Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda

NCT01365598 | Completed Phase 3 DMC

• 1 other identifier: PQPF912
• Study Type: interventional
• Target: 468
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of lower doses of primaquine compared to the dose recommended by the WHO for reducing P. falciparum gametocytes in the infected human host to prevent transmission of falciparum malaria to the anopheles mosquito vector.

Conditions

Falciparum Malaria

Keywords

malaria; uncomplicated malaria; gametocytocidal drug; gametocytocidal; gametocyte; primaquine; transmission blocking; malaria transmission; sexual parasite; sexual stage; Uganda; Africa

Outcome Measures

Primary Outcomes (2)

• Mean number of days to gametocyte clearance (gametocyte clearance time, GCT)

  Mean number of days per treatment arm for gametocytes to become undetectable using sub-microscopic molecular testing methods (real-time nucleic acid sequence-based amplification, QT-NASBA)and interpolated from measured data points.

  14 days

• Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up

  Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up

  28 days

Secondary Outcomes (5)

• Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up

  14 days

• Requirement for blood transfusion

  28 days

• Follow-up day of Hb nadir

  28 days

• Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug

  28 days

• Incidence of gastrointestinal symptoms after taking study drug

  6 days

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Non-active drug

Drug: Primaquine

Low dose primaquine (PQ1)

EXPERIMENTAL

Lowest experimental dose of primaquine base: 0.1mg/kg

Drug: Primaquine

Intermediate dose primaquine (PQ2)

EXPERIMENTAL

Intermediate experimental dose of primaquine base: 0.4mg/kg

Drug: Primaquine

Reference dose primaquine (PQ-R)

ACTIVE COMPARATOR

WHO-recommended dose of primaquine base: 0.75mg/kg

Drug: Primaquine

Interventions

Primaquine DRUG

Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).

Also known as: primaquine phosphate

Intermediate dose primaquine (PQ2); Low dose primaquine (PQ1); Placebo; Reference dose primaquine (PQ-R)

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age \>/= 1 year and \</= 10 years
• Weight over 10kg
• Fever \>38 degrees C (tympanic) or history of fever in the last 24 hours
• P. falciparum parasitaemia \<500 000/µl
• Normal G6PD enzyme function

You may not qualify if:

• Enrolled in another study
• Evidence of severe illness/ danger signs
• Known allergy to study medications
• Haemoglobin \< 8g/dL)
• Started menstruation
• Pregnancy or breastfeeding
• Primaquine taken within the last 4 weeks
• Blood transfusion within the last 90 days
• Non-falciparum malaria co-infection

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Wellcome Trust: collaborator

Study Sites (1)

Walukuba Health Centre IV

Jinja, Eastern Region, Uganda

Location

Related Publications (7)

• Bousema T, Okell L, Shekalaghe S, Griffin JT, Omar S, Sawa P, Sutherland C, Sauerwein R, Ghani AC, Drakeley C. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar J. 2010 May 24;9:136. doi: 10.1186/1475-2875-9-136.

  PMID: 20497536 BACKGROUND

• Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, Enevold A, Alifrangis M, Mosha F, Sauerwein R, Bousema T. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS One. 2007 Oct 10;2(10):e1023. doi: 10.1371/journal.pone.0001023.

  PMID: 17925871 BACKGROUND

• Schneider P, Bousema JT, Gouagna LC, Otieno S, van de Vegte-Bolmer M, Omar SA, Sauerwein RW. Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. Am J Trop Med Hyg. 2007 Mar;76(3):470-4.

  PMID: 17360869 BACKGROUND

• Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010 May;54(5):1762-8. doi: 10.1128/AAC.01135-09. Epub 2010 Mar 1.

  PMID: 20194698 BACKGROUND

• Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo AP, Naing AL, Nyo MY, Myint NZ, Imwong M, Ashley E, Lee SJ, White NJ. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis. 2010 Oct;10(10):673-81. doi: 10.1016/S1473-3099(10)70187-0. Epub 2010 Sep 9.

  PMID: 20832366 BACKGROUND

• Chang HH, Meibalan E, Zelin J, Daniels R, Eziefula AC, Meyer EC, Tadesse F, Grignard L, Joice RC, Drakeley C, Wirth DF, Volkman SK, Buckee C, Bousema T, Marti M. Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda. Sci Rep. 2016 May 20;6:26330. doi: 10.1038/srep26330.

  PMID: 27197604 DERIVED

• Eziefula AC, Bousema T, Yeung S, Kamya M, Owaraganise A, Gabagaya G, Bradley J, Grignard L, Lanke KH, Wanzira H, Mpimbaza A, Nsobya S, White NJ, Webb EL, Staedke SG, Drakeley C. Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. Lancet Infect Dis. 2014 Feb;14(2):130-9. doi: 10.1016/S1473-3099(13)70268-8. Epub 2013 Nov 13.

  PMID: 24239324 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Primaquine

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

Study Officials

• Alice C Eziefula, MBBS MCRP MRCPath

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2011
• First Posted: June 3, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 12, 2013

Record last verified: 2013-06

Locations

UG (1)