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

Primary Purpose

Plasmodium Vivax

Status

Unknown status

Phase

Phase 4

Locations

Papua New Guinea

Study Type

Interventional

Intervention

Primaquine

About this trial

This is an interventional treatment trial for Plasmodium Vivax

Eligibility Criteria

5 Years - 10 Years (Child)All SexesDoes not accept 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

Sites / Locations

PNG Institute of Medical ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

14 day dose regimen

7 day dose regimen

3.5 day dose regimen

Arm Description

0.5 mg/kg oral Primaquine administered daily for 14 days

1.0 mg/kg oral Primaquine administered daily for 7 days

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

Outcomes

Primary Outcome Measures

Safety and tolerability as measured by hemoglobin

Safety and tolerability as measured by methemoglobin

Safety and tolerability as measured by liver biochemistry

Safety and tolerability as measured by symptom questionnaire

Secondary Outcome Measures

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.

Time to first or only clinical Plasmodium vivax episode

Comparison of the rate of incidence of P. vivax relapses in 3.5 or 7 day treatment arm compared to standard 14 day regimen

Pharmacokinetics - elimination half-life (t1/2)

Pharmacokinetics - clearance (CL)

Pharmacokinetics - volume of distribution (Vd)

Pharmacokinetics - maximal concentration (Cmax)

Pharmacokinetics - area under the curve (AUC)

Full Information

NCT ID

NCT02364583

First Posted

November 13, 2014

Last Updated

October 12, 2015

Sponsor

Papua New Guinea Institute of Medical Research

Collaborators

Walter and Eliza Hall Institute of Medical Research, The University of Western Australia, University of Oxford, Curtin University

1. Study Identification

Unique Protocol Identification Number

NCT02364583

Brief Title

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

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Unknown status

Study Start Date

June 2010 (undefined)

Primary Completion Date

June 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Papua New Guinea Institute of Medical Research

Collaborators

Walter and Eliza Hall Institute of Medical Research, The University of Western Australia, University of Oxford, Curtin University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Plasmodium Vivax

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

14 day dose regimen

Arm Type

Active Comparator

Arm Description

0.5 mg/kg oral Primaquine administered daily for 14 days

Arm Title

7 day dose regimen

Arm Type

Active Comparator

Arm Description

1.0 mg/kg oral Primaquine administered daily for 7 days

Arm Title

3.5 day dose regimen

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Primaquine

Other Intervention Name(s)

Primaquine phosphate

Intervention Description

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)

Primary Outcome Measure Information:

Title

Safety and tolerability as measured by hemoglobin

Time Frame

2 months post baseline

Title

Safety and tolerability as measured by methemoglobin

Time Frame

2 months post baseline

Title

Safety and tolerability as measured by liver biochemistry

Time Frame

2 months post baseline

Title

Safety and tolerability as measured by symptom questionnaire

Time Frame

2 months post baseline

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

2 months from baseline

Title

Time to first or only clinical Plasmodium vivax episode

Time Frame

2 months from baseline

Title

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

Title

Pharmacokinetics - elimination half-life (t1/2)

Time Frame

42 days

Title

Pharmacokinetics - clearance (CL)

Time Frame

42 days

Title

Pharmacokinetics - volume of distribution (Vd)

Time Frame

42 days

Title

Pharmacokinetics - maximal concentration (Cmax)

Time Frame

42 days

Title

Pharmacokinetics - area under the curve (AUC)

Time Frame

42 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

10 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Inoni Betuela, MD PhD

inoni.betuela@pngimr.org.pg

First Name & Middle Initial & Last Name or Official Title & Degree

Ivo Mueller, PhD

Phone

+61393452555

ivomueller@fastmail.fm

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Inoni Betuela, MD, PhD

Organizational Affiliation

PNG Institute of Medical Research

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ivo Mueller, PhD

Organizational Affiliation

Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

J Kevin Baird, PhD

Organizational Affiliation

Eijkman-Oxford Clinical Research Unit, Oxford University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Timothy ME Davis, FRAC, PhD

Organizational Affiliation

The University of Western Australia

Official's Role

Principal Investigator

Facility Information:

Facility Name

PNG Institute of Medical Research

City

Madang

State/Province

Madang Province

Country

Papua New Guinea

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Brioni R Moore, PhD

Phone

+61466266334

brioni.moore@uwa.edu.au

First Name & Middle Initial & Last Name & Degree

Inoni Betuela, MD PhD

12. IPD Sharing Statement

Learn more about this trial

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

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