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

NCT02364583 | Unknown Phase 4

• 1 other identifier: MRAC10.14
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasmodium Vivax

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability as measured by hemoglobin

  2 months post baseline

• Safety and tolerability as measured by methemoglobin

  2 months post baseline

• Safety and tolerability as measured by liver biochemistry

  2 months post baseline

• Safety and tolerability as measured by symptom questionnaire

  2 months post baseline

Secondary Outcomes (8)

• Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR)

  2 months from baseline

• Time to first or only clinical Plasmodium vivax episode

  2 months from baseline

• 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

• Pharmacokinetics - elimination half-life (t1/2)

  42 days

• Pharmacokinetics - clearance (CL)

  42 days

Study Arms (3)

14 day dose regimen

ACTIVE COMPARATOR

0.5 mg/kg oral Primaquine administered daily for 14 days

Drug: Primaquine

7 day dose regimen

ACTIVE COMPARATOR

1.0 mg/kg oral Primaquine administered daily for 7 days

Drug: Primaquine

3.5 day dose regimen

ACTIVE COMPARATOR

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

Drug: Primaquine

Interventions

Primaquine DRUG

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)

Also known as: Primaquine phosphate

14 day dose regimen; 3.5 day dose regimen; 7 day dose regimen

Eligibility Criteria

• Age: 5 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Papua New Guinea Institute of Medical Research: lead
• Walter and Eliza Hall Institute of Medical Research: collaborator
• The University of Western Australia: collaborator
• University of Oxford: collaborator
• Curtin University: collaborator

Study Sites (1)

PNG Institute of Medical Research

Madang, Madang Province, Papua New Guinea

RECRUITING

Related Publications (1)

• Moore BR, Salman S, Tobe R, Benjamin J, Yadi G, Kasian B, Laman M, Robinson LJ, Page-Sharp M, Betuela I, Batty KT, Manning L, Mueller I, Davis TME. Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children. Int J Infect Dis. 2023 Sep;134:114-122. doi: 10.1016/j.ijid.2023.05.063. Epub 2023 Jun 1.

  PMID: 37269941 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inoni Betuela, MD PhD

CONTACT

inoni.betuela@pngimr.org.pg

Ivo Mueller, PhD

CONTACT

+61393452555; ivomueller@fastmail.fm

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2014
• First Posted: February 18, 2015
• Study Start: June 1, 2010
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

PA (1)