquito infectivity assessed through membrane feeding assays (time frame: 7 day). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02831023, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2017.

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