This study has been transitioned to CTIS with ID 2023-510232-36-00 check the CTIS register for the current data. to determine the concentration of currently often used ARV (doravirine, raltegravir, bictegravir, tenofovir alafenamide, emtricitabine)…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Area under the plasma and milk concentration curve are used to calculate milk
to plasma ratio.
Secondary outcome
The following pharmacokinetic parameters of ARV in plasma and/or
breastmilk will be described:
o AUC0-tau (AUC over a dosing interval) estimated using the rectangular method
(41).
o Peak plasma concentration (Cmax)
o Time to Cmax
o Concentration at end of dosing interval (Ctrough)
o Clearance
o Apparent volume of distribution
o Half life
o Parameter estimation trough compartmental modelling
Background summary
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.
Study objective
This study has been transitioned to CTIS with ID 2023-510232-36-00 check the CTIS register for the current data.
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.
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).
Study burden and risks
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 a better 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 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%), Steven Johnson syndrome
(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.
Side effects of RAL are comparable with those seen in bictegravir.
Gastro-intestinal (dyspepsia, abdominal pain, diarrhea), psychiatric
(depression, sleeping disturbances and abnormal dreams) and nervous system
effects (dizziness, vertigo) are noticed in 1-10% of users. On investigation
1-10% of the users of RAL have elevated liver enzymes or triglyceride levels.
Several cases of osteonecrosis and severe skin reactions (Steven Johnson
syndrome, toxic epidermal necrolysis etc) are reported.
Participation in this study requires subjects to be admitted during 24hours 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.
In subjects who chose to sustain from breastfeeding for a minimum of four days,
the risk of toxicity for their infants will be negligibly small. All study
drugs are metabolized by first line kinetics, which means that after 4-5 times
the elimination half-life of the drug, the plasma concentrations will be near
to zero. Because breastmilk concentrations are mainly determined by passive
diffusion from plasma, the breastmilk concentrations will most likely be lower
than the plasma concentrations. So, when a near to zero concentration in plasma
has been reached after 4-5 elimination half-life periods, the risk of getting
exposed to toxic concentrations via breastmilk will be nihil. Therefore,
subjects who agree to feed their infants in an alternative way (formula,
pre-pumped milk form before ingestion of study drug, donor milk etc) will have
to plan this alternative feeding in advance and might need to pump during this
period to retain milk-production. This might be conceived as an inconvenience.
Geert grooteplein zuid 10
Nijmegen 6525GA
NL
Geert grooteplein zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following 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 or
willing and able to sustain from breastfeeding during four days after ingestion
of study medication
• Able and willing to sign an informed consent
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• 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
Participation to other studies is not an exclusion criterion per se, when other
in- and exclusion criteria are met and the other study does not interfere with
the outcomes of the current study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-510232-36-00 |
| EudraCT | EUCTR2022-003715-29-NL |
| CCMO | NL83180.091.22 |