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

Papua New Guinea Institute of Medical Research

Status and phase: Unknown; Phase 4

Conditions: Plasmodium Vivax

Treatments: Drug: Primaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT02364583

MRAC10.14

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 5 to 10 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 3 patient groups

14 day dose regimen

Active Comparator group

Description:

0.5 mg/kg oral Primaquine administered daily for 14 days

Treatment:

Drug: Primaquine

7 day dose regimen

Active Comparator group

Description:

1.0 mg/kg oral Primaquine administered daily for 7 days

Treatment:

Drug: Primaquine

3.5 day dose regimen

Active Comparator group

Description:

1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days

Treatment:

Drug: Primaquine