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Investigation of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection

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ClinicalTrials.gov Identifier: NCT02364583
Recruitment Status : Unknown
Verified October 2015 by Papua New Guinea Institute of Medical Research.
Recruitment status was:  Recruiting
First Posted : February 18, 2015
Last Update Posted : October 14, 2015
Sponsor:
Collaborators:
Walter and Eliza Hall Institute of Medical Research
The University of Western Australia
University of Oxford
Curtin University
Information provided by (Responsible Party):
Papua New Guinea Institute of Medical Research

Brief Summary:
This study specifically seeks to provide data on the safety, tolerability and pilot efficacy of short course, high dose primaquine treatment in Papua New Guinean children aged 5-10 years, in a cross-sectional study design. Community screened asymptomatic cases and/or cases of clinically diagnosed malaria admitted to the out-patient units of the health center, will be screened for Glucose-6-phosphate dehydrogenase deficiency (G6PD) and malaria illness by rapid diagnostic test and P. vivax infection confirmed by light microscopy. Following treatment with artemether-lumefantrine (Coartem), G6PD normal children will be enrolled into the study and followed for 2 months. Primaquine treatment will be allocated to study participants in a step-wise design; firstly receiving the current 14 day treatment regimen of 0.5 mg/kg total dose (n=40); secondly, a 7 day treatment regimen receiving a total dose of 1.0 mg/kg/day; then thirdly, receive 1.0 mg/kg twice daily dose (bd) for a total of 3.5 days, should the 7 day treatment prove to be safe and well tolerated. In addition to this dose-escalation study, the pharmacokinetic profiles of single doses of 0.5 mg/kg and 1.0 mg/kg will be determined using an intensive sampling protocol, in children aged 5-10 years. The pharmacokinetic profiles obtained by this sub-study will be essential for modeling the population pharmacokinetic data obtained from the dose-escalation study. As there is currently no data on the safety, tolerability and efficacy of primaquine in children, the present study will validate previous observation and contribute to the knowledge of primaquine as a treatment for liver stages of Plasmodium vivax infection.

Condition or disease Intervention/treatment Phase
Plasmodium Vivax Drug: Primaquine Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Tolerability and Pilot Efficacy of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
Study Start Date : June 2010
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: 14 day dose regimen
0.5 mg/kg oral Primaquine administered daily for 14 days
Drug: Primaquine
Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)
Other Name: Primaquine phosphate

Active Comparator: 7 day dose regimen
1.0 mg/kg oral Primaquine administered daily for 7 days
Drug: Primaquine
Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)
Other Name: Primaquine phosphate

Active Comparator: 3.5 day dose regimen
1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days
Drug: Primaquine
Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)
Other Name: Primaquine phosphate




Primary Outcome Measures :
  1. Safety and tolerability as measured by hemoglobin [ Time Frame: 2 months post baseline ]
  2. Safety and tolerability as measured by methemoglobin [ Time Frame: 2 months post baseline ]
  3. Safety and tolerability as measured by liver biochemistry [ Time Frame: 2 months post baseline ]
  4. Safety and tolerability as measured by symptom questionnaire [ Time Frame: 2 months post baseline ]

Secondary Outcome Measures :
  1. Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR) [ Time Frame: 2 months from baseline ]
    Thick and thin blood films, along with PCR samples, will be collected at time of recruitment and then at any time the participant develops fever within the study period.

  2. Time to first or only clinical Plasmodium vivax episode [ Time Frame: 2 months from baseline ]
  3. Comparison of the rate of incidence of P. vivax relapses in 3.5 or 7 day treatment arm compared to standard 14 day regimen [ Time Frame: 2 months from baseline ]
  4. Pharmacokinetics - elimination half-life (t1/2) [ Time Frame: 42 days ]
  5. Pharmacokinetics - clearance (CL) [ Time Frame: 42 days ]
  6. Pharmacokinetics - volume of distribution (Vd) [ Time Frame: 42 days ]
  7. Pharmacokinetics - maximal concentration (Cmax) [ Time Frame: 42 days ]
  8. Pharmacokinetics - area under the curve (AUC) [ Time Frame: 42 days ]


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Ages Eligible for Study:   5 Years to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Permanent resident in study area
  • Absence of history of hypersensitivity reactions to pre-treatment drugs
  • Positive for P. vivax infections on blood smear or PCR
  • Normal G6PD enzyme activity

Exclusion Criteria:

  • Features of severe malaria
  • Clinical evidence of nonmalarial illness
  • Severe malnutrition (weight for age nutritional Z score <60th percentile)
  • Moderate to severe anemia (Hb <8g/dL)
  • Permanent disability which prevents or impedes study participation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02364583


Contacts
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Contact: Inoni Betuela, MD PhD inoni.betuela@pngimr.org.pg
Contact: Ivo Mueller, PhD +61393452555 ivomueller@fastmail.fm

Locations
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Papua New Guinea
PNG Institute of Medical Research Recruiting
Madang, Madang Province, Papua New Guinea
Contact: Brioni R Moore, PhD    +61466266334    brioni.moore@uwa.edu.au   
Principal Investigator: Inoni Betuela, MD PhD         
Sponsors and Collaborators
Papua New Guinea Institute of Medical Research
Walter and Eliza Hall Institute of Medical Research
The University of Western Australia
University of Oxford
Curtin University
Investigators
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Principal Investigator: Inoni Betuela, MD, PhD PNG Institute of Medical Research
Principal Investigator: Ivo Mueller, PhD Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)
Principal Investigator: J Kevin Baird, PhD Eijkman-Oxford Clinical Research Unit, Oxford University
Principal Investigator: Timothy ME Davis, FRAC, PhD The University of Western Australia

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Responsible Party: Papua New Guinea Institute of Medical Research
ClinicalTrials.gov Identifier: NCT02364583     History of Changes
Other Study ID Numbers: MRAC10.14
First Posted: February 18, 2015    Key Record Dates
Last Update Posted: October 14, 2015
Last Verified: October 2015

Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Primaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents