Study on PhArmacokinetics of First liNe Antiretrovirals in Healthy Breastfeeding Volunteers (PANNA-B PK)

No to little data exists on penetration of antiretroviral drugs in breastmilk. Too high concentrations may lead to infant toxicity and too low concentrations may lead to development of resistance in case the infant inadvertently becomes infected with the virus.

The aim of this trial is to determine the concentration of currently often used ARV (doravirine, raltegravir, bictegravir, tenofovir alafenamide, emtricitabine) in breast milk after administration of a single dose Study design: This is a single centre, single dose, open label, pharmacokinetic study in healthy volunteers.

Study population: Adult, healthy volunteers at the end of their breastfeeding period Intervention: Administration of one dose of either doravirine (DOR) 100mg, raltegravir (RAL) 1200mg or a combination of tenofovir alafenamide 25mg, emtricitabine 200mg and bictegravir 50mg (BIC/FTC/TAF).

Main study parameters/endpoints: Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio.

Study Overview

• Status: Completed
• Conditions: Hiv
• Intervention / Treatment: Drug: Doravirine 100Mg Tab; Drug: Biktarvy 50/200/25 Tab

Detailed Description

Rationale: Although current guidelines advise against breastfeeding while using antiretrovirals in people living with HIV, some women choose to breastfeed because advantages of breastfeeding may exceed the possible risk of HIV transmission to the newborn. However, no sound recommendation can be made on which antiretrovirals are most suitable during breastfeeding, because no to little data on penetration of these drugs in breastmilk exist. Too high concentrations may lead to infant toxicity and too low concentrations may lead to development of resistance in case the infant inadvertently becomes infected with the virus.

Objective: to determine the concentration of currently often used ARV (doravirine, raltegravir, bictegravir, tenofovir alafenamide, emtricitabine) in breast milk after administration of a single dose Study design: This is a single centre, single dose, open label, pharmacokinetic study in healthy volunteers.

Study population: Adult, healthy volunteers at the end of their breastfeeding period Intervention: Administration of one dose of either doravirine (DOR) 100mg, raltegravir (RAL) 1200mg or a combination of tenofovir alafenamide 25mg, emtricitabine 200mg and bictegravir 50mg (BIC/FTC/TAF).

Main study parameters/endpoints: Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects will not directly benefit from this study, but will contribute to knowledge on breastmilk transfer of ARV and possibly enable people living with HIV to make an informed decision on breastfeeding while using these medications.

No harm is expected from participation in this study, but possible side effects should be anticipated. Known side effects of DOR are nausea (4%) and headache (3%), abnormal dreams and insomnia (1-10%), dizziness and somnolence and fatigue (1-10%). BIC/FTC/TAFs and RALs known side effects are: headache (5%), diarrhoea (5%) and nausea (4%), depression and abnormal dreams and fatigue (1-10%), suicidal ideation (0,1-1%), angio-edema (0,1-1%) and Steven Johnson syndrome (0,01-0,1%) and osteonecrosis (0,01-0,1%). Due to the fact that only one dose of the drugs will be ingested, the risk of development of one or more of these side effects is considered to be low.

Participation in this study requires subjects to be admitted for 12 hours, a visit the next morning and a return visit 7 days later. During the sampling day an intravenous indwelling catheter is installed for collection of blood samples. A total volume of 25-50ml of blood, 2 urine samples and 6 breastmilk samples (expressed using a personal electronic pump) are collected. No harm is to be expected from these sample collection procedures.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• At least 18 years of age at the moment of screening
• At least 10 days post partum
• At the end of breastfeeding period; subject is able to produce breastmilk at least two times a day and is no longer feeding infant at start of study
• Able and willing to sign an informed consent

Exclusion Criteria:

• Relevant co-medication or comorbidity that might interfere with drug absorption, distribution, metabolism or excretion
• Inability to take drugs according to the instructions (i.e. with food)
• Presence of positive HIV screening or HIV RNA
• Presence of HBsAg or HBcAg without anti-HBs
• Presence of grade III/IV anaemia (i.e. Hb <4.6 mmol/L or <7.4 g/dL).
• Presence of hereditary forms of severe galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doravirine; 1 single dose of 100mg doravirine taken orally	Drug: Doravirine 100Mg Tab; 1 single dose of 100mg taken orally; Other Names: pifeltro
Experimental: Biktarvy; 1 single dose of 25/200/50mg taken orally	Drug: Biktarvy 50/200/25 Tab; 1 single dose of 50/200/25 taken orally; Other Names: biktarvy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
M:P Ratio	Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio	24hours after ingestion of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCtau	AUC over dosing interval	24hours after ingestion of study drug
Cmax	Peak plasma concentration	Within 24 hours after ingestion of study drug
Ctrough	Concentration at the end of dosing interval	24hours after ingestion of study drug
Clearance of Study Drugs	Clearance of the study drugs	24hours after ingestion of study drug
Apparent Volume of Distribution	Apparent volume of distribution of study drug	24hours after ingestion of study drug
Half Life	Half life of study drug	24hours after ingestion of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant Dose	Concentrations in breastmilk will be extrapolated to infant dosages	24hours after ingestion of study drug

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Merck Sharp & Dohme LLC; ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Angela Colbers, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): November 1, 2024
• Study Completion (Actual): April 28, 2025

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; doravirine; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: PANNA-B PK

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No