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

This study has been completed.
Sponsor:
Collaborator:
Wellcome Trust
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT01365598
First received: June 1, 2011
Last updated: June 11, 2013
Last verified: June 2013

June 1, 2011
June 11, 2013
December 2011
March 2013   (final data collection date for primary outcome measure)
  • Mean number of days to gametocyte clearance (gametocyte clearance time, GCT) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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.
  • Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up
  • Mean number of days to gametocyte clearance (gametocyte clearance time, GCT) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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).
  • Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up
Complete list of historical versions of study NCT01365598 on ClinicalTrials.gov Archive Site
  • Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    An estimate of the area under the curve of gametocytes (measured by QT-NASBA) seen over time, averaged per day of follow up (days 0-14) and interpolated from measured data points
  • Requirement for blood transfusion [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Percentage of children receiving blood transfusion per treatment arm during days 0-28
  • Follow-up day of Hb nadir [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)
  • Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Percentage (number) per treatment arm during days 0-28
  • Incidence of gastrointestinal symptoms after taking study drug [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]
    Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7
  • Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Total number of gametocytes (measured by QT-NASBA) seen over follow up, averaged per day of follow up (days 0-14)
  • Requirement for blood transfusion [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Percentage of children receiving blood transfusion per treatment arm during days 0-28
  • Follow-up day of Hb nadir [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)
  • Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Percentage (number) per treatment arm during days 0-28
  • Incidence of gastrointestinal symptoms after taking study drug [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]
    Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7
Not Provided
Not Provided
 
Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda
Evaluation of the Efficacy and Safety of Primaquine for Clearance of Gametocytes in Uncomplicated Falciparum Malaria in Uganda

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.

A single dose of 0.75mg/kg primaquine base is recommended by the WHO to block transmission of falciparum malaria from infected humans to mosquitoes by clearing gametocytes. However, the optimal dose for safety and efficacy has not been evaluated. Dose-finding data is important because primaquine has a dose-dependent risk of causing haemolysis (destruction of blood cells) in pre-disposed individuals, such as those with G6PD deficiency. G6PD deficiency is most prevalent in malaria-endemic areas. Therefore, it is essential that data on primaquine's safety is available in such areas.

The investigators hypothesise that lower doses of primaquine have a lower risk of adverse effects compared to the WHO-recommended dose, but retain the transmission-blocking efficacy.

The investigators propose to test this hypothesis in a four-arm clinical trial with a non-inferiority design to evaluate the efficacy and a superiority design to evaluate the safety of the WHO dose (0.75mg/kg) and lower doses of primaquine for clearance of P. falciparum gametocytes in children in Uganda. The study will include a pharmacokinetic analysis.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Falciparum Malaria
Drug: Primaquine
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).
Other Name: primaquine phosphate
  • Placebo Comparator: Placebo
    Non-active drug
    Intervention: Drug: Primaquine
  • Experimental: Low dose primaquine (PQ1)
    Lowest experimental dose of primaquine base: 0.1mg/kg
    Intervention: Drug: Primaquine
  • Experimental: Intermediate dose primaquine (PQ2)
    Intermediate experimental dose of primaquine base: 0.4mg/kg
    Intervention: Drug: Primaquine
  • Active Comparator: Reference dose primaquine (PQ-R)
    WHO-recommended dose of primaquine base: 0.75mg/kg
    Intervention: Drug: Primaquine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
468
May 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Both
1 Year to 10 Years
No
Contact information is only displayed when the study is recruiting subjects
Uganda
 
NCT01365598
PQPF912
Yes
London School of Hygiene and Tropical Medicine
London School of Hygiene and Tropical Medicine
Wellcome Trust
Principal Investigator: Alice C Eziefula, MBBS MCRP MRCPath London School of Hygiene and Tropical Medicine
London School of Hygiene and Tropical Medicine
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP