Vivax Malaria Clinical Trial
Official title:
A Study of the Pharmacokinetics of Primaquine in Lactating Women and Breastfed Infants for the Radical Treatment of Uncomplicated Maternal P. Vivax
Verified date | February 2016 |
Source | University of Oxford |
Contact | n/a |
Is FDA regulated | No |
Health authority | United Kingdom: Research Ethics Committee |
Study type | Interventional |
The weight of malaria falls most heavily on young children and pregnant women but studies of
the safety of antimalarials in pregnancy and lactation are few. The only recommended
medication used for radical treatment of P.vivax is primaquine. The 2010 WHO malaria
guidelines recommend its use in all patients with P.vivax infection in areas of low
transmission, in the absence of contraindications. Primaquine is contraindicated in
pregnancy. The postpartum period presents a key opportunity to definitively treat women who
suffer multiple malaria relapses during pregnancy. The 2010 WHO malaria treatment guidelines
allow for primaquine use during lactation but there are no studies to date quantifying
primaquine excretion in breast milk and the dose that breastfed infants would be exposed to
is unknown. The investigators propose to study the pharmacokinetics of primaquine in
maternal and infant plasma and in breast milk during a 14 day radical treatment of P.vivax.
Some inferences about the expected behavior of primaquine in lactation can be drawn from its
known pharmacologic properties. Primaquine pharmacokinetics have been well characterized in
healthy subjects and malaria patients after single and multiple oral dosing. Peak
concentrations are reached within 2-3 hours after dosing and the plasma elimination
half-life is ~7 hours. It is extensively distributed in the tissue and largely metabolized
to inert carboxyprimaquine, the major plasma metabolite, which undergoes further
biotransformation to unknown metabolites that are probably more toxic than the parent
compound. The identification of other metabolites in humans has been difficult to pursue
because the expected aminophenol metabolites are unstable.
No pharmacokinetic studies have been done to measure primaquine excretion in breast milk. A
few studies have been done of other antimalarials during lactation and have shown low levels
of drug in breast milk during treatment.
Status | Completed |
Enrollment | 20 |
Est. completion date | December 2014 |
Est. primary completion date | July 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Lactating women aged 18 years and older who are breast feeding one infant aged more than 28 days. - G6PD normal - History of proven P.vivax malaria that has not been treated with primaquine - Willingness and ability to comply with the study protocol for the duration of the trial - Written informed consent provided Exclusion Criteria: - Known hypersensitivity to primaquine, defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis - Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in mother - Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in infant - Pregnancy (urine test for HCG to be performed on any woman of child bearing age unless menstruating) - Blood smear positive for malaria at the time of enrolment - Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study - Hematocrit (HCT) <25% in the mother or <33% in the infant - Use of medications other than antipyretics in the past 7 days or Chloroquine in the past 2 months. - Use of primaquine since most recent malaria episode. |
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Thailand | Shoklo Malaria Research Unit | Mae Sot | Tak |
Lead Sponsor | Collaborator |
---|---|
University of Oxford |
Thailand,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Pharmacokinetic Parameters of Primaquine and Carboxyprimaquine in breast milk. Area Under Curve (AUC) | Primaquine and carboxyprimaquine pharmacokinetic parameters to day 13 in breast milk of lactating women treated with primaquine for radical treatment of P.vivax. | 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose | No |
Secondary | Pharmacokinetics Parameters of Primaquine and Carboxyprimaquine in blood. Area Under Curve (AUC). | Primaquine and carboxyprimaquine pharmacokinetic parameters to day 13 in the blood of lactating women and their breastfed infants | 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose | No |
Secondary | Concentration of Primaquine in saliva and urine. Area Under Curve (AUC). | Primaquine concentration in saliva and urine. | 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose | No |
Secondary | Primaquine dosage in infant - the relative infant dose. Area Under Curve (AUC). | Relative infant dose of Primaquine. | 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose | No |
Secondary | Assessment of adverse events during primaquine administration | Adverse events in mothers and infants during treatment. Number of Participants with Adverse Events as a Measure of Safety and Tolerability. | 63 days | Yes |
Secondary | Hematocrit levels in mother and child | Changes in maternal and infant hematocrit to day 63. | 63 days | Yes |
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