Clinical trial NCT02364583: Investigation of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
Official title: Safety, Tolerability and Pilot Efficacy of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Plasmodium Vivax
Lead sponsor: Papua New Guinea Institute of Medical Research
Sponsor class: OTHER_GOV
Collaborators: name: Walter and Eliza Hall Institute of Medical Research
name: The University of Western Australia
name: University of Oxford
name: Curtin University
First posted: 2015-02-18
Enrollment: 150
Sex: ALL
Minimum age (years): 5
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Safety and tolerability as measured by hemoglobin
timeFrame: 2 months post baseline
measure: Safety and tolerability as measured by methemoglobin
timeFrame: 2 months post baseline
measure: Safety and tolerability as measured by liver biochemistry
timeFrame: 2 months post baseline
measure: Safety and tolerability as measured by symptom questionnaire
timeFrame: 2 months post baseline
Secondary outcomes:
measure: Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR)
timeFrame: 2 months from baseline
measure: Time to first or only clinical Plasmodium vivax episode
timeFrame: 2 months from baseline
measure: Comparison of the rate of incidence of P. vivax relapses in 3.5 or 7 day treatment arm compared to standard 14 day regimen
timeFrame: 2 months from baseline
measure: Pharmacokinetics - elimination half-life (t1/2)
timeFrame: 42 days
measure: Pharmacokinetics - clearance (CL)
timeFrame: 42 days
measure: Pharmacokinetics - volume of distribution (Vd)
timeFrame: 42 days
measure: Pharmacokinetics - maximal concentration (Cmax)
timeFrame: 42 days
measure: Pharmacokinetics - area under the curve (AUC)
timeFrame: 42 days
Other outcomes:
Locations:
city: Madang
country: Papua New Guinea
facility: PNG Institute of Medical Research
state: Madang Province
Study officials:
affiliation: PNG Institute of Medical Research
name: Inoni Betuela, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)
name: Ivo Mueller, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eijkman-Oxford Clinical Research Unit, Oxford University
name: J Kevin Baird, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Western Australia
name: Timothy ME Davis, FRAC, PhD
role: PRINCIPAL_INVESTIGATOR
References: