Plasmodium VivaxPhase 4NCT02364583
Investigation of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
A Phase 4 study testing Primaquine in people with Plasmodium Vivax, run by Papua New Guinea Institute of Medical Research at 1 site in Papua New Guinea.
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. Read more about this study
- Who is it for?
- Ages 5 to 10 years
- Conditions the study is for
- Plasmodium Vivax
- What is being tested?
- Primaquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 sitePapua New Guinea
- Study dates
- Jun 2010to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Inoni Betuela, MD PhD contact
Papua New Guinea1 site, 1 recruiting
- Recruiting
PNG Institute of Medical Research
Madang, Madang Province
Brioni R Moore, PhD, +61466266334, brioni.moore@uwa.edu.au
Inoni Betuela, MD PhD
About this study
Official title: Safety, Tolerability and Pilot Efficacy of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
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
- Being tested
- Primaquine
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrimaquineDrug
Also called Primaquine phosphate
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)
| Study group | Role | What they receive |
|---|---|---|
| 14 day dose regimen | Active comparator | 0.5 mg/kg oral Primaquine administered daily for 14 days Receives: Drug: Primaquine |
| 7 day dose regimen | Active comparator | 1.0 mg/kg oral Primaquine administered daily for 7 days Receives: Drug: Primaquine |
| 3.5 day dose regimen | Active comparator | 1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days Receives: Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as measured by hemoglobin
Measured: 2 months post baseline
Safety and tolerability as measured by methemoglobin
Measured: 2 months post baseline
Safety and tolerability as measured by liver biochemistry
Measured: 2 months post baseline
Safety and tolerability as measured by symptom questionnaire
Measured: 2 months post baseline
Secondary outcomes (8)
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.
Measured: 2 months from baseline
Time to first or only clinical Plasmodium vivax episode
Measured: 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
Measured: 2 months from baseline
Pharmacokinetics - elimination half-life (t1/2)
Measured: 42 days
Pharmacokinetics - clearance (CL)
Measured: 42 days
Pharmacokinetics - volume of distribution (Vd)
Measured: 42 days
Pharmacokinetics - maximal concentration (Cmax)
Measured: 42 days
Pharmacokinetics - area under the curve (AUC)
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2015 (estimated)
- Study startJun 2010
- Primary completionJun 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Plasmodium VivaxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Papua New Guinea Institute of Medical Research
- Sponsor type
- Other government
- Collaborators
- Walter and Eliza Hall Institute of Medical Research, The University of Western Australia, University of Oxford, Curtin University
- Responsible party
- Sponsor
- Investigators
- Inoni Betuela, MD, PhD, Principal investigator, PNG Institute of Medical ResearchIvo Mueller, PhD, Principal investigator, Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)J Kevin Baird, PhD, Principal investigator, Eijkman-Oxford Clinical Research Unit, Oxford UniversityTimothy ME Davis, FRAC, PhD, Principal investigator, The University of Western Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02364583
- Sponsor's protocol ID
- MRAC10.14
- Status last verified
- Oct 2015
- First submitted
- 13 Nov 2014
- Last updated
- 14 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 37269941
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability and Pilot Efficacy of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
- ClinicalTrials.gov ID
- NCT02364583
- Acronym / sponsor ID
- MRAC10.14
- Conditions
- Plasmodium Vivax
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Papua New Guinea Institute of Medical ResearchOther government
- Collaborators
- Walter and Eliza Hall Institute of Medical Research, The University of Western Australia, University of Oxford, Curtin University
- Study start
- Jun 2010
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 18 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 14 day dose regimen | Active comparator | Drug: Primaquine0.5 mg/kg oral Primaquine administered daily for 14 days |
| 7 day dose regimen | Active comparator | Drug: Primaquine1.0 mg/kg oral Primaquine administered daily for 7 days |
| 3.5 day dose regimen | Active comparator | Drug: Primaquine1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days |
Who may qualify
- Ages
- 5 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrimaquineAlso: Primaquine phosphatePrimaquine 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) | Drug | 14 day dose regimen, 3.5 day dose regimen, 7 day dose regimen |
Primary outcome
Safety and tolerability as measured by hemoglobin
Time frame: 2 months post baseline
Safety and tolerability as measured by methemoglobin
Time frame: 2 months post baseline
Safety and tolerability as measured by liver biochemistry
Time frame: 2 months post baseline
Safety and tolerability as measured by symptom questionnaire
Time frame: 2 months post baseline
8 secondary outcomes
Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR)
Time frame: 2 months from baseline
Time to first or only clinical Plasmodium vivax episode
Time frame: 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
Time frame: 2 months from baseline
Pharmacokinetics - elimination half-life (t1/2)
Time frame: 42 days
Pharmacokinetics - clearance (CL)
Time frame: 42 days
Pharmacokinetics - volume of distribution (Vd)
Time frame: 42 days
Pharmacokinetics - maximal concentration (Cmax)
Time frame: 42 days
Pharmacokinetics - area under the curve (AUC)
Time frame: 42 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.
- Derived from this study: PubMed 37269941Moore 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Inoni Betuela, MD PhD contact
Inoni Betuela, MD, PhD principal investigator
PNG Institute of Medical Research
Ivo Mueller, PhD principal investigator
Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)
J Kevin Baird, PhD principal investigator
Eijkman-Oxford Clinical Research Unit, Oxford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Primaquine in people with Plasmodium Vivax, run by Papua New Guinea Institute of Medical Research at 1 site in Papua New Guinea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Papua New Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Inoni Betuela, MD PhD (inoni.betuela@pngimr.org.pg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability as measured by hemoglobin (time frame: 2 months post baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02364583, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.