Postpartum 8-aminoquinoline Breast Milk Study

NCT07060404 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RES68007
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

primaquine; tafenoquine; vivax malaria; pharmacokinetics; postpartum; lactation; infant exposure

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic: Distribution half -life

  Pharmacokinetic parameters of primaquine (PQ) (and primary metabolite carboxyprimaquine) and tafenoquine (TQ) in breast milk (colostrom and transitional milk) to determine relative infant exposure. Based on drug concentrations determined from venous blood samples (mothers) and heel prick samples (infants) collected at baseline (Day 0) 1, 3, 6, 8,15, 20 and 28 (and 56 for Group 4).

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ)

• Pharmacokinetic: Termination elimination half-life

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ).

• Pharmacokinetic: Absorption half-life

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ).

• Pharmacokinetics: Clearance

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ).

• Pharmacokinetics: Volume of distribution

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ).

• Pharmacokinetics: Maximal concentration

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ).

• Pharmacokinetics: Area under concentration-time curve

  Group 2 and 3: 28 days after first drug dose (PQ) and Group 4: 56 days after drug administration (TQ).

Secondary Outcomes (9)

• Safety: Change in haemoglobin over 28 days

  Up to 28 days

• Safety: Change in haemotocrit over 28 days

  Up to 28 days

• Safety: Change in methaemoglobin over 28 days

  Up to 28 days

• Safety: Change in maternal and infant weight in kilograms over 28 days

  Up to 28 days

• Safety: Frequency of self-reported adverse events

  Up to 7 days after completion of treatment regimen

Study Arms (4)

Group1 - control

NO INTERVENTION

Participants will receive no intervention at time of delivery. As per standard care in PNG, each participant will receive primaquine at 6-months postpartum (completion of study procedures).

Group 2 - PQ14

EXPERIMENTAL

Daily oral primaquine as 0.5 mg/kg per day for 14 days, taken with food and water

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

Group 3 - PQ7

EXPERIMENTAL

Daily oral primaquine 1 mg/kg per day for 7 days, taken with food and water

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

Group 4 - TQ

EXPERIMENTAL

Single dose tafenoquine as 300mg taken with food and water

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

Interventions

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

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.

Also known as: Primacin, Primaquine phosphate

Group 3 - PQ7

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

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.

Also known as: Tafenoquine succinate, Kodatef

Group 4 - TQ

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

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.

Also known as: Primacin, Primaquine phosphate

Group 2 - PQ14

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Females as required to be lactating postpartum women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age
• Both mother and infant have G6PD activity \>70% (normal activity; SD Biosensor)
• They have no significant co-morbidity
• Delivered a live singleton baby within past 48-hours
• Rapid diagnostic test negative for malaria
• No history of hypersensitivity to 8-aminoquinoline drugs
• Plan to exclusively breastfeed for at least two months
• History of vivax malaria (as per health book)
• They can attend follow-up assessments for the duration of the study

You may not qualify if:

• Either mother/infant have G6PD activity \<70% (SD Biosensor)
• Either mother/infant have significant co-morbidity
• Mother did not deliver a live singleton within past 48-hours
• Mother/infant are rapid diagnostic test positive for malaria
• Mother has a history of hypersensitivity to 8-aminoquinoline drugs
• Mother does not plan to exclusively breastfeed for at least two months
• Mother does not have a history of vivax malaria (as per health book)
• Cannot or are not willing to attend follow-up assessments for the duration of the study

Sponsors & Collaborators

• Curtin University: lead
• Menzies School of Health Research: collaborator
• Papua New Guinea Institute of Medical Research: collaborator

Study Sites (1)

Alexishafen Health Centre

Madang, Madang Province, MP511, Papua New Guinea

Location

MeSH Terms

Conditions

Malaria, Vivax; Breast Feeding

Interventions

Food; Water; Primaquine; tafenoquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Brioni Moore, PhD

  Curtin University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brioni Moore, PhD

CONTACT

+61 8 9266 2956; brioni.moore@curtin.edu.au

Paula Tesine, MD

CONTACT

+675 434 0208; paula.tesine@pngimr.org.pg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: July 11, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 18, 2026

Record last verified: 2025-07

Locations

PA (1)