The main purpose of this study is to investigate the effect of ASTX660 on how quickly and to what extent quinidine and fexofenadine are absorbed, distributed, broken down and eliminated from the body. Quinidine and fexofenadine have been chosen…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To determine the effect of P-glycoprotein (P-gp) inhibition by quinidine on
pharmacokinetics (PK) of ASTX660
- To determine the effect of P-gp inhibition by ASTX660 on PK of fexofenadine
Secondary outcome
- To determine the safety and tolerability of ASTX660 following oral
administration alone or in combination with quinidine, a P-gp probe inhibitor;
or with fexofenadine, a P-gp probe substrate
Background summary
ASTX660 is a new compound that may potentially be used for the treatment of
patients with advanced solid tumors, lymphoma, and acute myeloid leukemia (AML,
cancer of blood and bone marrow) and for whom standard life prolonging measures
are not available.
Study objective
The main purpose of this study is to investigate the effect of ASTX660 on how
quickly and to what extent quinidine and fexofenadine are absorbed,
distributed, broken down and eliminated from the body.
Quinidine and fexofenadine have been chosen because they are known to interact
with a certain enzyme in the liver. By looking at the effect of ASTX660 on
these agents, something can also be said about whether ASTX660 has an influence
on this enzyme. This is important to know when ASTX660 is given in the future
along with agents that are also interacting with this enzyme.
The safety of ASTX660 as well as how it is tolerated in the presence of
quinidine and fexofenadine will also be investigated.
We also look at the effect of the genetic information on the body*s response to
ASTX660. This part of the study is mandatory.
ASTX660 has been used by humans before. In addition, it has been extensively
tested in the laboratory and on animals. Quinidine and fexofenadine are already
available on the market in several dosages and formulations for the treatment
of cardiac arrythmias (quindine) and allergies such as hay fever
(fexofenadine).
Study design
For the study it is necessary that the volunteers stays in the research center
for 2 periods of 4 days (3 nights). There will be an in between period of at
least 7 days between the administration of the study compound in Period 1 and
the administration of the study compound in Period 2.
Day 1 is the day when the volunteer receives the study compound. In each
period, the volunteer is expected at the research center the day before the day
of first administration of the study compound. The volunteer has to be at the
research center at 14:00 hrs in the afternoon. The volunteer will leave the
research center on Day 3 of each period.
Intervention
During the study the volunteer will receive ASTX660, quinidine (Group 1 only),
or fexofenadine (Group 2 only) after an overnight fast (at least 10 hours).
The volunteer will be given ASTX660, quinidine (Group 1 only), or fexofenadine
(Group 2 only) as oral capsules (ASTX660) or tablets (quinidine or
fexofenadine) with 240 milliliters (mL) of (tap) water.
During each treatment period the volunteer will continue fasting until 4 hours
after administration of the study compound. Then he/she will receive lunch.
During fasting the volunteer is allowed to drink water with the exception of 2
hours prior to until 1 hour after administration of the study compound.
During the first 4 hours after administration of the study compound the
volunteer will not be allowed to lie down (except when instructed to do so by
one of the investigators), as this may influence the uptake of the study
compound.
The study consists of 2 treatment periods. In Group 1, the volunteer will
receive ASTX660 (120 mg) alone on the first day of Treatment Period 1 and
ASTX660 (120 mg) and quinidine (600 mg) at the same time on the first day of
Treatment Period 2. In Group 2, the volunteer will receive fexofenadine (120
mg) alone on the first day of Treatment Period 1 and fexofenadine (120 mg) with
ASTX660 (180 mg) at the same time on the first day of Treatment Period 2.
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 270 milliliters (mL) of blood from the volunteers.
This amount does not cause any problems in adults. To compare: a blood donation
involves 500 mL of blood being taken 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
will be more than the amount indicated above.
Heart tracing
To make a heart tracing, electrodes will be placed on the arms, chest and legs.
In Group 1, heart rate will also be monitored continuously with telemetry for a
longer period, for which electrodes will be placed on the chest and abdomen.
Prolonged use of these electrodes can cause skin irritation.
Fasting
If the volunteer 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 the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.
Rosewood Drive, Suite 200 4420
Pleasanton CA 94588
US
Rosewood Drive, Suite 200 4420
Pleasanton CA 94588
US
Listed location countries
Age
Inclusion criteria
1. Sex assigned at birth : male or female; females of nonchildbearing
potential, or postmenopausal.
2. Age : 18 to 65 years, inclusive, at screening.
3. Body mass index (BMI) : 18.0 to 32.0 kg/m2, inclusive, at screening.
4. Weight : >=50 kg.
5. Status : healthy subjects.
Exclusion criteria
1. Employee of PRA or the Sponsor.
2. History of relevant drug and/or food allergies.
3. History of alcohol abuse or drug addiction (including soft drugs like
cannabis products) within 2 years prior to screening in the current study.
4. History or presence of atrioventricular block (any degree) or sick sinus
syndrome.
5. Subjects with increased cardiac risk evaluation based on the following
criteria:
• Smoking (no more than 2 packs of cigarettes) in the last 6 months prior to
admission, including use of nicotine-containing products (eg, snuff, nicotine
patch, nicotine chewing gum, mock cigarettes, e-cigarettes, or inhalers), or
positive cotinine test at screening (ie, cotinine value >500 ng/mL will be
excluded).
• Subjects with first-degree family history of ischemic cardiac event at a
young age (male <55; female <65 years).
• Subjects with family history of arrhythmia, sudden unexplained death at a
young age (before 40 years) in a first-degree relative, or long QT syndrome,
Torsades de Pointes (TdP), or a personal history of repeated or frequent
syncope or vasovagal episodes, or treatment for high blood pressure.
• History or presence of resuscitated arrest possibily due to TdP;
hypertension, angina, or severe peripheral arterial circulatory disorders.
• History or presence of risk factors for TdP (eg, congenital deafness, heart
failure, cardiomyopathy).
• History or presence of myocardial infarction, pulmonary congestion, cardiac
arrhythmia, or prolonged QT interval, or conduction abnormalities.
• History or presence of concomitant medications-induced QTc prolongation
within 30 days prior to screening.
• History or presence of hypokalemia, hypomagnesemia, or hypocalcemia.
See the protocol for the complete overview
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 | EUCTR2021-003459-40-NL |
| CCMO | NL78420.056.21 |