Postpartum 8-aminoquinoline Breast Milk Study

Summary

In Papua New Guinea, administration of primaquine (PQ) or tafenoquine (TQ) to breastfeeding mothers is contraindicated during the first six months postpartum, when infants are recommended to be exclusively breastfed, because of a lack of comprehensive pharmacokinetic data on PQ/TQ neonatal and infant exposure via breast milk. The therapeutic restriction of PQ/TQ use in lactating women during the first six months postpartum effectively translates into \~10% of females being excluded from radical cure in endemic areas at any time. This is because many at risk women live in remote areas, are frequently lost to follow-up, or may have conceived again before they reattend. As a result, radical cure is rarely achieved and women are exposed to recurrent infections and cumulative risk of anaemia. Relapses may occur for years, placing subsequent pregnancies at risk and perpetuating intergenerational failure of fetal growth. They also contribute to malaria transmission, thus household and community exposure to vivax malaria.

The goal of the present study is to determine how much PQ/TQ is transferred to a suckling baby, if a mother receives a treatment course of PQ/TQ at time of delivery. We also want to confirm that this treatment is safe and has no major side effects for babies in Papua New Guinea.

The study Interventions areas follows: Group 1 - Participants receive PNG standard of care; PQ given 6-months postpartum; Group 2 - Participants receive a 14-day treatment regimen of PQ, at the standard dose prescribed in PNG for vivax radical cure (0.5 mg/kg/day for 14 days); Group 3 - Participants receive an accelerated high-dose 7-day treatment regimen of PQ, as per current WHO recommendations (1.0 mg/kg/day for 7 days); Group 4 - Participants receive a single dose of 300mg tafenoquine.

All participants will be monitored for a total duration of 6 months, with the safety, tolerability, pharmacokinetics and preliminary relapse efficacy of PQ/TQ evaluated at standardised time points over this period (Day 0, 1, 3, 6, 8, 15, 20, 28, and Month 2, 3, 4, 5 and 6). At each of these time points, participants will be asked to describe any symptoms they may be experiencing, participate in a medical examination, and provide a blood and breast milk sample for drug analysis and safety (biochemistry and haematology testing). The investigators will also collect a small blood sample (heel prick) from the infant to measure drug concentrations and safety testing.

Conditions

• Drug Pharmacokinetics in Healthy Volunteers

Interventions

DRUG

Daily primaquine (0.5 mg/kg per day) for 14 days given with food food and water

Women will receive daily doses of PQ (0.5 mg/kg per day) for 14 days at a total treatment dose of 7 mg/kg PQ. All doses will be to the nearest full tablet, with food and water to prevent gastrointestinal discomfort, as directly observed treatment. Women vomiting within 30 minutes of administration of any dose will be re-treated.

DRUG

Daily primaquine 1 mg/kg per day for 7 days given with food and water

Women will receive daily doses of PQ (1 mg/kg per day) for 7 days at a total treatment dose of 7 mg/kg PQ. All doses will be to the nearest full tablet, with food and water to prevent gastrointestinal discomfort, as directly observed treatment. Women vomiting within 30 minutes of administration of any dose will be re-treated.

DRUG

Single-dose tafenoquine given with food and water to prevent gastrointestinal discomfort

Women will receive a single dose of 300mg tafenoquine. Treatment will be given with food and water to prevent gastrointestinal discomfort, as directly observed treatment. Women vomiting within 30 minutes of administration of any dose will be re-treated.

Sponsors & Collaborators

• Menzies School of Health Research

  collaborator OTHER

• Papua New Guinea Institute of Medical Research

  collaborator OTHER_GOV

• Curtin University

  lead OTHER

Principal Investigators

• Brioni Moore, PhD · Curtin University

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-04-30

Primary Completion

2026-12-31

Completion

2027-05-31

Countries

• Papua New Guinea

Study Locations