The purpose of this study is to investigate how safe the compound LY3526318 is and how well it is tolerated when it is administered to healthy participants. It will also be investigated how quickly and to what extent LY3526318 is absorbed and…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Chronische Pijn
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A: To determine the pharmacokinetics of LY3526318 after a single oral dose
administration
Part B: To determine the pharmacokinetics of LY3526318 after multiple oral dose
administrations
Secondary outcome
Part A: To estimate the safety and tolerability of LY3526318 after single (Part
A) oral administration to healthy participants
To evaluate the effect of a meal on the pharmacokinetics of LY3526318 in fed
versus fasted conditions
Part B: To estimate the safety and tolerability of LY3526318 after multiple
oral administrations to healthy participants
Background summary
In this study, LY3526318 is being researched as a potential treatment for
chronic pain. The study compound is not registered in The Netherlands as a
medication. This means that the study compound is still in development.
Current treatment options for chronic pain include so-called non
steroidal-anti-inflammatory drugs (NSAIDs) and opioid-based therapeutics.
Disadvantages of these treatment options are that NSAIDs are not completely
effective as judged by many patients and that opioids are addictive and may
have unwanted effects on brain functioning.
LY3526318 has a different working mechanism by inhibiting a protein called
*transient receptor protein ankyrin 1* (TRPA1). This TRPA1-protein is present
on nerve cells that transmit painful stimuli.
Study objective
The purpose of this study is to investigate how safe the compound LY3526318 is
and how well it is tolerated when it is administered to healthy participants.
It will also be investigated how quickly and to what extent LY3526318 is
absorbed and eliminated form the body (this is called pharmacokinetics).
LY3526318 has been administered to humans before and will be tested at various
dose levels.
The effects of LY3526318 will be compared to the effects of a placebo. A
placebo is a medicine without any active ingredient. Please note that when the
term *study compound* is used in this document, this can refer to LY3526318,
placebo, or both.
This study will be performed in 16 healthy male and female participants. The
study consists of 2 parts (A and B) where the volunteer can only participate in
1 part. In Part A maximal 4 doses of LY3526318 will be administered, between
each dose will be at least 14 days (2 weeks). In Part B multiple doses of
LY3526318 will be administered once daily for up to 5 days.
Study design
Part A: LY3526318 or placebo is given as capsule (s) by mouth with 240
milliliters (ml) of water once per period. After taking the research drug, one
of the researchers will inspect the hands and mouth.
A maximum of 4 doses of the study drug can be received. Depending on the
results in the (previous) period (s), the next step will be determined. Up to 3
dose levels will be studied after fasting (fasting at least 8 hours prior to
and at least 4 hours after dosing). Up to 2 of these dose levels that were
studied after fasting may also be studied after food (a high-fat meal 30
minutes prior to dosing). The options are:
• 3 times without breakfast after an overnight fast and 1 time with a high-fat
breakfast
• 2 times without breakfast after an overnight fast and 2 times after a
high-fat breakfast
• 3 times without breakfast after an overnight fast
• 2 times without breakfast after an overnight fast and 1 time after a high-fat
breakfast
• 2 times without breakfast after an overnight fast
The high-fat breakfast should be started right on time and eaten whole within
20 minutes.
Part A consists of 4 periods during which participants will stay in the
research center for 4 days (3 nights) for each period. Each period is followed
by 2 short visits, the time of arrival at the study center will be told during
the stay in the clinic. Between 4 and 6 days after the last short visit there
will also be a follow-up visit. Some participants will be scheduled for all 4
periods and some will be scheduled for only 1 or 2 periods. Between each period
there will be at least 1 week. Day 1 is the day the study drug is administered.
It is expected at the study center at 2:00 pm in the afternoon prior to study
drug administration day. The entry time can be adjusted. If this happens, they
will be informed in advance. The research center is left on Day 3 of the
examination.
Part B: LY3526318 or placebo is given as capsule (s) by mouth with 240
milliliters (ml) of water once daily for 5 days. After taking the research
drug, one of the researchers will inspect the hands and mouth.
Participants receive daily doses for up to 5 days, without breakfast after an
overnight fast or after eating a high-fat, fixed-composition breakfast, or
either option (fast or after a high-fat breakfast) on different days.
The high-fat breakfast should be started right on time and eaten whole within
20 minutes.
The actual research consists of 1 period during which one will stay in the
research center for 9 days (8 nights). Day 1 through Day 5 are the days on
which the study drug is administered. It is expected at 2:00 PM in the
afternoon prior to the day of the first study drug administration at the study
center. The entry time can be adjusted. If this happens, they will be informed
in advance. The research center is left on Day 8 of the examination.
Intervention
Part A:
Period 1 Day 1 LY3526318 100 mg or placebo once Fasted
Period 2 Day 1 LY3526318 250 mg or placebo once Fasted
Period 3 Day 1 LY3526318 XX# mg or placebo once Fasted or after high fat
breakfast
Period 4 Day 1 LY3526318 XX# mg or placebo once Fasted or after high-fat
breakfast
#: The dose will be based on the results of previous period(s).
Up to 2 of the doses will be administrated after a high-fat breakfast. This
will be based on the results of previous period(s).
Part B:
Days 1 to 5 LY3526318 XX# mg or placebo once daily Fasted or after high-fat
breakfast
Study burden and risks
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, we will take about 170 milliliters (mL) of blood. This amount does
not cause any problems in adults.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
The high-fat breakfast is a big breakfast consisting of 2 fried eggs, fried
potatoes and bacon. The volunteers must consume the breakfast entirely within
20 minutes. Particularly for light eaters, it can be difficult to consume the
entire breakfast, and it might cause some discomfort if they are not sed to a
large breakfast.
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 the volunteer to gag. When the sample is taken from the back of
the nose, they may experience a stinging sensation and the eyes may become
watery.
McCarty Street 1
Indiana 46285
US
McCarty Street 1
Indiana 46285
US
Listed location countries
Age
Inclusion criteria
1. Aged 18 to 65 years, inclusive.
2. Healthy male participants, as determined through medical history and physical
examination.
a. A nonvasectomized, male participant must agree to use a condom or abstain
from
sexual intercourse from start of dosing until 105 days beyond the last dose of
study
intervention.
b. No restrictions are required for a vasectomized male provided his vasectomy
has been
performed at least 4 months or prior to screening. A male who has been
vasectomized
*4 months prior to screening must follow the same restrictions as a
nonvasectomized
male
c. Must agree not to donate sperm from start of dosing until 105 days beyond
the last
dose of study intervention.
3. Healthy female participants of child-bearing potential who have a fertile
male sexual
partner must be willing and able to practice effective contraception from
admission to
105 days beyond the last dose of study intervention. Sexually active
participants must use
a combination of 2 of the following methods of contraception, including at
least 1 socalled
*barrier* method:
a. hormonal contraceptives (oral, transdermal patches, vaginal, or injectable)
b. intrauterine device with or without hormones
c. condom, diaphragm, or cervical cap (*barrier* method), and
d. sexual abstinence.
Contraceptive requirements do not apply for participants who are exclusively in
a same-sex
relationship. Additional guidance is provided in Section 10.4, Appendix 4.
4. Have a body mass index of 18 to 32 kg/m2, inclusive.
5. Are reliable and willing to make themselves available for the duration of
the study and
are willing to follow CRU-specific study procedures.
6. Have clinical laboratory test results within normal reference range for the
population or
CRU, or results with acceptable deviations that are judged not clinically
significant by the
investigator.
7. Capable of giving signed informed consent as described in Section 10.1.2,
Appendix 1,
which includes compliance with the requirements and restrictions listed in the
informed
consent form (ICF) and in this protocol.
Exclusion criteria
1. Have a history or presence of medical illness including, but not limited to,
any
cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or
neurological
disease, convulsions, or any clinically significant laboratory abnormality
that, in the
judgment of the investigator, indicate a medical problem that would preclude
study
participation.
2. Any abnormalities identified following a physical examination of the
participant that, in
the opinion of the investigator, would jeopardize the safety of the participant
or interfere
with study conduct if they took part in the study.
3. Positive SARS-CoV-2 virus nasopharyngeal polymerase chain reaction test at
Day -1.
4. Contact with SARS-CoV-2-positive or COVID-19 patient within the last 14 days
prior to
admission to the CRU.
Design
Recruitment
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 | EUCTR2020-004290-46-NL |
| CCMO | NL75806.056.20 |