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

Plasmodium Vivax Clinical Trial

Official title:

Safety, Tolerability and Pilot Efficacy of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02364583
• Other study ID #: MRAC10.14
• Status: Recruiting
• Phase: Phase 4
• First received: November 13, 2014
• Last updated: October 12, 2015
• Start date: June 2010
• Est. completion date: December 2016

Study information

• Verified date: October 2015
• Source: Papua New Guinea Institute of Medical Research
• Contact: Inoni Betuela, MD PhD
• Email: inoni.betuela[@]pngimr.org.pg
• Is FDA regulated: No
• Health authority: Papua New Guinea: PNG Medical Research Advisory Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 10 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Plasmodium Vivax

Intervention

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)

Locations

Country	Name	City	State
Papua New Guinea	PNG Institute of Medical Research	Madang	Madang Province

Sponsors (5)

Lead Sponsor	Collaborator
Papua New Guinea Institute of Medical Research	Curtin University of Technology, The University of Western Australia, University of Oxford, Walter and Eliza Hall Institute of Medical Research

Country where clinical trial is conducted

Papua New Guinea, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as measured by hemoglobin		2 months post baseline	No
Primary	Safety and tolerability as measured by methemoglobin		2 months post baseline	Yes
Primary	Safety and tolerability as measured by liver biochemistry		2 months post baseline	Yes
Primary	Safety and tolerability as measured by symptom questionnaire		2 months post baseline	No
Secondary	Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR)	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 months from baseline	No
Secondary	Time to first or only clinical Plasmodium vivax episode		2 months from baseline	No
Secondary	Comparison of the rate of incidence of P. vivax relapses in 3.5 or 7 day treatment arm compared to standard 14 day regimen		2 months from baseline	No
Secondary	Pharmacokinetics - elimination half-life (t1/2)		42 days	No
Secondary	Pharmacokinetics - clearance (CL)		42 days	No
Secondary	Pharmacokinetics - volume of distribution (Vd)		42 days	No
Secondary	Pharmacokinetics - maximal concentration (Cmax)		42 days	No
Secondary	Pharmacokinetics - area under the curve (AUC)		42 days	No