In this study we will look at how quickly and to what extent the study compound MEN1611 is absorbed, transported, and eliminated from the body (this is called pharmacokinetics) and how this is influenced by the approved drug itraconazole fluvoxamine…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Cancer with PIK3CA mutation
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the effect of CYP3A4/P-gp (itraconazole) or CYP1A2/3A4
(fluvoxamine) inhibition on the PK of MEN1611 single-dose in healthy subjects.
Secondary outcome
- To evaluate the effect on the electrocardiographic parameters in healthy
subjects of MEN1611 single-dose alone and in presence of a CYP3A4/P-gp
inhibitor (itraconazole) or a CYP1A2/3A4 inhibitor (fluvoxamine).
- To assess the safety and tolerability of MEN1611 in healthy volunteers when
co-administered with a CYP3A4/P-gp inhibitor (itraconazole) or with a
CYP1A2/3A4 inhibitor (fluvoxamine).
Background summary
MEN1611 is a new compound that may potentially be used for the treatment of
cancer. MEN1611 intervenes in a mechanism called PI3K/AKT. PI3K/AKT plays an
important role in cell growth and cell death. Its abnormal activation can cause
tumor cells to proliferate quickly. MEN1611 inhibits PI3K/AKT and thereby aims
to inhibit tumor growth.
Study objective
In this study we will look at how quickly and to what extent the study compound
MEN1611 is absorbed, transported, and eliminated from the body (this is called
pharmacokinetics) and how this is influenced by the approved drug itraconazole
fluvoxamine. Drugs are broken down in the liver by specific enzymes.
Itraconazole Fluvoxamine can inhibit these enzymes. We will investigate whether
this results in changed levels of the study compound MEN1611 in your blood.
We also investigate how safe the study compound MEN1611 is and how well it is
tolerated when it is used by healthy participants. We do this both when MEN1611
is given alone and when it given in combination with itraconazole fluvoxamine.
MEN1611 has been used by humans before. In addition, it has been extensively
tested in the laboratory and on animals.
Itraconazole is an approved drug that is used for the treatment of infections
caused by fungus. In this study it is used because it decreases the activity of
a liver enzyme that is important for the breakdown of drugs in the body. We
will investigate if itraconazole influences the way the body handles MEN1611.
Fluvoxamine is an approved drug that is used for the treatment of depression
and obsessive compulsive disorder (OCD). In this study it is used because it
decreases the activity of a liver enzyme that is important for the breakdown of
drugs in the body. We will investigate if fluvoxamine influences the way the
body handles MEN1611.
Study design
For the Itraconazole group:
- Screening visit: On a day between Day -23 and Day -3
- Arrival: Day -2
- In-house stay: Day -2 until Day 15
- Departure: Day 15
- Follow-up visit: On a day between Day 28 and Day 33
For the Fluvoxamine group:
- Screening visit: On a day between Day -23 and Day -3
- Arrival: Day -2
- In-house stay: Day -2 until Day 13
- Departure: Day 13
- Follow-up visit: On a day between Day 26 and Day 31
The volunteer will receive MEN1611 as oral capsules with 240 milliliters (mL)
of water.
They have to remain sitting or in a half-lying position for the first 4 hours
after MEN1611 dosing (except when instructed otherwise by one of the
investigators).
Itraconazole will be given as an oral solution of 20 mL.
Fluvoxamine will be given as an oral tablet with 240 mL of water.
Intervention
In total the volunteer will receive 2 doses of MEN1611.
Each dose will be 48 mg and will be given as 3 capsules of 16 mg each.
Itraconazole group will receive MEN1611 on Day 1 and on Day 12.
Fluvoxamine group will receive MEN1611 on Day 1 and on Day 10.
For the Itraconazole group: Itraconazole will be given once daily from Day 4 to
Day 14, so in total 11 times.
Each dose will be 200 mg and will be given as a drink.
For the Fluvoxamine group: Fluvoxamine will be given once daily from Day 4 to
Day 12, so in total 9 times.
Each dose will be 50 mg and will be given as a single tablet.
Study burden and risks
Blood draw:
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula can sometimes lead to inflammation, swelling, hardening of the vein,
blood clotting, and bleeding in the environment of the puncture site. In some
individuals, a blood draw can sometimes cause pallor, nausea, sweating, low
heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take about 171,5 mL (Itraconazole group) or 169,5 mL
(Fluvoxamine group) of blood from screening to follow-up. This amount does not
cause any problems in adults. To compare: a blood donation involves 500 mL of
blood being taken at once each time. If the investigator thinks it is necessary
for the safety of a participant, extra samples might be taken for possible
additional testing. If this happens, the total amount of blood drawn may be
more than the amount indicated above.
Heart tracing:
To make a heart tracing, electrodes will be placed on arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
Meals/Fasting:
If someone has to fast for a prolonged time during the study, this may lead to
symptoms such as dizziness, headache, stomach upset, or fainting.
Coronavirus test:
Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause gagging. When the sample is taken from the back of the
nose, The volunteer may experience a stinging sensation and eyes may become
watery.
Via Sette Santi 1
Firenze 50131
IT
Via Sette Santi 1
Firenze 50131
IT
Listed location countries
Age
Inclusion criteria
1. Be able to understand the study procedures and agree to participate in the
study by giving written informed consent prior to any Study related activity
(including screening) is performed.
2. Healthy males and healthy sterile or postmenopausal females aged 18 to 65
years.
3. BMI between >=18.5 kg/m2 and <30 kg/m2 with a body weight >50 kg.
4. Considered by the Investigator to be in good health as judged for
participation in this study as determined during the medical history review,
physical examination, vital signs, ECG and clinical laboratory.
5. Haematology and biochemistry without clinically significant abnormalities at
Screening. NOTE: ALT, AST, GGT, fasting glucose and glycosylated haemoglobin
(HbA1c) must be within the Upper Limit of Normal (ULN).
Exclusion criteria
1. Females of childbearing potential, pregnant or breastfeeding.
2. Females postmenopausal for less than 1 year (FSH levels of <=33.4 IU/L) or
receiving hormone replacement therapy (HRT).
3. Subjects with history of allergic, idiosyncratic or hypersensitivity
reactions to fluvoxamine, itraconazole or to any component of MEN1611 and
fluvoxamine and itraconazole formulations.
4. History or clinical evidence of any illness that might pose a risk to the
subject or interfere with the study procedures or the integrity of the study or
interfere with interpretation of data. In particular history or clinical
manifestations of metabolic (including type 1 and 2 diabetes), hepatic, renal,
haematological, pulmonary, cardiovascular, endocrine, gastrointestinal,
urological, neurological (including convulsive disorders), major psychiatric
disorders (including mood disorders and obsessive-compulsive disorders),
chronic skin conditions, chronic eye disorders (except for myopia,
hypermetropia and astigmatism) or cancer.
5. History of risk factors for torsades de pointes, including unexplained
syncope, known long QT syndrome, heart failure, myocardial infarction, angina.
Subjects will also be excluded if there is a family history of long QT syndrome
or Brugada syndrome or unexplained sudden death.
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 |
|---|---|
| EudraCT | EUCTR2022-001188-29-NL |
| CCMO | NL81096.056.22 |