In this study, we will evaluate a possible interaction between IMU-935 and midazolam. We will do this by investigating the effect of IMU-935 on how quickly and to what extent midazolam is absorbed, transported, and eliminated from the body. In…
ID
Source
Brief title
Condition
- Other condition
- Autoimmune disorders
- Prostatic disorders (excl infections and inflammations)
Synonym
Health condition
Chronic inflammatory diseases
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To assess the effect of multiple doses of IMU-935 on the PK of midazolam and
1*-hydroxymidazolam
after a single oral dose of midazolam when co-administered in healthy male and
female subjects.
Secondary outcome
- To assess the PK of IMU-935.
- To assess safety and tolerability of a single oral dose of midazolam alone
and in combination with steady-state IMU-935.
- To assess safety and tolerability of multiple oral doses of IMU-935.
Background summary
IMU-935 is a new compound that may potentially be used for the treatment of
psoriasis, Guillain-Barré syndrome and prostate cancer. Animal studies have
shown that IMU-935 works by reducing mediators responsible for localized tissue
reactions which contribute to these diseases.
In this study, the effect of IMU-935 on the existing medication midazolam will
be evaluated. Midazolam is a substance that is acted upon by particular liver
enzymes and transporters. Based on earlier experiments, IMU-935 may impact the
activity of these enzymes and transporters and as such may influence the
presence of midazolam in the body when given simultaneously.
Midazolam is a short-acting sedative used prior to a medical examination or
procedure. The dose level of midazolam used in the current study is far below
the marketed dose levels.
Study objective
In this study, we will evaluate a possible interaction between IMU-935 and
midazolam. We will do this by investigating the effect of IMU-935 on how
quickly and to what extent midazolam is absorbed, transported, and eliminated
from the body. In addition, we will investigate the pharmacokinetics of
IMU-935. Both these compounds will be administered in this study.
We will also investigate the safety and tolerability of both compounds and in
combination when it is used by healthy participants.
When we use the term study compound in this document, we mean IMU-935 or
midazolam.
IMU-935 has been used by humans before. In addition, it has been extensively
tested in the laboratory and on animals. Midazolam is no new compound; it is an
approved drug and already available on the market.
Study design
For the study it is necessary that the volunteer stays in the research center
for 4 periods, 1 period of 3 days (2 nights), 2 periods of 2 days (1 night) and
1 period of 6 days (5 nights).
Day 1 is the (first) day that the volunteer receives the study compound
(midazolam). The volunteer is expected at the research center the day before
the day of (first) administration of the study compound. The volunteer will
leave the research center on Day 2 of the study. The entry of Period 2 is on
Day 4 and the departure will take place on Day 5. The third entry is on Day 9
after which the volunteer leaves the research center on Day 10. The fourth
entry will take place on Day 15 and the volunteer will leave the research
center on Day 20.
Below is an overview of the days the volunteer stays at the research center, or
when they visit the research center:
- Screening
Day -21 to Day 2
- Period 1
Arrival: Day -1
Departure: Day 2
- Period 2
Arrival: Day 4
Departure: Day 5
- Period 3
Arrival: Day 9
Departure: Day 10
- Period 4
Arrival: Day 15
Departure: Day 20
- Follow-up
Between Day 27 and Day 34
The volunteer will receive midazolam as a drink containing 1 mg in the morning
of Day 1 and Day 16 under fasted conditions. The administration of the drink is
done with a syringe without a needle into the mouth, after which the study
compound can be swallowed. After taking the drink, the volunteer has to drink
another 240 milliliters (mL) of tap water. From Day 3 through Day 15 twice
daily (morning and evening) doses of IMU-935 as oral 150 mg capsules will be
taken with 240 mL of tap water and the volunteer will self-administer most of
these doses at home. IMU-935 should be taken at least 1 hour before or 1 hour
after meals. The volunteer will receive instructions for home dosing and a
diary in which they need to record the time of each dose of IMU-935 and note
details related to their health. The volunteer will be reminded daily not to
forget to take the study compound by telephone or text message. On Days 2, 5
and 10 the doses of IMU-935 will be given to the volunteer to be taken at home.
On Day 16 both midazolam and IMU-935 will be given in the research center in
the morning without breakfast.
During the first 4 hours after each administration of midazolam 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.
One of the investigators will inspect the hands and mouth of the volunteer
after the study compound intake while they are in the research center. This it
to check if the volunteer has taken the study compound.
Intervention
The planned doses are:
- Midazolam 1mg as a drink:
On day 1 once a day
On day 16 once a day
- IMU-935 150 mg as a capsule:
On days 3-15* Twice daily
On day 16 once a day
* The morning dose on Day 4, Day 9, and Day 15 will be taken at home, while the
evening dose on these days will be taken in the research center. The evening
dose on Days 5 and 10 will be taken at home, while the morning dose on these
days will be taken in the research center.
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 154 mL 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.
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.
Lochhamer Schlag 21
Graefelfing 82166
DE
Lochhamer Schlag 21
Graefelfing 82166
DE
Listed location countries
Age
Inclusion criteria
1. Sex : male or female of nonchildbearing potential
2. Age : 18 to 65 years, inclusive, at screening
3. Body mass index : 18.0 to 32.0 kg/m2, inclusive, at screening
4. Weight : >=55 kg at screening
5. Status : healthy subjects per discretion of the Investigator
6. Female subjects must be of nonchildbearing potential (either surgically
sterilized or
physiologically incapable of becoming pregnant, or at least 1 year
postmenopausal
[amenorrhea duration of 12 consecutive months]) and have a negative serum
pregnancy test at screening and a negative urine pregnancy test at each
admission
to the clinical research center.
7. Male subjects, if not surgically sterilized, must agree to use adequate
contraception and not donate sperm from first admission to the clinical
research center until 90 days after the follow-up visit. Adequate contraception
for the male subject (and his female partner, if she is of
childbearing potential) is defined as having his female partner using hormonal
contraceptives or an intrauterine device combined with the use of a condom by
the male subject for any sexual activity
Total abstinence, in accordance with the lifestyle of the subject, is also
acceptable.
8. All prescribed medication must have been stopped at least 30 days prior to
first
admission to the clinical research center.
9. All over-the-counter medication, vitamin preparations and other food
supplements,
or herbal medications (eg, St. John*s wort) must have been stopped at least
14 days prior to first admission to the clinical research center. An exception
is made
for paracetamol, which is allowed up to admission to the clinical research
center.
10. Ability and willingness to abstain from alcohol from 48 hours (2 days)
prior to
screening, each admission to the clinical research center, and follow-up, and
during
the stays in the clinical research center.
Further criteria apply, see protocol.
Exclusion criteria
1. Previous participation in the current study.
2. Employee of PRA or the Sponsor.
3. History of relevant drug and/or food allergies.
4. Patients with a history of acute angle-closure glaucoma or untreated
open-angle
glaucoma.
5. Using tobacco products within 60 days prior to the first drug administration.
6. History of alcohol abuse or drug addiction (including soft drugs like
cannabis
products).
7. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines
[including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic
antidepressants, cotinine, and alcohol) at screening or at one of the
admissions to
the clinical research center.
8. Average intake of more than 24 units of alcohol per week (1 unit of alcohol
equals
approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits).
9. Estimated glomerular filtration rate calculated by the Chronic Kidney Disease
Epidemiology Collaboration creatinine equation <60 mL/min/1.73m2.
10. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus
(HCV)
antibodies, or HIV 1 and 2 antibodies.
Further criteria apply, see protocol.
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 | EUCTR2021-005902-91-NL |
| CCMO | NL80022.056.21 |