The purpose of this study is to investigate how safe the new compound GDC-8264 is and how well it is tolerated when it is administered to healthy volunteers. GDC-8264 has not been administered to humans before. It has been previously tested in the…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The safety objective for this study is to evaluate the safety and tolerability
of single and multiple doses of GDC 8264 compared with placebo in healthy
subjects
Secondary outcome
To characterize the pharmacokinetics of GDC 8264.
Background summary
GDC-8264 is a new compound that may potentially be used for the treatment of
inflammatory bowel disease (IBD). IBD includes two main conditions: ulcerative
colitis and Crohn*s disease. These diseases are characterized by chronic
inflammation and increased cell death in parts of the intestines. The
gastrointestinal tract can therefore not work normally anymore. Patients who
suffer from IBD thus show symptoms such as abdominal pain, diarrhea and a
reduced appetite. Many of these patients require hospitalization and surgery.
In the Netherlands approximately 1 in 200 people suffer from this disease.
GDC-8264 works by preventing cell death and inflammation by blocking RIP1
kinase from performing its action. This protein plays an important role in
regulating cell death and blocking it can result in reduced inflammation.
Study objective
The purpose of this study is to investigate how safe the new compound GDC-8264
is and how well it is tolerated when it is administered to healthy volunteers.
GDC-8264 has not been administered to humans before. It has been previously
tested in the laboratory and on animals. GDC-8264 will be tested at various
dose levels. It will also be investigated how quickly and to what extent
GDC-8264 is absorbed and eliminated from the body. The effects of GDC-8264 will
be compared to the effects of a placebo.
DDI:
In at least one group of the MAD part, we will investigate whether GDC-8264 can
influence how other compounds are handled by the body. This is called a
drug-drug interaction (DDI) study. For this purpose, GDC-8264 will be given
together with midazolam. Midazolam is not a new medication; it has been used in
clinical practice since the mid-1980s. It is currently approved to treat sleep
disorders and is sometimes used during anesthesia. In this study midazolam will
be used as a model to measure the activity of CYP3A4, an enzyme that helps to
break down chemicals in the body. First, we will examine how fast your body
breaks down midazolam. Second, we will measure to what extent GDC-8264
influences this break down process.
Study design
SAD:
The study will consist of 1 period during which the subjects will stay in the
research center for 6 days (5 nights). This will be followed by 1 day during
which they will visit the research center for a short visit.
FE:
The study will consist of 3 periods during each the subjects will stay in the
research center for 6 days (5 nights). They can return home in between these
periods. This will be followed by 1 day during which they will visit the
research center for a short visit.
MAD:
The study will consist of 1 period during which the subjects will stay in the
research center for up to 19 days (18 nights). This will be followed by 2 days
during which they will visit the research center for a short visit.
DDI:
The study will consist of 1 period during which the subjects will stay in the
research center for up to 15 days (14 nights). This will be followed by 2 days
during which they will visit the research center for a short visit.
Intervention
The subjects will receive a single or multiple doses of GDC-8264 or placebo as
tablets orally with 240 milliliters (mL) of water, or as a suspension. The
starting dose is 5 mg.
Midazolam is given through a syringe without a needle in the mouth, after which
it can be swallowed. One also gets 200 ml of water to rinse the mouth and to
swallow. Midazolam is given after 8 hours of fasting. In addition, fasting
continues for up to 4 hours after ingestion. Two single doses of midazolam of 5
mg each are given: once on Day 1 and once on Day 10.
Study burden and risks
As GDC-8264 will be administered to humans for the first time in this study,
side effects of GDC-8264 in humans have not been reported to date. GDC-8264 has
been studied extensively in the laboratory and in animals. The compound was
generally well tolerated and did not result in significant changes in
measurements of blood pressure, heart rate, heart tracings, behavior and
respiratory function. Drawing blood and/or insertion of the indwelling cannula
may be painful or cause some bruising.
Building 686
Basel 4070
CH
Building 686
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
- Age 18 to 55 years, inclusive
- Body mass index between 18 and 30 kg/m2, inclusive
- Ability to comply with the study protocol, in the investigator's judgment
- Expressed willingness to participate in the entire study
- For women of childbearing potential: use contraception as described in
protocol.
For men: use a condom, and agreement to refrain from donating sperm, as
defined in protocol
- For subjects screened at PRA Health Sciences: meeting of site-specific
COVID-19 criteria
Exclusion criteria
- Pregnant or breastfeeding, or intending to become pregnant during the study
or within 90 days or 5 half-lives of GDC-8264, whichever is longer, after the
final dose of study drug
- Treatment with investigational therapy within 90 days prior to initiation of
study drug
- Participation in more than four other drug studies in the 12 months prior to
drug administration in the current study
- Subjects who have been previously enrolled in this study
- Study site employees or immediate family members of a study site or Sponsor
employee
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 | EUCTR2019-002613-19-NL |
| CCMO | NL72106.056.19 |