Primaquine Pharmacokinetics in Lactating Women and Their Infants

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Oxford
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01780753
First received: October 8, 2012
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Vivax Malaria
Drug: Primaquine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of the Pharmacokinetics of Primaquine in Lactating Women and Breastfed Infants for the Radical Treatment of Uncomplicated Maternal P. Vivax

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Pharmacokinetic Parameters of Primaquine and Carboxyprimaquine in breast milk. Area Under Curve (AUC) [ Time Frame: 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose ] [ Designated as safety issue: No ]
    Primaquine and carboxyprimaquine pharmacokinetic parameters to day 13 in breast milk of lactating women treated with primaquine for radical treatment of P.vivax.


Secondary Outcome Measures:
  • Pharmacokinetics Parameters of Primaquine and Carboxyprimaquine in blood. Area Under Curve (AUC). [ Time Frame: 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose ] [ Designated as safety issue: No ]
    Primaquine and carboxyprimaquine pharmacokinetic parameters to day 13 in the blood of lactating women and their breastfed infants

  • Concentration of Primaquine in saliva and urine. Area Under Curve (AUC). [ Time Frame: 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose ] [ Designated as safety issue: No ]
    Primaquine concentration in saliva and urine.

  • Primaquine dosage in infant - the relative infant dose. Area Under Curve (AUC). [ Time Frame: 13 Days. Time Frame: predose, 0,1,2,3,4,6,8,12,24,72 hours; Day 7, Day 13 post-dose ] [ Designated as safety issue: No ]
    Relative infant dose of Primaquine.

  • Assessment of adverse events during primaquine administration [ Time Frame: 63 days ] [ Designated as safety issue: Yes ]
    Adverse events in mothers and infants during treatment. Number of Participants with Adverse Events as a Measure of Safety and Tolerability.

  • Hematocrit levels in mother and child [ Time Frame: 63 days ] [ Designated as safety issue: Yes ]
    Changes in maternal and infant hematocrit to day 63.


Estimated Enrollment: 24
Study Start Date: November 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primaquine
Primaquine GPO® (Government Pharmaceutical Organization, Thailand) 0.5 mg/kg will be given once daily for 14 days.
Drug: Primaquine
Primaquine GPO® (Government Pharmaceutical Organization, Thailand) 0.5 mg/kg will be given once daily for 14 days.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01780753

Contacts
Contact: Rose McGready, MD +66 (0) 55-545-021 rose@shoklo-unit.com
Contact: Mary E Gilder, MD +66 (0) 55-545-021 melliegilderjr@gmail.com

Locations
Thailand
Shoklo Malaria Research Unit Recruiting
Mae Sot, Tak, Thailand
Contact: Rose McGready, MD    +66 (0) 55-545-021    rose@shoklo-unit.com   
Contact: Mary E Gilder, MD    +66 (0) 55-545-021    melliegilderjr@gmail.com   
Principal Investigator: Mary E Gilder, MD         
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Rose McGready, MD University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01780753     History of Changes
Other Study ID Numbers: SMRU1203
Study First Received: October 8, 2012
Last Updated: August 27, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Primaquine
Vivax malaria
G6PD

Additional relevant MeSH terms:
Malaria
Malaria, Vivax
Protozoan Infections
Parasitic Diseases
Primaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014