NCT04984759: TBM

Tafenoquine and Primaquine in Colostrum and Breast Milk

Withdrawn Phase 4 Last updated 4 April 2024

What this trial tests

Phase 4 trial testing Primaquine in Healthy Lactating Women. Withdrawn.

Timeline

1 July 2023

Primary endpoint
30 June 2025

30 June 2025

Quick facts

Lead sponsor	University of Oxford
Phase	Phase 4
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Start date	1 July 2023
Primary completion	30 June 2025
Estimated completion	30 June 2025
Sites	1 location across Thailand

Drugs / interventions tested

• Primaquine — full drug profile →
• Tafenoquine (TAFENOQUINE) — full drug profile →

Conditions studied

• Healthy Lactating Women — all drugs for Healthy Lactating Women →

Sponsor

University of Oxford

Who can join

16 and older, female only, with Healthy Lactating Women. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Each year almost a million infants are born small for gestational age due to malaria infection in pregnancy. These infants are at risk for stillbirth or neonatal death, and being born too small predisposes the survivors to increased metabolic diseases later in life. Plasmodium vivax (PV) is the second most common malaria species globally. Its relapsing nature results in multiple episodes of PV in a single pregnancy, compounding growth restriction and stillbirth risk. Women with PV in one pregnancy may harbor dormant parasites (hypnozoites) in their liver the cause illness and poor fetal growth in a subsequent pregnancy.

Only radical cure with 8-aminoquinolines (8AQ)- primaquine (PMQ) or tafenoquine (TQ) - can eliminate hypnozoites, but these drugs are contraindicated in pregnancy. The postpartum period presents a key window of opportunity for giving radical cure to women of childbearing age with PV. Pharmacokinetic data is needed to support safe use of these drugs postpartum and World Health Organization has identified pharmacokinetic studies of 8AQ in lactation as a research priority.

Primaquine is excreted minimally in mature breast milk, at \<1% of the weight-adjusted relative infant dose (RID). As the main adverse event associated with both 8AQ - hemolysis glucose-6-phosphate dehydrogenase (G6PD) deficient individuals - is dose-dependent and negligible at low doses, this finding strongly supports its safe use in later lactation. This study is needed to determine if primaquine can also be given safely in the early postpartum period. There is no published data on tafenoquine excretion in breastmilk, and this study would quantify safety throughout early and late lactation.

Drug safety studies in lactation are essential to ensure medications are not denied and unnecessary interruption of breastfeeding is avoided. Demonstration of safety of radical cure for breastfeeding women in the postpartum period would allow women with PV in pregnancy and lactation to receive 8AQ after delivery, preventing illnesses in the postpartum period and subsequent pregnancies. Improved uptake of radical cure through elimination of unnecessary contraindications supports malaria elimination and community health.

The main purpose of this study is to characterize the transfer of tafenoquine and primaquine in breast milk of mothers receiving radical cure doses of 8AQ throughout the different phases of lactation - colostrum, transitional milk, and mature milk - in order to determine the degree of infant exposure.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Population pharmacokinetic modelling of primaquine exposures in lactating women and breastfed infants.
   Wattanakul T, Gilder ME, McGready R, Hanpithakpong W, et al · · 2024 · cited 6× · PMID 38719803 · DOI 10.1038/s41467-024-47908-y
2. Addressing health equity for breastfeeding women: primaquine for Plasmodium vivax radical cure.
   Abla N, Marrast AC, Jambert E, Richardson N, et al · · 2024 · cited 3× · PMID 39334094 · DOI 10.1186/s12936-024-05112-9