In this study, we will investigate what the effect of the new compound emvododstat is on how quickly and to what extent 2 approved medications (dextromethorphan in Part 1 and rosuvastatin in Part 2) are absorbed, transported, and eliminated from the…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endpoints for assessment of emvododstat as a perpetrator when administered with
a CYP2D6 substrate (dextromethorphan) and BCRP substrate (rosuvastatin):
PK Parameters:
- Dextromethorphan and dextrophan: AUC0-t, AUC0-inf, Cmax
- Rosuvastatin: AUC0-t, AUC0-inf, Cmax
Secondary outcome
PK Parameters:
- Dextromethorphan and dextrophan: T1/2, Tmax, apparent clearance (CL/F), and
terminal elimination rate constant (kel)
- Rosuvastatin: T1/2, Tmax, kel, CL/F
Endpoints for safety and tolerability assessment when emvododstat is
administered in combination with a CYP2D6 (dextromethorphan) and BCRP
(rosuvastatin) substrates:
- Adverse events
- Chemistry and hematology laboratory panels
- 12 lead ECGs
- Vital signs
- Physical examinations
Background summary
Emvododstat is a new compound that may potentially be used for the treatment of
acute leukemia. Acute leukemia is a rapidly progressing cancer that starts in
blood-forming tissue such as the bone marrow, and causes large numbers of
abnormal blood cells to be produced and enter the blood stream.
Emvododstat inhibits a certain enzyme (the enzyme called dihydroorotate
dehydrogenase) that plays a role in the production of rapidly dividing cells,
such as leukemia cells. Inhibition of this enzyme stops the cell cycle and in
the end may results in cell death of rapidly dividing cells.
Emvododstat may also inhibit the replication of viral cells. As such,
emvododstat may also potentially be used for the treatment of COVID 19, the
disease that is caused by the coronavirus (officially SARS CoV 2). COVID-19 is
an infectious disease that causes respiratory tract infections and is spread
worldwide.
Dextromethorphan reduces the tendency to cough and is used for tickling cough./
Rosuvastatin lowers cholesterol and other fats in your blood. It also reduces
clogging of our arteries.
Study objective
In this study, we will investigate what the effect of the new compound
emvododstat is on how quickly and to what extent 2 approved medications
(dextromethorphan in Part 1 and rosuvastatin in Part 2) are absorbed,
transported, and eliminated from the body. To be able to investigate this
possible interaction, the volunteer will be given both emvododstat and
dextromethorphan (in Part 1) or emvododstat and rosuvastatin (in Part 2).
We also investigate how safe emvododstat is and how well it is tolerated when
it is used in combination with dextromethorphan (in Part 1) and rosuvastatin
(in Part 2) by healthy participants.
For this study, we are looking for 36 healthy male and female participants.
Each part will consist of 18 subjects.
Emvododstat has been used by humans before. In addition, it has been
extensively tested in the laboratory and on animals.
Dextromethorphan/Rosuvastatin is no new compound; it is an approved drug and
already being used in various doses by patients.
When we use the term study compound in this document, we mean emvododstat,
dextromethorphan, rosuvastatin, or a combination of these compounds.
Study design
Part 1:
For the study, it is necessary that the volunteer stays in the research center
for 1 period of 8 days (7 nights)/ . Furthermore, we will call the volunteer
for a follow-up approximately 2 weeks after discharge (Day 21) and
approximately 30 days after the last administration of the study compound. On
Day 29 and approximately 180 days after the last administration of the study
compound, women of childbearing potential will need to perform a pregnancy test
at home.
The volunteer will be given emvododstat and dextromethorphan as oral tablets
with 240 milliliters (mL) of water.
Part 2:
For the study, it is necessary that the volunteer stays in the research center
for 1 period of 16 days (15 nights). Furthermore, we will call the volunteer
for a follow-up approximately 2 weeks after discharge (Day 29) and
approximately 30 days after the last administration of the study compound. On
Day 29 and approximately 180 days after the last administration of the study
compound, women of childbearing potential will need to perform a pregnancy test
at home.
The volunteer will be given emvododstat and rosuvastatin as oral tablets with
240 milliliters (mL) of water.
Intervention
Part 1:
Day | Study compound | How much | How often
1 | Dextromethorphan | 30 mg | Once
2 to 4| - | - | -
5 | Emvododstat | 250 mg | Once
| Dextromethorphan | 30 mg | Once
Part 2:
Day | Study compound | How much | How often
1 | Rosuvastatin | 20 mg | Once
2 to 7 | - | - | -
8 to 11 | Emvododstat | 100 mg | Twice daily
12 | Emvododstat | 100 mg | Twice
| Rosuvastatin | 20 mg | Once
13 to 14| Emvododstat | 100 mg | Twice daily
Study burden and risks
Blood draw
Drawing blood may be painful or cause some bruising. On the days of
administration of dextromethorphan/rosuvastatin, blood will be sampled very
frequently using an indwelling cannula (a tube in a vein in the arm ) to
determine the course of the concentration of dextromethorphan/rosuvastatin in
the blood over time. The use of the indwelling cannula can sometimes lead to
inflammation, swelling, hardening of the vein, blood clotting, and/or bruising
around the puncture site. In some individuals, a blood draw can sometimes cause
pallor, nausea, sweating, low heart rate, and/or a drop in blood pressure with
dizziness or fainting.
In total, we will take about 200 mL of blood from the volunteer. 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
may be more than the amount indicated above.
Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed on
the volunteer's arms, chest, and legs. Prolonged use of these electrodes can
cause skin irritation (rash and itching).
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 volunteer's
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 volunteer's throat may cause him to gag. When the sample is
taken from the back of his nose, he may experience a stinging sensation and his
eyes may become watery.
Corporate Court 100
South Plainfield 07080
US
Corporate Court 100
South Plainfield 07080
US
Listed location countries
Age
Inclusion criteria
1. Healthy adult, non-smokers (no use of tobacco products within 6 months prior
to Screening), >=18 and <=65 years of age.
2. Body mass index >18.0 and <30.0 kg/m2 and body weight >=50.0 kg and <=110.0 kg.
3. Ability to swallow tablets
4. Women of child-bearing potential (as defined in (CTFG 2014)) must have a
negative pregnancy test at Screening and agree to abstinence or the use at
least one of the following highly effective forms of contraception (with a
failure rate of <1% per year when used consistently and correctly) in addition
to barrier method for their sexual partner. Contraception or abstinence must be
continued for the duration of the study following discharge from the hospital,
and for up to 180 days after the last dose of study drug:
- Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation:
- Oral
- Intravaginal
- Transdermal
- Progestogen-only hormonal contraception associated with inhibition of
ovulation:
- Oral
- Injectable
- Implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Vasectomized partner with confirmed azoospermia
All females will be considered of child-bearing potential unless they are
postmenopausal (at least 12 months consecutive amenorrhea in the appropriate
age group without other known or suspected cause) or have been sterilized
surgically (eg, bilateral tubal ligation, hysterectomy, bilateral oophorectomy).
5. Sexually active and fertile males must use a condom during intercourse while
taking study drug and for 90 days after stopping study drug and should not
father a child in this period. A condom is required to be use by vasectomized
men in order to prevent delivery of the drug via seminal fluid.
Further criteria apply
Exclusion criteria
1. For Part 1 (CYP2D6 substrate), subjects who are poor metabolizers of CYP2D6
isoenzymes are excluded.
2. Pregnant or lactating subjects or those sexually active subjects who are
unwilling to comply with proper birth control methods; females of child-bearing
potential must have a negative pregnancy test at Screening and during the
Baseline Visit.
3. Aspartate aminotransferase or alanine aminotransferase above the upper limit
of normal (ULN) at the time of Screening or Baseline. Values above ULN may be
allowed if considered not clinically significant at the discretion of the
Investigator.
4. International normalized ratio >=1.5×ULN at time of Screening or Baseline or
clinically significant bleeding, as determined by the Investigator.
5. Serum creatinine >=1.5×ULN at time of Screening or Baseline.
Further criteria apply
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 | EUCTR2021-004626-29-NL |
| CCMO | NL78966.056.21 |